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1. Determination of the target of monoclonal immunoglobulins: a novel diagnostic tool for individualized MGUS therapy, and prevention and therapy of smoldering and multiple myeloma

Author

Sylvie Hermouet, Edith Bigot-Corbel, and Jean Harb

Subjects
monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), multiple myeloma (MM), monoclonal immunoglobulin, infectious pathogens, glucosylsphingosine (GlcSph), Immunologic diseases. Allergy, RC581-607
Abstract

Subsets of patients diagnosed with a monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM) or multiple myeloma (MM), present with a monoclonal immunoglobulin (Ig) specific for an infectious pathogen, including hepatitis C and B viruses (HCV, HBV), Helicobacter pylori and several Herpesviruses. Such cases are likely initiated by infection, since in the context of HCV- or HBV-infected patients, antiviral therapy can lead to the disappearance of antigenic stimulation, control of clonal plasma cells, and reduced or suppressed monoclonal Ig production. Complete remission has been obtained with anti-HCV therapy in refractory MM with a HCV-specific monoclonal Ig, and antiviral treatments significantly improved the probability of survival of MM patients infected with HCV or HBV prior to the diagnosis of MM. Monoclonal Igs may also target glucolipids, particularly glucosylsphingosine (GlcSph), and GlcSph-reducing therapy can lead to complete remission in SMM and MM patients presenting with a GlcSph-specific monoclonal Ig. The present review describes the importance of determining the target of the monoclonal Ig of MGUS, SMM and MM patients, and discusses the efficacy of target-reducing treatments in the management of MGUS, SMM and MM cases who present with a monoclonal Ig reactive against a treatable infectious pathogen or GlcSph.

Published
2023
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2. Impact of viral hepatitis therapy in multiple myeloma and other monoclonal gammopathies linked to hepatitis B or C viruses

Author

Alba Rodríguez-García, Nicolas Mennesson, Gema Hernandez-Ibarburu, María Luz Morales, Laurent Garderet, Lorine Bouchereau, Sophie Allain-Maillet, Eric Piver, Irene Marbán, David Rubio, Edith Bigot-Corbel, Joaquín Martínez-López, María Linares, and Sylvie Hermouet

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

Subsets of multiple myeloma (MM) and monoclonal gammopathies of undetermined significance (MGUS) present with a monoclonal immunoglobulin specific for hepatitis C virus (HCV), thus are presumably HCV-driven, and antiviral treatment can lead to the disappearance of antigen stimulation and improved control of clonal plasma cells. Here we studied the role of hepatitis B virus (HBV) in the pathogenesis of MGUS and MM in 45 HBV-infected patients with monoclonal gammopathy. We analyzed the specificity of recognition of the monoclonal immunoglobulin of these patients and validated the efficacy of antiviral treatment (AVT). For 18 of 45 (40%) HBV-infected patients, the target of the monoclonal immunoglobulin was identified: the most frequent target was HBV (n=11), followed by other infectious pathogens (n=6) and glucosylsphingosine (n=1). Two patients whose monoclonal immunoglobulin targeted HBV (HBx and HBcAg), implying that their gammopathy was HBV-driven, received AVT and the gammopathy did not progress. AVT efficacy was then investigated in a large cohort of HBV-infected MM patients (n=1367) who received or did not receive anti-HBV treatments and compared to a cohort of HCV-infected MM patients (n=1220). AVT significantly improved patient probability of overall survival (P=0.016 for the HBV-positive cohort, P=0.005 for the HCV-positive cohort). Altogether, MGUS and MM disease can be HBV- or HCV-driven in infected patients, and the study demonstrates the importance of AVT in such patients.

Published
2023
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3. Plasma apolipoprotein concentrations and incident diabetes in subjects with prediabetes

Author

Mikaël Croyal, Matthieu Wargny, Kevin Chemello, Chloé Chevalier, Valentin Blanchard, Edith Bigot-Corbel, Gilles Lambert, Cédric Le May, Samy Hadjadj, and Bertrand Cariou

Subjects
New-onset diabetes, Type 2 diabetes, Apolipoproteins, Apolipoprotein E, IT-Diab study, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Abstract Background The identification of circulating biomarkers associated with the risk of type 2 diabetes (T2D) is useful for improving the current prevention strategies in the most at-risk patients. Here, we aimed to investigate the association of plasma apolipoprotein concentrations in prediabetes subjects with the incidence of new-onset T2D during follow-up. Methods In the IT-DIAB prospective study, 307 participants with impaired fasting glucose levels (fasting plasma glucose [FPG]: 110–125 mg/dL) were followed yearly for 5 years. The onset of T2D was defined as a first FPG value ≥ 126 mg/dL during follow-up. Apolipoprotein (apo)A-I, A-II, A-IV, B100, C-I, C-II, C-III, C-IV, D, E, F, H, J, L1, M, and (a) plasma concentrations were determined by mass spectrometry. Correlations between apolipoproteins and metabolic parameters at baseline were assessed by Spearman’s coefficients. Kaplan–Meier curves were drawn using a ternary approach based on terciles and incident T2D. The association between plasma apolipoproteins concentrations and the incidence of T2D was determined using Cox proportional-hazards models. Results During a median follow-up of 5-year, 115 participants (37.5%) developed T2D. After adjustment for age, sex, body mass index, FPG, HbA1c, and statin use, the plasma levels of apoC-I, apoC-II, apoC-III, apoE, apoF, apoH, apoJ, and apoL1 were positively associated with a high risk for T2D. After further adjustment for plasma triglycerides, only apoE (1 SD natural-log-transformed hazard ratio: 1.28 [95% confidence interval: 1.06; 1.54]; p = 0.010), apoF (1.22 [1.01; 1.48]; p = 0.037), apoJ (1.24 [1.03; 1.49]; p = 0.024), and apoL1 (1.26 [1.05; 1.52]; p = 0.014) remained significantly associated with the onset of T2D. Kaplan–Meier survival curves also showed that the lower third of plasma apoE levels (

Published
2022
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4. Early recognition of cardiac surgery-associated acute kidney injury: lack of added value of TIMP2 IGFBP7 over short-term changes in creatinine (an observational pilot study)

Author

Karim Lakhal, Edith Bigot-Corbel, Emilie Sacchetto, Floris Chabrun, Thomas Senage, Lucile Figueres, Maxime Leroy, Arnaud Legrand, and Bertrand Rozec

Subjects
Acute kidney injury [MeSH], Insulin-like growth factor binding proteins/urine* [MeSH], Tissue inhibitor of Metalloproteinase-2/urine* [MeSH], Tissue inhibitor of Metalloproteinase-2 [MeSH], Creatinine/blood [MeSH], Lipocalins/metabolism* [MeSH], Anesthesiology, RD78.3-87.3
Abstract

Abstract Background For the detection of cardiac surgery-associated acute kidney injury (CS-AKI), the performance of urine tissue inhibitor of metalloproteinase 2 insulin-like growth factor-binding protein 7 (TIMP2 IGFBP7) has never been compared with that of very early changes in plasma creatinine (∆pCr). We hypothesized that, in the context of perioperative haemodilution, lack of postoperative decrease in pCr would be of honourable performance for the detection of CS-AKI. We therefore aimed at comparing these biomarkers and their kinetics (primary objective). As secondary objectives, we assessed plasma neutrophil gelatinase-associated lipocalin (pNGAL), cystatin C (pCysC) and urea (pUrea). We also determined the ability of these biomarkers to early discriminate persistent from transient CS-AKI. Methods Patients over 75 years-old undergoing aortic valve replacement with cardiopulmonary bypass (CPB) were included in this prospective observational study. Biomarkers were measured before/after CPB and at the sixth postoperative hour (H6). Results In 65 patients, CS-AKI occurred in 27 (42%). ∆pCr from post-CPB to H6 (∆pCrpostCPB-H6): outperformed TIMP2 IGFBP7 at H6 and its intra- or postoperative changes: area under the receiver operating characteristic curve (AUCROC) of 0.84 [95%CI:0.73–0.92] vs. ≤0.67 [95%CI:0.54–0.78], p ≤ 0.03. The AUCROC of pNGAL, pCysC and pUrea did not exceed 0.72 [95%CI:0.59–0.83]. Indexing biomarkers levels for blood or urine dilution did not improve their performance. Combining TIMP2 IGFBP7 and ∆pCrpostCPB-H6 was of no evident added value over considering ∆pCrpostCPB-H6 alone. For the early recognition of persistent CS-AKI, no biomarker outperformed ∆pCrpostCPB-H6 (AUCROC = 0.69 [95%CI:0.48–0.85]). Conclusions In this hypothesis-generating study mostly testing early detection of mild CS-AKI, there was no evident added value of the tested modern biomarkers over early minimal postoperative changes in pCr: despite the common perioperative hemodilution in the setting of cardiac surgery, if pCr failed to decline within the 6 h after CPB, the development of CS-AKI was likely. Confirmatory studies with more severe forms of CS-AKI are required.

Published
2021
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5. Atrophic Gastritis and Autoimmunity: Results from a Prospective, Multicenter Study

Author

Malgorzata Osmola, Caroline Hemont, Nicolas Chapelle, Marie-Anne Vibet, David Tougeron, Driffa Moussata, Dominique Lamarque, Edith Bigot-Corbel, Damien Masson, Justine Blin, Maxime Leroy, Regis Josien, Jean-François Mosnier, Jérôme Martin, and Tamara Matysiak-Budnik

Subjects
autoimmune gastritis, chronic atrophic gastritis, autoimmunity, gastric cancer, H. pylori, Medicine (General), R5-920
Abstract

Despite a global decrease, gastric cancer (GC) incidence appears to be increasing recently in young, particularly female, patients. The causal mechanism for this “new” type of GC is unknown, but a role for autoimmunity is suggested. A cascade of gastric precancerous lesions, beginning with chronic atrophic gastritis (CAG), precedes GC. To test the possible existence of autoimmunity in patients with CAG, we aimed to analyze the prevalence of several autoantibodies in patients with CAG as compared to control patients. Sera of 355 patients included in our previous prospective, multicenter study were tested for 19 autoantibodies (anti-nuclear antibodies, ANA, anti-parietal cell antibody, APCA, anti-intrinsic factor antibody, AIFA, and 16 myositis-associated antibodies). The results were compared between CAG patients (n = 154), including autoimmune gastritis patients (AIG, n = 45), non-autoimmune gastritis patients (NAIG, n = 109), and control patients (n = 201). ANA positivity was significantly higher in AIG than in NAIG or control patients (46.7%, 29%, and 27%, respectively, p = 0.04). Female gender was positively associated with ANA positivity (OR 0.51 (0.31–0.81), p = 0.005), while age and H. pylori infection status were not. Myositis-associated antibodies were found in 8.9% of AIG, 5.5% of NAIG, and 4.4% of control patients, without significant differences among the groups (p = 0.8). Higher APCA and AIFA positivity was confirmed in AIG, and was not associated with H. pylori infection, age, or gender in the multivariate analysis. ANA antibodies are significantly more prevalent in AIG than in control patients, but the clinical significance of this finding remains to be established. H. pylori infection does not affect autoantibody seropositivity (ANA, APCA, AIFA). The positivity of myositis-associated antibodies is not increased in patients with CAG as compared to control patients. Overall, our results do not support an overrepresentation of common autoantibodies in patients with CAG.

Published
2023
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6. A high-throughput mass spectrometry-based assay for large-scale profiling of circulating human apolipoproteins[S]

Author

Valentin Blanchard, Damien Garçon, Catherine Jaunet, Kevin Chemello, Stéphanie Billon-Crossouard, Audrey Aguesse, Aya Garfa, Gilles Famchon, Amada Torres, Cédric Le May, Matthieu Pichelin, Edith Bigot-Corbel, Gilles Lambert, Bertrand Cariou, Samy Hadjadj, Michel Krempf, Kalyane Bach-Ngohou, and Mikaël Croyal

Subjects
proteomics, lipoprotein metabolism, metabolic disease, assay development, isotopic labeling, lipid metabolism, Biochemistry, QD415-436
Abstract

Apolipoproteins govern lipoprotein metabolism and are promising biomarkers of metabolic and cardiovascular diseases. Unlike immunoassays, MS enables the quantification and phenotyping of multiple apolipoproteins. Hence, here, we aimed to develop a LC-MS/MS assay that can simultaneously quantitate 18 human apolipoproteins [A-I, A-II, A-IV, A-V, B48, B100, C-I, C-II, C-III, C-IV, D, E, F, H, J, L1, M, and (a)] and determined apoE, apoL1, and apo(a) phenotypes in human plasma and serum samples. The plasma and serum apolipoproteins were trypsin digested through an optimized procedure and peptides were extracted and analyzed by LC-MS/MS. The method was validated according to standard guidelines in samples spiked with known peptide amounts. The LC-MS/MS results were compared with those obtained with other techniques, and reproducibility, dilution effects, and stabilities were also assessed. Peptide markers were successfully selected for targeted apolipoprotein quantification and phenotyping. After optimization, the assay was validated for linearity, lower limits of quantification, accuracy (biases: –14.8% to 12.1%), intra-assay variability [coefficients of variation (CVs): 1.5–14.2%], and inter-assay repeatability (CVs: 4.1–14.3%). Bland-Altman plots indicated no major statistically significant differences between LC-MS/MS and other techniques. The LC-MS/MS results were reproducible over five repeated experiments (CVs: 1.8–13.7%), and we identified marked differences among the plasma and serum samples. The LC-MS/MS assay developed here is rapid, requires only small sampling volumes, and incurs reasonable costs, thus making it amenable for a wide range of studies of apolipoprotein metabolism. We also highlight how this assay can be implemented in laboratories.

Published
2020
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7. Efficacy of Antiviral Treatment in Hepatitis C Virus (HCV)-Driven Monoclonal Gammopathies Including Myeloma

Author

Alba Rodríguez-García, María Linares, María Luz Morales, Sophie Allain-Maillet, Nicolas Mennesson, Ricardo Sanchez, Rafael Alonso, Alejandra Leivas, Alfredo Pérez-Rivilla, Edith Bigot-Corbel, Sylvie Hermouet, and Joaquín Martínez-López

Subjects
infection, hepatitis (C) virus, antiviral, multiple myeloma, monoclonal gammopathies, Immunologic diseases. Allergy, RC581-607
Abstract

Multiple myeloma (MM) remains an incurable plasma cell malignancy. While its origin is enigmatic, an association with infectious pathogens including hepatitis C virus (HCV) has been suggested. Here we report nine patients with monoclonal gammopathy of undetermined significance (MGUS) or MM with previous HCV infection, six of whom received antiviral treatment. We studied the evolution of the gammopathy disease, according to anti-HCV treatment and antigen specificity of purified monoclonal immunoglobulin, determined using the INNO-LIA™ HCV Score assay, dot-blot assays, and a multiplex infectious antigen microarray. The monoclonal immunoglobulin from 6/9 patients reacted against HCV. Four of these patients received antiviral treatment and had a better evolution than untreated patients. Following antiviral treatment, one patient with MM in third relapse achieved complete remission with minimal residual disease negativity. For two patients who did not receive antiviral treatment, disease progressed. For the two patients whose monoclonal immunoglobulin did not react against HCV, antiviral treatment was not effective for MGUS or MM disease. Our results suggest a causal relationship between HCV infection and MGUS and MM progression. When HCV was eliminated, chronic antigen-stimulation disappeared, allowing control of clonal plasma cells. This opens new possibilities of treatment for MGUS and myeloma.

Published
2022
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8. Frontotemporal dementia is the leading cause of 'true' A−/T+ profiles defined with Aβ42/40 ratio

Author

Hélène Pouclet‐Courtemanche, Tri‐Bao Nguyen, Emilie Skrobala, Claire Boutoleau‐Bretonnière, Florence Pasquier, Elodie Bouaziz‐Amar, Edith Bigot‐Corbel, Susanna Schraen, Julien Dumurgier, Claire Paquet, and Thibaud Lebouvier

Subjects
Alzheimer's disease, Cerebrospinal fluid biomarkers, Aβ42/40 ratio, Aβ42/Aβ40 ratio, Frontotemporal dementia, Suspected non Alzheimer's disease pathology (SNAP), Neurology. Diseases of the nervous system, RC346-429, Geriatrics, RC952-954.6
Abstract

Abstract Introduction Patients with positive tauopathy but negative Aβ42 (A−T+) in the cerebrospinal fluid (CSF) represent a diagnostic challenge. The Aβ42/40 ratio supersedes Aβ42 and reintegrates “false” A−T+ patients into the Alzheimer's disease spectrum. However, the biomarker and clinical characteristics of “true” and “false” A−T+ patients remain elusive. Methods Among the 509 T+N+ patients extracted from the databases of three memory clinics, we analyzed T+N+ patients with normal Aβ42 and compared “false” A−T+ with abnormal Aβ42/40 ratio and “true” A−T+ patients with normal Aβ42/40 ratio, before CSF analysis and at follow‐up. Results 24.9% of T+N+ patients had normal Aβ42 levels. Among them, 42.7% were “true” A−T+. “True” A−T+ had lower CSF tauP181 than “false” A−T+ patients. 48.0% of “true” A−T+ patients were diagnosed with frontotemporal lobar degeneration before CSF analysis and 64.0% at follow‐up, as compared with 6% in the “false” A−T+ group (P < .0001). Discussion Frontotemporal lobar degeneration is probably the main cause of “true” A−T+ profiles.

Published
2019
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9. Analysis of the Targets and Glycosylation of Monoclonal IgAs From MGUS and Myeloma Patients

Author

Adrien Bosseboeuf, Célia Seillier, Nicolas Mennesson, Sophie Allain-Maillet, Maeva Fourny, Anne Tallet, Eric Piver, Philippe Lehours, Francis Mégraud, Laureline Berthelot, Jean Harb, Edith Bigot-Corbel, and Sylvie Hermouet

Subjects
monoclonal immunoglobulin A (IgA), multiple myeloma, monoclonal gammopathy of undetermined significance (MGUS), infectious antigens, Epstein–Barr virus, hepatitis C virus, Immunologic diseases. Allergy, RC581-607
Abstract

Previous studies showed that monoclonal immunoglobulins G (IgGs) of “monoclonal gammopathy of undetermined significance” (MGUS) and myeloma were hyposialylated, thus presumably pro-inflammatory, and for about half of patients, the target of the monoclonal IgG was either a virus—Epstein–Barr virus (EBV), other herpes viruses, hepatitis C virus (HCV)—or a glucolipid, lysoglucosylceramide (LGL1), suggesting antigen-driven disease in these patients. In the present study, we show that monoclonal IgAs share these characteristics. We collected 35 sera of patients with a monoclonal IgA (6 MGUS, 29 myeloma), and we were able to purify 25 of the 35 monoclonal IgAs (6 MGUS, 19 myeloma). Monoclonal IgAs from MGUS and myeloma patients were significantly less sialylated than IgAs from healthy volunteers. When purified monoclonal IgAs were tested against infectious pathogens and LGL1, five myeloma patients had a monoclonal IgA that specifically recognized viral proteins: the core protein of HCV in one case, EBV nuclear antigen 1 (EBNA-1) in four cases (21.1% of IgA myeloma). Monoclonal IgAs from three myeloma patients reacted against LGL1. In summary, monoclonal IgAs are hyposialylated and as described for IgG myeloma, significant subsets (8/19, or 42%) of patients with IgA myeloma may have viral or self (LGL1) antigen-driven disease.

Published
2020
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10. Serum Pepsinogens Combined with New Biomarkers Testing Using Chemiluminescent Enzyme Immunoassay for Non-Invasive Diagnosis of Atrophic Gastritis: A Prospective, Multicenter Study

Author

Nicolas Chapelle, Malgorzata Osmola, Jérôme Martin, Justine Blin, Maxime Leroy, Iva Jirka, Driffa Moussata, Dominique Lamarque, Raphael Olivier, David Tougeron, Anne Hay-Lombardie, Edith Bigot-Corbel, Damien Masson, Jean-François Mosnier, and Tamara Matysiak-Budnik

Subjects
atrophic gastritis, non-invasive markers, pepsinogens, diagnostic performance, Medicine (General), R5-920
Abstract

Background: Analysis of serum biomarkers for the assessment of atrophic gastritis (AG), a gastric precancerous lesion, is of growing interest for identification of patients at increased risk of gastric cancer. The aim was to analyze the diagnostic performance of serum pepsinogen testing using another method, chemiluminescent enzyme immunoassay (CLEIA), as well as of other new potential biomarkers. Material and Methods: The sera of patients considered at increased risk of gastric cancer and undergoing upper endoscopy collected in our previous prospective, multicenter study were tested for pepsinogen I (PGI) and II (PGII), interleukin-6 (IL-6), human epididymal protein 4 (HE-4), adiponectin, ferritin and Krebs von den Lungen (KL-6) using the CLEIA. The diagnostic performance for the detection of AG was calculated by taking histology as the reference. Results: In total, 356 patients (162 men (46%); mean age 58.6 (±14.2) years), including 152 with AG, were included. For the detection of moderate to severe corpus AG, sensitivity and specificity of the pepsinogen I/II ratio were of 75.0% (95%CI 57.8–87.9) and 92.6% (88.2–95.8), respectively. For the detection of moderate to severe antrum AG, sensitivity of IL-6 was of 72.2% (95%CI 46.5–90.3). Combination of pepsinogen I/II ratio or HE-4 showed a sensitivity of 85.2% (95%CI 72.9–93.4) for the detection of moderate to severe AG at any location. Conclusion: This study shows that PG testing by CLEIA represents an accurate assay for the detection of corpus AG. Additionally, IL-6 and HE-4 may be of interest for the detection of antrum AG. Mini-abstract: Pepsinogens testing by chemiluminescent enzyme immunoassay is accurate for the detection of corpus atrophic gastritis. IL-6 and HE-4 maybe of interest for the detection of antrum atrophic gastritis.

Published
2022
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11. Fatty liver index is a strong predictor of changes in glycemic status in people with prediabetes: The IT-DIAB study.

Author

Matthieu Wargny, Sarra Smati, Matthieu Pichelin, Edith Bigot-Corbel, Charlotte Authier, Violette Dierry, Yassine Zaïr, Vincent Jacquin, Samy Hadjadj, Jérôme Boursier, and Bertrand Cariou

Subjects
Medicine, Science
Abstract

Background & aimsIn patients at metabolic risk, nonalcoholic fatty liver disease is a strong and highly prevalent predictor for type 2 diabetes. Its assessment in clinical practice is not easy but the fatty liver index (FLI) could be used as a surrogate. Here, we studied the association between the FLI and the conversion to new-onset diabetes (NOD) or prediabetes reversion in patients with prediabetes.MethodsThe IT-DIAB observational study included 389 individuals with prediabetes, defined as fasting plasma glucose (FPG) between 110 and 125 mg/dL. NOD conversion was defined as a first FPG value ≥ 126 mg/dL and prediabetes reversion as a first FPG value < 110 mg/dL. The associations of both events with baseline FLI were studied separately using multivariate Cox models.ResultsAfter a median follow-up of 3.9 years (range 0.1-6.1), 138 individuals (35.5%) converted to NOD. FLI was associated with a higher risk of NOD conversion (unadjusted HR per SD = 1.54, 95%CI 1.27-1.86, pConclusionsFLI is a simple, practical score to further stratify the risk of conversion to NOD or the possibility of prediabetes reversion in clinical practice, independently of classical glucose parameters.Trial registrationClincialTrials.gov number NCT01218061 and NCT01432509.

Published
2019
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12. Comparison of Monoclonal Gammopathies Linked to Poliovirus or Coxsackievirus vs. Other Infectious Pathogens

Author

Jean Harb, Nicolas Mennesson, Cassandra Lepetit, Maeva Fourny, Margaux Louvois, Adrien Bosseboeuf, Sophie Allain-Maillet, Olivier Decaux, Caroline Moreau, Anne Tallet, Eric Piver, Philippe Moreau, Valéry Salle, Edith Bigot-Corbel, and Sylvie Hermouet

Subjects
poliovirus, coxsackievirus, monoclonal gammopathy, MGUS, multiple myeloma, monoclonal immunoglobulin, Cytology, QH573-671
Abstract

Chronic stimulation by infectious pathogens or self-antigen glucosylsphingosine (GlcSph) can lead to monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM). Novel assays such as the multiplex infectious antigen microarray (MIAA) and GlcSph assays, permit identification of targets for >60% purified monoclonal immunoglobulins (Igs). Searching for additional targets, we selected 28 purified monoclonal Igs whose antigen was not represented on the MIAA and GlcSph assays; their specificity of recognition was then analyzed using microarrays consisting of 3760 B-cell epitopes from 196 pathogens. The peptide sequences PALTAVETG and PALTAAETG of the VP1 coat proteins of human poliovirus 1/3 and coxsackievirus B1/B3, respectively, were specifically recognized by 6/28 monoclonal Igs. Re-analysis of patient cohorts showed that purified monoclonal Igs from 10/155 MGUS/SM (6.5%) and 3/147 MM (2.0%) bound to the PALTAVETG or PALTAAETG epitopes. Altogether, PALTAV/AETG-initiated MGUS are not rare and few seem to evolve toward myeloma.

Published
2021
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13. Pro-inflammatory State in Monoclonal Gammopathy of Undetermined Significance and in Multiple Myeloma Is Characterized by Low Sialylation of Pathogen-Specific and Other Monoclonal Immunoglobulins

Author

Adrien Bosseboeuf, Sophie Allain-Maillet, Nicolas Mennesson, Anne Tallet, Cédric Rossi, Laurent Garderet, Denis Caillot, Philippe Moreau, Eric Piver, François Girodon, Hélène Perreault, Sophie Brouard, Arnaud Nicot, Edith Bigot-Corbel, Sylvie Hermouet, and Jean Harb

Subjects
myeloma, monoclonal gammopathy of undetermined significance, monoclonal immunoglobulin, immunoglobulin G sialylation, infection, inflammation, Immunologic diseases. Allergy, RC581-607
Abstract

Multiple myeloma (MM) and its pre-cancerous stage monoclonal gammopathy of undetermined significance (MGUS) allow to study immune responses and the chronology of inflammation in the context of blood malignancies. Both diseases are characterized by the production of a monoclonal immunoglobulin (mc Ig) which for subsets of MGUS and MM patients targets pathogens known to cause latent infection, a major cause of inflammation. Inflammation may influence the structure of both polyclonal (pc) Ig and mc Ig produced by malignant plasma cells via the sialylation of Ig Fc fragment. Here, we characterized the sialylation of purified mc and pc IgGs from 148 MGUS and MM patients, in comparison to pc IgGs from 46 healthy volunteers. The inflammatory state of patients was assessed by the quantification in serum of 40 inflammation-linked cytokines, using Luminex technology. While pc IgGs from MGUS and MM patients showed heterogeneity in sialylation level, mc IgGs from both MGUS and MM patients exhibited a very low level of sialylation. Furthermore, mc IgGs from MM patients were less sialylated than mc IgGs from MGUS patients (p

Published
2017
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14. Long-Term Toxicity of 213Bi-Labelled BSA in Mice.

Author

Laëtitia Dorso, Edith Bigot-Corbel, Jérôme Abadie, Maya Diab, Sébastien Gouard, Frank Bruchertseifer, Alfred Morgenstern, Catherine Maurel, Michel Chérel, and François Davodeau

Subjects
Medicine, Science
Abstract

Short-term toxicological evaluations of alpha-radioimmunotherapy have been reported in preclinical assays, particularly using bismuth-213 (213Bi). Toxicity is greatly influenced not only by the pharmacokinetics and binding specificity of the vector but also by non-specific irradiation due to the circulating radiopharmaceutical in the blood. To assess this, an acute and chronic toxicity study was carried out in mice injected with 213Bi-labelled Bovine Serum Albumin (213Bi-BSA) as an example of a long-term circulating vector.Biodistribution of 213Bi-BSA and 125I-BSA were compared in order to evaluate 213Bi uptake by healthy organs. The doses to organs for injected 213Bi-BSA were calculated. Groups of nude mice were injected with 3.7, 7.4 and 11.1 MBq of 213Bi-BSA and monitored for 385 days. Plasma parameters, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN) and creatinine, were measured and blood cell counts (white blood cells, platelets and red blood cells) were performed. Mouse organs were examined histologically at different time points.Haematological toxicity was transient and non-limiting for all evaluated injected activities. At the highest injected activity (11.1 MBq), mice died from liver and kidney failure (median survival of 189 days). This liver toxicity was identified by an increase in both ALT and AST and by histological examination. Mice injected with 7.4 MBq of 213Bi-BSA (median survival of 324 days) had an increase in plasma BUN and creatinine due to impaired kidney function, confirmed by histological examination. Injection of 3.7 MBq of 213Bi-BSA was safe, with no plasma enzyme modifications or histological abnormalities.Haematological toxicity was not limiting in this study. Liver failure was observed at the highest injected activity (11.1 MBq), consistent with liver damage observed in human clinical trials. Intermediate injected activity (7.4 MBq) should be used with caution because of the risk of long-term toxicity to kidneys.

Published
2016
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15. Pathogenesis of Myeloproliferative Neoplasms: Role and Mechanisms of Chronic Inflammation

Author

Sylvie Hermouet, Edith Bigot-Corbel, and Betty Gardie

Subjects
Pathology, RB1-214
Abstract

Myeloproliferative neoplasms (MPNs) are a heterogeneous group of clonal diseases characterized by the excessive and chronic production of mature cells from one or several of the myeloid lineages. Recent advances in the biology of MPNs have greatly facilitated their molecular diagnosis since most patients present with mutation(s) in the JAK2, MPL, or CALR genes. Yet the roles played by these mutations in the pathogenesis and main complications of the different subtypes of MPNs are not fully elucidated. Importantly, chronic inflammation has long been associated with MPN disease and some of the symptoms and complications can be linked to inflammation. Moreover, the JAK inhibitor clinical trials showed that the reduction of symptoms linked to inflammation was beneficial to patients even in the absence of significant decrease in the JAK2-V617F mutant load. These observations suggested that part of the inflammation observed in patients with JAK2-mutated MPNs may not be the consequence of JAK2 mutation. The aim of this paper is to review the different aspects of inflammation in MPNs, the molecular mechanisms involved, the role of specific genetic defects, and the evidence that increased production of certain cytokines depends or not on MPN-associated mutations, and to discuss possible nongenetic causes of inflammation.

Published
2015
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17. Idiopathic normal pressure hydrocephalus and frontotemporal dementia: an unexpected association

Author

Adrien de Guilhem de Lataillade, Claire Boutoleau-Bretonnière, Jesus Aguilar-Garcia, Amandine Pallardy, Edith Bigot-Corbel, Vincent Roualdes, Julie Leroy, Philippe Damier, and Hélène Pouclet-Courtemanche

Subjects
Cellular and Molecular Neuroscience, Psychiatry and Mental health, Neurology, Biological Psychiatry
Abstract

Idiopathic normal pressure hydrocephalus has a complex multifactorial pathogenesis and is associated with Alzheimer’s disease in many patients. To date, it is not well known if a similar association exists with behavioural variant of frontotemporal lobar degeneration. In a first step, we compare the prevalence of idiopathic normal pressure hydrocephalus in two groups of patients, one with behavioural variant of frontotemporal lobar degeneration (n = 69) and the other with Alzheimer’s disease (n = 178). In the second step, we describe more precisely the phenotype of patients with the association of idiopathic normal pressure hydrocephalus and behavioural variant of frontotemporal lobar degeneration. Firstly, we report that the prevalence of idiopathic normal pressure hydrocephalus was far higher in the group of patients with behavioural variant of frontotemporal lobar degeneration than in the group of patients with Alzheimer’s disease (7.25% and 1.1%, respectively, P = 0.02). Secondly, we show that patients with the double diagnosis share common clinical and para-clinical features of both idiopathic normal pressure hydrocephalus and behavioural variant of frontotemporal lobar degeneration patients, including CSF shunting efficacy in real-life experience. Overall, our results suggest a link between these two conditions and should encourage neurologists to look for idiopathic normal pressure hydrocephalus in their behavioural variant of frontotemporal lobar degeneration patients in the event of gait disturbances; the benefit/risk balance could indeed be in favour of shunt surgery for selected patients with this newly described entity.

Published
2022
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18. Marqueurs biologiques et maladie d’Alzheimer

Author

Armand Perret-Liaudet, Isabelle Quadrio, Edith Bigot-Corbel, and Anne Hay-Lombardie

Subjects
Medical Laboratory Technology, Biochemistry (medical), Analytical Chemistry
Abstract

Resume La maladie d’Alzheimer est la plus frequente des maladies neurodegeneratives. On estime qu’environ 1 million de personnes sont atteintes de cette pathologie en France. Son evolution est progressive, des premiers stades ou l’atteinte cognitive et comportementale est legere aux stades moderes puis tardifs correspondant a une perte totale d’autonomie. Elle est caracterisee sur le plan physiopathologique par un dysfonctionnement synaptique, une perte neuronale et des agregats de proteines mal conformees : on parle alors de « proteino-pathie ». Son diagnostic est multifactoriel et repose sur un faisceau d’arguments cliniques, radiologiques, neuropsychologiques et biologiques. Ces marqueurs sont les peptides amyloides Aβ 1-40 et Aβ 1-42 et les proteines TAU totale et hyperphosphorylees, en general en position 181. Ils sont mesures dans le liquide cerebrospinal et refletent la presence des lesions cerebrales, tres precocement dans l’evolution de la maladie. La phase pre-analytique est delicate, necessitant l’utilisation d’un tube specifique. Malgre le developpement de methodes automatisees, ces dosages manquent de standardisation : les seuils sont donc dependants des techniques et des laboratoires. Il n’est pas recommande de realiser le dosage de ces marqueurs de facon systematique mais de les reserver aux formes les moins typiques ou touchant les adultes jeunes. Le dialogue clinico- biologique est alors fondamental pour la bonne interpretation des resultats.

Published
2021
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19. Marqueurs biologiques utilisés dans le diagnostic de la sclérose en plaques

Author

Anne Hay-Lombardie, Pierre-Olivier Bertho, Edith Bigot-Corbel, Maxime Carpentier, and Edouard Le Carpentier

Subjects
Medical Laboratory Technology, Biochemistry (medical), Analytical Chemistry
Abstract

Resume La sclerose en plaques (SEP) est une maladie chronique inflammatoire d’origine auto-immune, qui se caracterise par une demyelinisation progressive des neurones, conduisant a des desordres neurologiques : perturbations motrices, sensitives, cognitives, visuelles ou encore sphincteriennes. La SEP atteint plus les femmes que les hommes, est plus frequente dans les pays developpes et represente la premiere cause de handicap non traumatique du sujet jeune. Le diagnostic de la maladie repose sur un faisceau d’arguments cliniques, d’imagerie mais egalement biologiques. Plusieurs marqueurs dosables parallelement dans le serum et le liquide cerebro-spinal (LCS) ont ete etudies pour mettre en evidence l’atteinte auto-immune du systeme nerveux central (SNC). Le mieux defini est actuellement la recherche de bandes oligoclonales (BOC) d’immuno- globulines G (IgG) dans le LCS qui reflete l’activation lympho-cytaire B chronique cerebrale. La revision en 2017 des criteres diagnostiques de Mac Donald a d’ailleurs reintegre la presence de BOC comme element diagnostic. Ces dernieres annees ont vu l’emergence de nouveaux biomarqueurs quantitatifs tels que le dosage des chaines legeres libres d’Ig pour le diagnostic ou des chaines legeres de neurofilaments pour le pronostic et la reponse au traitement.

Published
2021
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20. SARS-CoV-2 and neurological disorders: the revelance of biomarkers?

Author

Katell Peoc'h, Vincent Sapin, Marie Christine Beauvieux, Sylvain Lehmann, Jean Philippe Azulay, Benoit Rucheton, Beaudeux Jl, Edith Bigot-Corbel, Cécile Delorme, Celia Raulet, and Aymeric Lanore

Subjects
medicine.medical_specialty, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), SARS-CoV-2, business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), COVID-19, Context (language use), General Medicine, Prognosis, medicine.disease, Predictive Value of Tests, Acute disseminated encephalomyelitis, Pandemic, Disease Progression, medicine, Humans, Nervous System Diseases, Intensive care medicine, business, Pandemics, Neurological impairment, Biomarkers, Biochemical markers
Abstract

Soon after the pandemic, numerous publications described cases of neurological disorders associated with the SARS-CoV-2 infection. The range of neurological symptoms is becoming increasingly more extensive as the pandemic progresses. However, it is not yet well established whether the manifestations are due to direct viral damage to the nervous system or indirect consequences of the infection. This review presents an inventory of the biochemical markers studied in the context of neurological disorders related to SARS-CoV-2. By reflecting various physiopathological mechanisms, these biomarkers allow both a better understanding of the pathophysiology of Covid-19 and a contribution to the diagnosis of neurologic troubles; they could participate in the prognostic evaluation of patients.

Published
2021
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21. Plasma haemolysis index and interleukine-6 for the early prediction of cardiac surgery-associated acute kidney injury. A proof-of-concept study

Author

Karim Lakhal, Bertrand Rozec, Fouzia Souab, Thomas Senage, Maxime Leroy, Arnaud Legrand, Elodie Boissier, and Edith Bigot-Corbel

Subjects
Advanced and Specialized Nursing, Radiology, Nuclear Medicine and imaging, General Medicine, Cardiology and Cardiovascular Medicine, Safety Research
Abstract

Introduction Haemolysis and inflammation contribute to cardiac surgery-associated acute kidney injury (CS-AKI). We aimed to assess the performance of plasma haemolysis index (HI) and interleukine-6 (IL-6) for the prediction of all-stage CS-AKI. We also assessed their ability to predict moderate-to-severe CS-AKI and to discriminate persistent from transient CS-AKI. Methods Adult patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) were prospectively included. Haemolysis index and IL-6 were measured immediately after the end of CPB and 6 hours later. Correction for haemodilution relied upon changes in albuminaemia. Persistent CS-AKI was defined as a steady/increasing CS-AKI stage between the 48th and the 60th postoperative hour as compared with the worst stage observed within the 48 first hours. Results Among 82 patients, CS-AKI occurred in 37 (45%) patients. Postoperative HI and IL-6 were positively correlated to the duration of CPB (r ≤ 0.51, p ≤ 0.0003). Whether we considered isolated measurements of HI or IL-6, their indexation to haemodilution or not, their kinetics and/or their combination, the prediction of all stage CS-AKI was inaccurate (area under the receiver operating characteristic curve [AUCROC]≤ 0.68) whereas moderate-to-severe CS-AKI (6 patients only) was predicted with an honourable performance (AUCROC = 0.77 [95%CI 0.67;0.86] and 0.87 [95%CI 0.77;0.93] for HI and IL-6, respectively). The persistent/transient nature of CS-AKI was inaccurately predicted (AUCROC ≤ 0.68). Conclusions In a population in which most CS-AKI cases were mild, although they frequently (41%) persisted >48 hours, CS-AKI was inaccurately predicted by HI and/or IL-6. A better performance for moderate-to-severe CS-AKI prediction is likely. These preliminary findings are yet to be validated.

Published
2022

22. Kappa Free Light Chain Biomarkers Are Efficient for the Diagnosis of Multiple Sclerosis: A Large Multicenter Cohort Study

Author

Michael Levraut, Sabine Laurent-Chabalier, Xavier Ayrignac, Kévin Bigaut, Manon Rival, Sanae Squalli, Hélène Zéphir, Tifanie Alberto, Jean-David Pekar, Jonathan Ciron, Damien Biotti, Bénédicte Puissant-Lubrano, Jean-Philippe Camdessanché, Yannick Tholance, Olivier Casez, Bertrand Toussaint, Jeanne Marion, Thibault Moreau, Daniela Lakomy, Audrey Thomasset, Elisabeth Maillart, Delphine Sterlin, Aude Maurousset, Auriane Rocher, David Axel Laplaud, Edith Bigot-Corbel, Pierre-Olivier Bertho, Jean Pelletier, Joseph Boucraut, Pierre Labauge, Thierry Vincent, Jérôme De Sèze, Isabelle Jahn, Barbara Seitz-Polski, Eric Thouvenot, Christine Lebrun-Frenay, Université Côte d'Azur - Faculté de Médecine (UCA Faculté Médecine), Université Côte d'Azur (UCA), Unité de Recherche Clinique de la Côte d’Azur (URRIS UR2CA), Centre Hospitalier Universitaire de Nice (CHU Nice)-Université Côte d'Azur (UCA), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Département de neurologie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), Les Hôpitaux Universitaires de Strasbourg (HUS), Thèses d'exercice et mémoires - UFR de Médecine Montpellier-Nîmes, Université de Montpellier (UM), Laboratoire de Biochimie [CHRU Nîmes], Département de neurologie [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Pôle Neurosciences [CHU Toulouse], Institut Fédératif de Biologie (IFB), Service de Neurologie [CHU de Saint-Étienne], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Jean Monnet - Saint-Étienne (UJM), Institut NeuroMyoGène (INMG), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Centre Hospitalier Universitaire [Grenoble] (CHU), Translational microbial Evolution and Engineering (TIMC-TrEE), Translational Innovation in Medicine and Complexity / Recherche Translationnelle et Innovation en Médecine et Complexité - UMR 5525 (TIMC ), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA), Pathologie cellulaire : aspects moléculaires et viraux / Pathologie et Virologie Moléculaire, Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), Centre d'épidémiologie des populations (CEP), Université de Bourgogne (UB)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Service de Biochimie [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre de Recherche en Transplantation et Immunologie - Center for Research in Transplantation and Translational Immunology (U1064 Inserm - CR2TI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Team 5 : Neuroinflammation, mechanisms, therapeutic options (NEMO) (U1064 Inserm - CR2TI), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Laboratoire de Biochimie [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Département de Biochimie [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes)-Hôpital Nord Laennec [CHU Nantes], Hôpital de la Timone [CHU - APHM] (TIMONE), Aix Marseille Université (AMU), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Institut de Neurosciences des Systèmes (INS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CIC Strasbourg (Centre d’Investigation Clinique Plurithématique (CIC - P) ), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Nouvel Hôpital Civil de Strasbourg-Hôpital de Hautepierre [Strasbourg], CHU Strasbourg, Laboratoire Immunologie [Nice], Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Hôpital de l'Archet-Université Côte d'Azur (UCA), Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Service de Neurologie [CHU Nice], Hôpital Pasteur [Nice] (CHU)-Centre Hospitalier Universitaire de Nice (CHU Nice), Société Francophone de la Sclérose En Plaques (SFSEP)., and Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)

Subjects
MESH: Humans, MESH: Multiple Sclerosis, Multiple Sclerosis, MESH: Demyelinating Diseases* / diagnosis, [SDV]Life Sciences [q-bio], Oligoclonal Bands, MESH: Immunoglobulin kappa-Chains, MESH: Central Nervous System Diseases, MESH: Oligoclonal Bands, Cohort Studies, Immunoglobulin kappa-Chains, Neurology, Central Nervous System Diseases, MESH: Biomarkers, Humans, Female, Neurology (clinical), MESH: Cohort Studies, MESH: Female, Biomarkers, Demyelinating Diseases
Abstract

Background and ObjectivesKappa free light chains (KFLC) seem to efficiently diagnose MS. However, extensive cohort studies are lacking to establish consensus cut-offs, notably to rule out non-MS autoimmune CNS disorders. Our objectives were to (1) determine diagnostic performances of CSF KFLC, KFLC index, and KFLC intrathecal fraction (IF) threshold values that allow us to separate MS from different CNS disorder control populations and compare them with oligoclonal bands' (OCB) performances and (2) to identify independent factors associated with KFLC quantification in MS.MethodsWe conducted a retrospective multicenter study involving 13 French MS centers. Patients were included if they had a noninfectious and nontumoral CNS disorder, eligible data concerning CSF and serum KFLC, albumin, and OCB. Patients were classified into 4 groups according to their diagnosis: MS, clinically isolated syndrome (CIS), other inflammatory CNS disorders (OIND), and noninflammatory CNS disorder controls (NINDC).ResultsOne thousand six hundred twenty-one patients were analyzed (675 MS, 90 CIS, 297 OIND, and 559 NINDC). KFLC index and KFLC IF had similar performances in diagnosing MS from nonselected controls and OIND (p= 0.123 andp= 0.991 for area under the curve [AUC] comparisons) and performed better than CSF KFLC (p< 0.001 for all AUC comparisons). A KFLC index of 8.92 best separated MS/CIS from the entire nonselected control population, with better performances than OCB (p< 0.001 for AUC comparison). A KFLC index of 11.56 best separated MS from OIND, with similar performances than OCB (p= 0.065). In the multivariate analysis model, female gender (p= 0.003), young age (p= 0.013), and evidence of disease activity (p< 0.001) were independent factors associated with high KFLC index values in patients with MS, whereas MS phenotype, immune-modifying treatment use at sampling, and the FLC analyzer type did not influence KFLC index.DiscussionKFLC biomarkers are efficient tools to separate patients with MS from controls, even when compared with other patients with CNS autoimmune disorder. Given these results, we suggest using KFLC index or KFLC IF as a criterion to diagnose MS.Classification of EvidenceThis study provides Class III evidence that KFLC index or IF can be used to differentiate patients with MS from nonselected controls and from patients with other autoimmune CNS disorders.

Published
2022
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23. A high-throughput mass spectrometry-based assay for large-scale profiling of circulating human apolipoproteins[S]

Author

Mikaël Croyal, Amada Torres, Catherine Jaunet, Gilles Lambert, Kévin Chemello, Michel Krempf, Kalyane Bach-Ngohou, Cédric Le May, Matthieu Pichelin, Audrey Aguesse, Edith Bigot-Corbel, Stéphanie Billon-Crossouard, Samy Hadjadj, Gilles Famchon, Aya Garfa, Valentin Blanchard, Bertrand Cariou, Damien Garçon, unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), ANR-16-RHUS-0007,ANR-16-RHUS-0007,CHOPIN(2016), Diabète athérothrombose et thérapies Réunion Océan Indien (DéTROI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de La Réunion (UR), Centre hospitalier universitaire de Nantes (CHU Nantes), Physiopathologie des Adaptations Nutritionnelles (PhAN), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Mass Spectrometry Core Facility [Nantes] (CRNH-O ), Centre de Recherche en Nutrition Humaine Ouest [UNIV Nantes] (CRNHO), Université de Nantes (UN), The Enteric Nervous System in gut and brain disorders [U1235] (TENS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), and ANR-16-RHUS-0007,CHOPIN,CHOPIN(2016)

Subjects
0301 basic medicine, Apolipoprotein E, assay development, Apolipoprotein B, Peptide, serum lipid, QD415-436, 030204 cardiovascular system & hematology, Mass spectrometry, Proteomics, Biochemistry, Mass Spectrometry, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, proteomics, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Limit of Detection, lipid metabolism, medicine, Methods, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Humans, isotopic labeling, ComputingMilieux_MISCELLANEOUS, chemistry.chemical_classification, lipoprotein metabolism, Reproducibility, Chromatography, biology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Cell Biology, Repeatability, plasma lipid, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Trypsin, metabolic disease, 030104 developmental biology, Apolipoproteins, chemistry, biology.protein, Blood Chemical Analysis, medicine.drug, Chromatography, Liquid
Abstract

International audience; Apolipoproteins govern lipoprotein metabolism and are promising biomarkers of metabolic and cardiovascular diseases. Unlike immunoassays, MS enables the quantification and phenotyping of multiple apolipoproteins. Hence, here, we aimed to develop a LC-MS/MS assay that can simultaneously quantitate 18 human apolipoproteins [A-I, A-II, A-IV, A-V, B48, B100, C-I, C-II, C-III, C-IV, D, E, F, H, J, L1, M, and (a)] and determined apoE, apoL1, and apo(a) phenotypes in human plasma and serum samples. The plasma and serum apolipoproteins were trypsin digested through an optimized procedure and peptides were extracted and analyzed by LC-MS/MS. The method was validated according to standard guidelines in samples spiked with known peptide amounts. The LC-MS/MS results were compared with those obtained with other techniques, and reproducibility, dilution effects, and stabilities were also assessed. Peptide markers were successfully selected for targeted apolipoprotein quantification and phenotyping. After optimization, the assay was validated for linearity, lower limits of quantification, accuracy (biases: -14.8% to 12.1%), intra-assay variability [coefficients of variation (CVs): 1.5-14.2%], and inter-assay repeatability (CVs: 4.1-14.3%). Bland-Altman plots indicated no major statistically significant differences between LC-MS/MS and other techniques. The LC-MS/MS results were reproducible over five repeated experiments (CVs: 1.8-13.7%), and we identified marked differences among the plasma and serum samples. The LC-MS/MS assay developed here is rapid, requires only small sampling volumes, and incurs reasonable costs, thus making it amenable for a wide range of studies of apolipoprotein metabolism. We also highlight how this assay can be implemented in laboratories.

Published
2020
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24. Urinary strips for protein assays: easy to do but difficult to interpret!

Author

Etienne Cavalier, Pierre Delanaye, Edith Bigot-Corbel, Laurence Piéroni, and Guillaume Résimont

Subjects
Urinary protein, medicine.medical_specialty, Urinary albumin, Urinary system, Population, 030232 urology & nephrology, Urine, Urinalysis, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Pregnancy, medicine, Albuminuria, Humans, Mass Screening, Intensive care medicine, education, Reagent Strips, education.field_of_study, Proteinuria, business.industry, medicine.disease, Clinical Practice, Nephrology, Female, medicine.symptom, business, Kidney disease
Abstract

Urine samples can be readily obtained from patients in everyday clinical practice. Therefore, the availability of urine allows physicians to obtain relevant clinical information in a timely manner. Since the measurement of urinary protein levels is essential in diagnosing and treating a host of diseases, the potential detection of urinary proteins by urinary strips in an easy, quick, and cheap way is very attractive. However, to ensure optimal use of urinary strips, one needs to be aware of their characteristics and their limitations. In this review, we discuss the characteristics of the urinary strips available for testing urinary protein levels and for detecting urinary albumin. We then consider their analytical performances in their most widely used clinical applications (e.g., in pregnancy, chronic kidney disease, diabetes, and screening of the general population).

Published
2020
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25. Effect of Parathyroidectomy on Metabolic Homeostasis in Primary Hyperparathyroidism

Author

Samuel Frey, Raphaël Bourgade, Cédric Le May, Mikaël Croyal, Edith Bigot-Corbel, Nelly Renaud-Moreau, Matthieu Wargny, Cécile Caillard, Eric Mirallié, Bertrand Cariou, Claire Blanchard, Centre hospitalier universitaire de Nantes (CHU Nantes), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Structure fédérative de recherche François Bonamy (SFR François Bonamy), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche en Santé de l'Université de Nantes (IRS-UN), Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Institut des maladies de l'appareil digestif [Nantes] (IMAD), and Le May, Cedric

Subjects
cardiovascular risk factors, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, diabetes, endocrine system diseases, [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], primary hyperparathyroidism, parathyroidectomy, dyslipidemia, insulin resistance, PCSK9, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, General Medicine, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO]
Abstract

International audience; Background: The benefits of parathyroidectomy on cardiovascular risk in primary hyperparathyroidism (PHPT) are controversial. This monocentric, observational, prospective study aimed to assess the effects of parathyroidectomy on glucose and lipid metabolism in classic or mild PHPT.Methods: Patients who underwent parathyroidectomy for classic (calcemia >2.85 mmol/L) or mild PHPT (calcemia ≤2.85 mmol/L) between 2016 and 2019 were included. A metabolic assessment was performed before and 1 year after parathyroidectomy. Patients with a history of diabetes were excluded.Results: Nineteen patients had classic and 120 had mild PHPT. Ninety-five percent were normocalcemic 6 months after surgery. Fasting plasma glucose and insulin levels decreased after parathyroidectomy in patients with mild PHPT (p < 0.001). HOMA-IR decreased after surgery in the overall population (p < 0.001), while plasma adiponectin concentrations increased in patients with both classic (p = 0.005) and mild PHPT (p < 0.001). Plasma triglyceride levels decreased significantly only in patients with classic PHPT (p = 0.021). Plasma PCSK9 levels decreased in patients with mild PHPT (p < 0.001).Conclusions: Parathyroidectomy for PHPT improves insulin resistance and decreases plasma triglyceride levels in classic PHPT and plasma PCSK9 levels in mild PHPT. Further studies are needed to better characterize the consequences of such metabolic risk factors' improvements on cardiovascular events.

Published
2022
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26. History of bariatric surgery and COVID-19 outcomes in patients with type 2 diabetes: Results from the CORONADO study

Author

Natacha Germain, Matthieu Wargny, François Pattou, Claire Blanchard, Sophie Borot, Lyse Bordier, Dominique Seret-Bégué, Edith Bigot-Corbel, Bruno Vergès, Bertrand Cariou, Christine Coffin-Boutreux, Céline Gonfroy-Leymarie, Olivier Bourron, Laurent Meyer, Ronan Roussel, Pierre Gourdy, Gaëtan Prévost, Béatrice Guyomarch, Anne Dutour, Charles Thivolet, Matthieu Pichelin, Tanguy Perennec, Blandine Tramunt, Sarra Smati, Samy Hadjadj, Cyrielle Caussy, CarMeN, laboratoire, Institut des maladies de l'appareil digestif [Nantes] (IMAD), Centre hospitalier universitaire de Nantes (CHU Nantes), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Institut des Maladies Métaboliques et Casdiovasculaires (UPS/Inserm U1297 - I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Hôpital d'Instruction des Armées Begin, Service de Santé des Armées, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hospices Civils de Lyon (HCL), CENTRE HOSPITALIER PÉRIGUEUX (CHP), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Saint-Etienne, Université Jean Monnet - Saint-Étienne (UJM), Centre Hospitalier René Dubos [Pontoise], Les Hôptaux universitaires de Strasbourg (HUS), CHU Strasbourg, Département d'Endocrinologie, Diabète et Maladies Métaboliques [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Centre Hospitalier de Gonesse (CHU Gonesse), Service d'Endocrinologie, Diabétologie et Maladies Métaboliques (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Recherche translationnelle sur le diabète - U 1190 (RTD), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), FCRIN/FORCE Network, Centre d'investigation clinique (CIC) de Nantes -CIC Plurithématique (CIC 0004 - Nantes), Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), École Pratique des Hautes Études (EPHE), and Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)

Subjects
Diabetes duration, medicine.medical_specialty, animal structures, Coronavirus disease 2019 (COVID-19), Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Medicine (miscellaneous), Bariatric Surgery, Type 2 diabetes, Endocrinology, COVID‐19, Diabetes mellitus, medicine, Humans, In patient, Viral, Brief Cutting Edge Report, Retrospective Studies, Mechanical ventilation, Diabetes Mellitus, Nutrition and Dietetics, business.industry, SARS-CoV-2, COVID-19, medicine.disease, Surgery, Type 2 Diabetes, [SDV] Life Sciences [q-bio], Metabolic and Bariatric Surgery, Diabetes Mellitus, Type 2, covid-19, RNA, Viral, RNA, Observational study, business, Body mass index, Type 2
Abstract

International audience; OBJECTIVE: This study assessed the impact of a history of metabolic and bariatric surgery (MBS) on the clinical outcomes in patients with type 2 diabetes (T2D) and severe obesity hospitalized for COVID-19. METHODS: In this post hoc analysis from the nationwide observational CORONADO (Coronavirus SARS-CoV2 and Diabetes Outcomes) study, patients with T2D and a history of MBS were matched with patients without MBS for age, sex, and BMI either at the time of MBS or on admission for COVID-19. The composite primary outcome (CPO) combined invasive mechanical ventilation and/or death within 7 and 28 days following admission. RESULTS: Out of 2,398 CORONADO participants, 20 had a history of MBS. When matching for BMI at the time of MBS and after adjustment for diabetes duration, the CPO occurred less frequently within 7 days (3 vs. 17 events, OR: 0.15 [0.01 to 0.94], p = 0.03) and 28 days (3 vs. 19 events, OR: 0.11 [0.01 to 0.71], p = 0.02) in patients with MBS (n = 16) vs. controls (n = 44). There was no difference in CPO rate between patients with MBS and controls when matching for BMI on admission. CONCLUSIONS: These data are reassuring regarding COVID-19 prognosis in patients with diabetes and a history of MBS compared with those without MBS.

Published
2022
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27. Plasma apolipoprotein concentrations and incident diabetes in subjects with prediabetes

Author

Mikaël Croyal, Matthieu Wargny, Kevin Chemello, Chloé Chevalier, Valentin Blanchard, Edith Bigot-Corbel, Gilles Lambert, Cédric Le May, Samy Hadjadj, Bertrand Cariou, Centre hospitalier universitaire de Nantes (CHU Nantes), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Centre de microscopie électronique [UNIV Nantes] (SFR Santé - Hôtel Dieu), Université de Nantes (UN)-Hôtel-Dieu de Nantes-Centre hospitalier universitaire de Nantes (CHU Nantes), Santé - François Bonamy, Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche en Santé de l'Université de Nantes (IRS-UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Mass Spectrometry Core Facility [Nantes] (CRNH-O ), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Service de Santé publique - Clinique des données [CHU Nantes] (Pôle Hospitalo-Universitaire 11), Diabète athérothrombose et thérapies Réunion Océan Indien (DéTROI), Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of British Columbia (UBC), Laboratoire de Biochimie [CHU Nantes], Hôpital Guillaume-et-René-Laennec [Saint-Herblain], and Le May, Cedric

Subjects
Male, Time Factors, endocrine system diseases, [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Endocrinology, Diabetes and Metabolism, Risk Assessment, Mass Spectrometry, Prediabetic State, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Predictive Value of Tests, Risk Factors, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Diseases of the circulatory (Cardiovascular) system, Humans, Prospective Studies, Aged, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Incidence, nutritional and metabolic diseases, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Type 2 diabetes, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Middle Aged, Apolipoprotein L1, Prognosis, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, IT-Diab study, New-onset diabetes, Apolipoproteins, Clusterin, Diabetes Mellitus, Type 2, RC666-701, Disease Progression, Female, Apolipoprotein E, France, Cardiology and Cardiovascular Medicine, Biomarkers
Abstract

Background The identification of circulating biomarkers associated with the risk of type 2 diabetes (T2D) is useful for improving the current prevention strategies in the most at-risk patients. Here, we aimed to investigate the association of plasma apolipoprotein concentrations in prediabetes subjects with the incidence of new-onset T2D during follow-up. Methods In the IT-DIAB prospective study, 307 participants with impaired fasting glucose levels (fasting plasma glucose [FPG]: 110–125 mg/dL) were followed yearly for 5 years. The onset of T2D was defined as a first FPG value ≥ 126 mg/dL during follow-up. Apolipoprotein (apo)A-I, A-II, A-IV, B100, C-I, C-II, C-III, C-IV, D, E, F, H, J, L1, M, and (a) plasma concentrations were determined by mass spectrometry. Correlations between apolipoproteins and metabolic parameters at baseline were assessed by Spearman’s coefficients. Kaplan–Meier curves were drawn using a ternary approach based on terciles and incident T2D. The association between plasma apolipoproteins concentrations and the incidence of T2D was determined using Cox proportional-hazards models. Results During a median follow-up of 5-year, 115 participants (37.5%) developed T2D. After adjustment for age, sex, body mass index, FPG, HbA1c, and statin use, the plasma levels of apoC-I, apoC-II, apoC-III, apoE, apoF, apoH, apoJ, and apoL1 were positively associated with a high risk for T2D. After further adjustment for plasma triglycerides, only apoE (1 SD natural-log-transformed hazard ratio: 1.28 [95% confidence interval: 1.06; 1.54]; p = 0.010), apoF (1.22 [1.01; 1.48]; p = 0.037), apoJ (1.24 [1.03; 1.49]; p = 0.024), and apoL1 (1.26 [1.05; 1.52]; p = 0.014) remained significantly associated with the onset of T2D. Kaplan–Meier survival curves also showed that the lower third of plasma apoE levels (p = 0.002) compared to the middle and upper thirds. Conclusions The plasma apoE levels are positively associated with the risk of T2D in prediabetes subjects, independently of traditional risk factors. The possible associations of apoF, apoJ, and apoL1 with T2D risk also pave the way for further investigations. Trial registration This trial was registered at clinicaltrials.gov as NCT01218061 and NCT01432509

Published
2021
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28. Efficacy of Antiviral Treatment in Hepatitis C Virus (HCV)-Driven Monoclonal Gammopathies Including Myeloma

Author

Alba Rodríguez-García, María Linares, María Luz Morales, Sophie Allain-Maillet, Nicolas Mennesson, Ricardo Sanchez, Rafael Alonso, Alejandra Leivas, Alfredo Pérez-Rivilla, Edith Bigot-Corbel, Sylvie Hermouet, Joaquín Martínez-López, Instituto de Investigación Sanitaria Hospital 12 de Octubre [Madrid, Spain] (I2SH), Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers (CRCI2NA ), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Immunology and New Concepts in ImmunoTherapy (INCIT), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Hospital Universitario 12 de Octubre [Madrid], Laboratoire de Biochimie [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Département d'Hématologie [CHU Nantes], and Dupuis, Christine

Subjects
Male, [SDV.IMM] Life Sciences [q-bio]/Immunology, [SDV]Life Sciences [q-bio], Immunology, Paraproteinemias, Hepacivirus, Antibodies, Viral, Antiviral Agents, Monoclonal Gammopathy of Undetermined Significance, hepatitis (C) virus, Immunology and Allergy, Humans, Aged, Original Research, monoclonal gammopathies, Antibodies, Monoclonal, RC581-607, Middle Aged, Viral Load, Hepatitis C, antiviral, infection, [SDV] Life Sciences [q-bio], multiple myeloma, Treatment Outcome, Disease Progression, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Disease Susceptibility, Immunologic diseases. Allergy, Biomarkers
Abstract

International audience; Multiple myeloma (MM) remains an incurable plasma cell malignancy. While its origin is enigmatic, an association with infectious pathogens including hepatitis C virus (HCV) has been suggested. Here we report nine patients with monoclonal gammopathy of undetermined significance (MGUS) or MM with previous HCV infection, six of whom received antiviral treatment. We studied the evolution of the gammopathy disease, according to anti-HCV treatment and antigen specificity of purified monoclonal immunoglobulin, determined using the INNO LIA™ HCV Score assay, dot-blot assays, and a multiplex infectious antigen microarray. The monoclonal immunoglobulin from 6/9 patients reacted against HCV. Four of these patients received antiviral treatment and had a better evolution than untreated patients. Following antiviral treatment, one patient with MM in third relapse achieved complete remission with minimal residual disease negativity. For two patients who did not receive antiviral treatment, disease progressed. For the two patients whose monoclonal immunoglobulin did not react against HCV, antiviral treatment was not effective for MGUS or MM disease. Our results suggest a causal relationship between HCV infection and MGUS and MM progression. When HCV was eliminated, chronic antigen-stimulation disappeared, allowing control of clonal plasma cells. This opens new possibilities of treatment for MGUS and myeloma.

Published
2021
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29. Early recognition of cardiac surgery-associated acute kidney injury: lack of added value of TIMP2 IGFBP7 over short-term changes in creatinine (an observational pilot study)

Author

Edith Bigot-Corbel, Arnaud Legrand, Lucile Figueres, Floris Chabrun, Thomas Senage, Karim Lakhal, Émilie Sacchetto, Bertrand Rozec, Maxime Leroy, Hôpital Guillaume-et-René-Laennec [Saint-Herblain], MethodS in Patients-centered outcomes and HEalth ResEarch (SPHERE), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), Hôtel-Dieu de Nantes, Centre hospitalier universitaire de Nantes (CHU Nantes), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), and Malbec, Odile

Subjects
Male, Tissue inhibitor of Metalloproteinase-2/urine* [MeSH], [SDV]Life Sciences [q-bio], Pilot Projects, law.invention, chemistry.chemical_compound, 0302 clinical medicine, Aortic valve replacement, 030202 anesthesiology, law, Anesthesiology, RD78.3-87.3, Prospective Studies, Aged, 80 and over, Heart Valve Prosthesis Implantation, Cardiopulmonary Bypass, biology, Acute kidney injury, Insulin-like growth factor binding proteins/urine* [MeSH], Acute Kidney Injury, Cardiac surgery, [SDV] Life Sciences [q-bio], Insulin-Like Growth Factor Binding Proteins, Creatinine/blood [MeSH], Lipocalins/metabolism* [MeSH], 030220 oncology & carcinogenesis, Aortic Valve, Cardiac surgical procedures [MeSH], Female, medicine.medical_specialty, Urology, Context (language use), Sensitivity and Specificity, 03 medical and health sciences, medicine, Cardiopulmonary bypass, Humans, Acute kidney injury [MeSH], Cystatin C, Aged, Creatinine, Tissue Inhibitor of Metalloproteinase-2, business.industry, Research, Perioperative, medicine.disease, Anesthesiology and Pain Medicine, Early Diagnosis, chemistry, biology.protein, business, Tissue inhibitor of Metalloproteinase-2 [MeSH], Biomarkers
Abstract

Background For the detection of cardiac surgery-associated acute kidney injury (CS-AKI), the performance of urine tissue inhibitor of metalloproteinase 2 insulin-like growth factor-binding protein 7 (TIMP2 IGFBP7) has never been compared with that of very early changes in plasma creatinine (∆pCr). We hypothesized that, in the context of perioperative haemodilution, lack of postoperative decrease in pCr would be of honourable performance for the detection of CS-AKI. We therefore aimed at comparing these biomarkers and their kinetics (primary objective). As secondary objectives, we assessed plasma neutrophil gelatinase-associated lipocalin (pNGAL), cystatin C (pCysC) and urea (pUrea). We also determined the ability of these biomarkers to early discriminate persistent from transient CS-AKI. Methods Patients over 75 years-old undergoing aortic valve replacement with cardiopulmonary bypass (CPB) were included in this prospective observational study. Biomarkers were measured before/after CPB and at the sixth postoperative hour (H6). Results In 65 patients, CS-AKI occurred in 27 (42%). ∆pCr from post-CPB to H6 (∆pCrpostCPB-H6): outperformed TIMP2 IGFBP7 at H6 and its intra- or postoperative changes: area under the receiver operating characteristic curve (AUCROC) of 0.84 [95%CI:0.73–0.92] vs. ≤0.67 [95%CI:0.54–0.78], p ≤ 0.03. The AUCROC of pNGAL, pCysC and pUrea did not exceed 0.72 [95%CI:0.59–0.83]. Indexing biomarkers levels for blood or urine dilution did not improve their performance. Combining TIMP2 IGFBP7 and ∆pCrpostCPB-H6 was of no evident added value over considering ∆pCrpostCPB-H6 alone. For the early recognition of persistent CS-AKI, no biomarker outperformed ∆pCrpostCPB-H6 (AUCROC = 0.69 [95%CI:0.48–0.85]). Conclusions In this hypothesis-generating study mostly testing early detection of mild CS-AKI, there was no evident added value of the tested modern biomarkers over early minimal postoperative changes in pCr: despite the common perioperative hemodilution in the setting of cardiac surgery, if pCr failed to decline within the 6 h after CPB, the development of CS-AKI was likely. Confirmatory studies with more severe forms of CS-AKI are required.

Published
2021
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30. Author response for 'Influenza vaccination and prognosis of COVID ‐19 in hospitalized patients with diabetes: Results from the CORONADO study'

Author

null A Diallo, null M Pichelin, null M Wargny, null P Gourdy, null JB Bonnet, null S Hadjadj, null B Cariou, null A Sultan, null F Galtier, null Matthieu Wargny, null Pascale Mahot, null Bertrand Cariou, null Samy Hadjadj, null Matthieu Pichelin, null Anne‐Laure Fournier‐Guilloux, null Nicolas Mauduit, null Edith Bigot‐Corbel, null Anne‐Sophie Boureau, null Laure Dekcer, null Audrey Ernould, null Claire Primot, null Anne Seguin, null Marielle Joliveau, null Sonia Pouvreau, null Chloé FOURNIER, null Jeremy Thureau, null Edith Fonteneau, null Pamela Hublain, null Chu Nantes, null Carole Agasse, null Mathilde DE Kergaradec, null Vincent Minville, null Fanny Vardon‐Bounes, null Guillaume Martin‐Blondel, null Pierre Gourdy, null Blandine Tramunt, null Marie‐Christine Turnin, null Hélène Hanaire, null Jean‐Michel Mansuy, null Didier Fabre, null Marie‐Blanche Arhainx, null Laurent Cazals, null Laure Combes, null Emmanuelle Lami, null Mallory Cianferani, null Bruno Megarbane, null Pierre Leroy, null Jean‐François Gautier, null Tiphaine Vidal‐Trecan, null Jean‐Pierre Riveline, null Jean‐Louis Laplanche, null Stéphane Mouly, null Louis Potier, null Ronan Roussel, null Malak Taher, null Yawa Abouleka, null Fetta Yaker, null Aurelie Carlier, null Anne Boutten, null Marilyne Hallot‐Feron, null Fadila Mourah, null Charles Thivolet, null Emilie Blond, null Muriel Rolland, null Josep Verdecho Mendez, null Marine Alexandre, null Julien Pottecher, null Emilie Richer, null Laurent Meyer, null Florina Luca, null Jean‐Marc Lessinger, null Thibault Bahougne, null Bruno Guerci, null Lisa Ludwig, null Siham Benzirar, null Catherine Malaplate, null Thierry Matton, null Julien Poissy, null Karine Faure, null Pierre Fontaine, null Florence Baudoux, null Anne Vambergue, null Jean David Pekar, null Marc Lambert, null Cécile Yelnik, null Amélie Bruandet, null Laurent Petit, null Didier Neau, null Vincent Rigalleau, null Annie Berard, null Amandine Galioot, null Remy Coudroy, null Arnaud Thille, null René Robert, null France Roblot‐Cazenave, null Blandine Rammaert, null Pierre Jean Saulnier, null Xavier Piguel, null Nesrine Benhenda, null Camille Husson, null Celine Olivier, null Florence Torremocha, null Mathilde Fraty, null Marie Flamen d'assigny, null Aurelie Miot, null Valentin Bossard, null Kada Klouche, null Alain Makinson, null Ariane Sultan, null Jean‐Baptiste Bonnet, null Vincent Foulongne, null Florence Galtier, null Cécile Aubron, null Séverine Ansart, null Véronique Kerlan, null Pascale Quiniou, null Jean‐Luc Carre, null Stéphane Quesnot, null Bruno Laviolle, null Carole Schwebel, null Olivier Epaulard, null Pierre‐Yves Benhamou, null Cécile Betry, null Anne‐Laure Borel, null Sandrine Lablanche, null Dorra Guergour, null Catherine Duclos, null Emmanuel Cosson, null Erwan Guyot, null Aurore Deniau, null Phucthutrang Nguyen, null Yves Reznik, null Michael Joubert, null Stéphane Allouche, null Lydia Guittet, null Steven Grange, null Manuel Etienne, null Gaëtan Prévost, null Valéry Brunel, null Jean‐Christophe Lagier, null Didier Raoult, null Anne Dutour, null Bénédicte Gaborit, null Sandrine Boulllu, null Patrice Darmon, null Adèle Lasbleiz, null Mathieu Cerino, null Fanny Romain, null Marie Houssays, null Jean Pierre Quenot, null Lionel Piroth, null Bruno Vergès, null Laurence Duvillard, null Bernard Bonnotte, null Alain Mercat, null Vincent Dubee, null Ingrid Allix, null Patrice Rodien, null Robin Dhersin, null Maylis Lebeault, null Wojciech Trzepizur, null Jocelyne Loison, null Antoine Brangier, null Pierre Asfar, null Pascal Reynier, null Françoise Larcher, null Françoise Joubaud, null Marie‐Rita Andreu, null Geoffrey Urbanski, null Laurent Hubert, null Cedric Annweiler, null Jean Dellamonica, null Johan Courjon, null Nicolas Chevalier, null Giulia Chinetti, null Magda Chafai, null Bruno Mourvillier, null Firouze Bani‐Sadr, null Sarra Barraud, null Brigitte Delemer, null Philippe Gillery, null Pascale Labedade, null Amélie Chabrol, null Alfred Penfornis, null Catherine Petit, null Coralie Amadou, null Maxime Adler, null Clément Dubost, null Pierre‐Louis Conan, null Lyse Bordier, null Franck Ceppa, null Cyril Garcia, null Mathilde Sollier, null Olivier Dupuy, null Sophie Laplance, null Olivier Billuart, null Marie Joseph Aroulanda, null Frédérique Olivier, null Florence Ayon, null Nathalie Wilhelm, null Loic Epelboin, null Nadia Sabbah, null Aurelie Charpin, null Pierre Squara, null Olivier Belliard, null Claude Dubois, null Michel Marre, null Johann Auchabie, null Roxane Courtois, null Thierry Duriez, null Tiphaine Mergey, null Laura Vallee, null Laetitia Seguin, null Abdallah Al‐Salameh, null Jean‐Philippe Lanoix, null Sandrine Soriot‐Thomas, null Anne‐Marie Bourgeois‐Descouls, null Rachel Desailloud, null Natacha Germain, null Bogdan Galusca, null Gwenaelle Belleton, null Nesrine Marouani, null Delia Palaghiu, null Amira Hammour, null Fernando Berdaguer, null Thimothée Klopfenstein, null Hajer Zayet, null Patrice Winiszewski, null Marie Zanusso, null Pauline Garnier, null Ingrid Julier, null Karim Hamzaoui, null Sophie Marty‐Gres, null Tarik Sadki, null Lucile Cadot, null Jean‐Louis Dubost, null Céline Gonfroy, null Catherine Campinos, null Pascale Martres, null Marie Pierre Coulhon, null Nicolas Allou, null Marwa Bachir, null Stella Hoang, null Candice Kembellec, null Olivia Suply, null Fatima Kharcha, null Anne‐Claire Devouge, null Anna Flaus‐Furmanuk, null Isabelle Madeline, null Vincent Ehinger, null Sophie Bastard, null Loic Raffray, null Frederic Renou, null Aude Bojarski, null Caroline Paul, null Karine Borsu, null Angelique Gorlin, null Servane Bernardo, null Carole Truong Ut, null Stephane Renaud, null Antoine Vignoles, null Emilie Foch, null Laurie Masse, null Hubert Grand, null Helene Ferrand, null Christelle Raffaitin‐Cardin, null Hadjer Zellagui, null Celine Castang‐Brachet, null Frederique Boury, null Ana Alvarez Tena, null Isabelle Moura, null Pierre Kalfon, null Juliana Darasteanu, null Arnaud Monier, null Pascal Foucault, null Alexandra Depuille, null Stéphanie Laugier‐Robiolle, null Patrick Caneiro, null Maud Basso, null Etienne Larger, null Samir Bouam, null Wahiba Benzenati, null Leila Ait Bachir, null Camille Cussac Pillegand, null Marc Vasse, null Christophe Michard, null Nathanaëlle Montanier, null Luc Millot, null Françoise Crepet, null Danielle Ratsimba, null Kevin Bouiller, null Sophie Borot, null Isabelle Bruckert, null Annie Clergeot, null Franck Schillo, null Dorothée Vignes, null Muriel Bourgeon‐Ghittori, null Hamoud Lachgar, null Claire Lambert DE Cursay, null Stéphane Levante, null Jean Charles Auregan, null Antoine Merlet, null Cécile Zaragoza, null Gwénaëlle Arnault, null Anne‐Gaëlle Loupp, null Olivier Lesieur, null Mariam Roncato‐Saberan, null Didier Gouet, null Romain Lemarie, null Hong_an Allano, null Emmanuel Vivier, null Caroline Pariset, null Cédric Luyton, null Lucien Marchand, null Fanny Doroszewski, null Matthieu Pecquet, null Laurent Perard, null Sylvie Vuillermoz‐Blas, null Nicolas Kacki, null Patricia Charrier, null Amélie Ducet‐Boiffard, null Françoise Desroys Roure, null Olivier Bourron, null Dominique Bonnefont‐Rousselot, null Suzanne Laroche, null Franck Phan, null Agnès Hartemann, null Cyrielle Caussy, null Emmanuel Disse, null Claude Guerin, null Thomas Perpoint, null Philippe Moulin, null Régine Cartier, null Geoffroy Hariri, null Dorothée Chopin, null Camille Vatier, null Nathalie Bourcigaux, null Emmanuelle Chaigneau, null Sophie Christin‐Maitre, null Bruno Donadille, null Bruno Feve, null Sophie Lamothe, null Julie Sarfati, null Pascal Pernet, null Anne Chambon, null Delphine Demarsy, null Hugo Campagne, null Françoise Latil‐Plat, null Monica Berne, null Marilyne Grinand, null Marion Touzet, null Aydrey Zabulon, null Jocelyne Craspag, null Catherine Ledoux, null Cedric Contaret, null Blandine Janand‐Delenne, null Anaïs Giraud, null Marie Lou Lacrimini, null Joëlle Arrivie, null Deborah Ancelle, null Carine Guillois, null Bénédicte Fremy, null Amina Chaalal, null Gaëlle Barrande, null Anne Dorange, null Eglantine Rouanet, null Dominique Seret‐Begue, null Audrey Saoud, null Anne‐Marie Guedj, null Nathalie Bedos, null Fritz‐Line Velayoudom, null Marie Dumas, null Benoite Gonda, null Christine Coffin, null Stéphanie Gibiat, null Myriam Lungo, null Chantal Bully, null Pierre Serusclat, null Stella Bully, null Patricia Carre, null Jean‐Philippe Leberre, null Carlos Elkhoury, null Marine Thieux, null Laetitia Paradisi‐Prieur, and null CORONADO investigators

Subjects
Vaccination, Pediatrics, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), business.industry, Hospitalized patients, Diabetes mellitus, Medicine, business, medicine.disease
Published
2021
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31. Haemolysis index: validation for haemolysis detection during extracorporeal membrane oxygenation

Author

Philippe Bizouarn, Bertrand Rozec, Johanna Nicolet, Edith Bigot-Corbel, Thierry Lepoivre, Mickael Vourc'h, Thomas Senage, Karim Lakhal, Elodie Boissier, and Jean-Christian Roussel

Subjects
medicine.medical_specialty, business.industry, medicine.medical_treatment, Acute kidney injury, Reproducibility of Results, Acute Kidney Injury, medicine.disease, Haemolysis, Hemolysis, law.invention, Extracorporeal Membrane Oxygenation, Anesthesiology and Pain Medicine, law, Free haemoglobin, Internal medicine, Extracorporeal membrane oxygenation, Cardiopulmonary bypass, Cardiology, Humans, Medicine, Prospective Studies, business
Published
2020
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32. Insights on glycated albumin

Author

Saïd Kamel, Edith Bigot-Corbel, and Anne Hay-Lombardie

Subjects
Blood Glucose, Glycated Hemoglobin, Glycation End Products, Advanced, High concentration, medicine.medical_specialty, Chemistry, Albumin, General Medicine, Prognosis, medicine.disease, Glycated albumin, Endocrinology, Diabetes Mellitus, Type 2, Predictive Value of Tests, Renal Dialysis, Glycation, Internal medicine, medicine, Humans, Diabetic Nephropathies, Glycated Serum Albumin, Plasma Albumin, Serum Albumin, Monitoring, Physiologic, Kidney disease
Abstract

Like all proteins, plasma albumin can undergo glycation to produce glycated albumin. This glycation will change the structure and therefore functionalities of albumin. Because of its accessibility, its high concentration and its half-life the glycation of albumin is greater than that of haemoglobin. Laboratory measurement of glycated albumin is possible. The value of glycated albumin reflects the glycaemic balance over a period of 3 weeks, and shows its interest in cases where the determination of HbA1c is impossible or deficient. It also seems that the glycated albumin has a prognostic interest in the chronic kidney disease patients dialyzed or not. In some patients, the assay of glycated albumin could replace measurement of fructosamines and provide additional information to HbA1c values.

Published
2019
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33. Interférences liées à la biotine sur les paramètres d’urgence

Author

Vincent Debarre, Edith Bigot-Corbel, and Anne Hay-Lombardie

Subjects
03 medical and health sciences, Medical Laboratory Technology, 0302 clinical medicine, 030220 oncology & carcinogenesis, Biochemistry (medical), 030204 cardiovascular system & hematology, Analytical Chemistry
Abstract

Resume Depuis la publication par l’Agence nationale de securite du medicament en juillet 2017 d’une reactovigilance sur l’interference de la biotine sur certains immuno-dosages, les biologistes medicaux sont sensibilises a cette potentielle interference. De nombreux parametres doses par des methodes et des reactifs differents sont concernes. Le risque de rendre un resultat errone sur un parametre d’urgence doit etre pris en compte. En presence de hautes ou tres hautes doses de biotine il y a potentiellement un risque de sous-estimation des parametres mesures par methode « sandwich » et un risque de surestimation des resultats des parametres mesures par competition. Il convient a chaque laboratoire de lister les parametres potentiellement impactes et de mettre en place des mesures limitant les erreurs potentielles.

Published
2019
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34. Comparison of Monoclonal Gammopathies Linked to Poliovirus or Coxsackievirus vs. Other Infectious Pathogens

Author

Adrien Bosseboeuf, Philippe Moreau, Caroline Moreau, Olivier Decaux, Valéry Salle, Anne Tallet, Margaux Louvois, Cassandra Lepetit, Sylvie Hermouet, Maeva Fourny, Nicolas Mennesson, Edith Bigot-Corbel, Jean Harb, Sophie Allain-Maillet, Eric Piver, Molecular Mechanisms of Chronic Inflammation in Hematological Diseases (CRCINA-ÉQUIPE 16), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Université de Nantes (UN)-Université de Nantes (UN), Laboratoire de Biochimie [Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Service de Médecine interne et immunologie clinique [Rennes] = internal medicine and clinical immunology [Rennes], CHU Pontchaillou [Rennes], Laboratoire de Biochimie [Rennes], Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Laboratoire de Biochimie [CHRU Tours], Morphogénèse et antigénicité du VIH et du virus des Hépatites (MAVIVH - U1259 Inserm - CHRU Tours ), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Tours, Service d'Hématologie [Nantes], CHU Amiens-Picardie, Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Bernardo, Elizabeth

Subjects
0301 basic medicine, Adult, Microarray, Paraproteinemias, Coxsackievirus Infections, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Coxsackievirus, medicine.disease_cause, Epitope, Article, 03 medical and health sciences, 0302 clinical medicine, Antigen, [SDV.CAN] Life Sciences [q-bio]/Cancer, hemic and lymphatic diseases, medicine, Humans, Multiplex, lcsh:QH301-705.5, Aged, Retrospective Studies, Aged, 80 and over, coxsackievirus, poliovirus, monoclonal immunoglobulin, Poliovirus, monoclonal gammopathy, General Medicine, MGUS, multiple myeloma, infection, pathogen, antigen specificity, Middle Aged, medicine.disease, biology.organism_classification, Virology, 3. Good health, 030104 developmental biology, lcsh:Biology (General), 030220 oncology & carcinogenesis, Monoclonal, Monoclonal gammopathy of undetermined significance
Abstract

International audience; Chronic stimulation by infectious pathogens or self-antigen glucosylsphingosine (GlcSph) can lead to monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM). Novel assays such as the multiplex infectious antigen microarray (MIAA) and GlcSph assays, permit identification of targets for >60% purified monoclonal immunoglobulins (Igs). Searching for additional targets, we selected 28 purified monoclonal Igs whose antigen was not represented on the MIAA and GlcSph assays; their specificity of recognition was then analyzed using microarrays consisting of 3760 B-cell epitopes from 196 pathogens. The peptide sequences PALTAVETG and PALTAAETG of the VP1 coat proteins of human poliovirus 1/3 and coxsackievirus B1/B3, respectively, were specifically recognized by 6/28 monoclonal Igs. Re-analysis of patient cohorts showed that purified monoclonal Igs from 10/155 MGUS/SM (6.5%) and 3/147 MM (2.0%) bound to the PALTAVETG or PALTAAETG epitopes. Altogether, PALTAV/AETG-initiated MGUS are not rare and few seem to evolve toward myeloma.

Published
2021
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35. Phenotypic Differences Between Polygenic and Monogenic Hypobetalipoproteinemia

Author

Sybil Charrière, Bertrand Cariou, Matthieu Pichelin, Alain Carrié, Noël Peretti, Richard Redon, Pierre Antoine Rollat-Farnier, Mathilde Di Filippo, René Valéro, Marie Marrec, Matthieu Wargny, Eléonore Divry, O. Marmontel, Edith Bigot-Corbel, X. Vanhoye, Pierre Lindenbaum, Philippe Moulin, Emmanuelle Génin, Antoine Rimbert, Dramane Coulibaly, Jean-François Deleuze, Gilles Degraef, Didier Goxe, Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Hospices Civils de Lyon (HCL), Hôpital Louis Pradel [CHU - HCL], Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de Génomique d'Evry (IG), Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Génétique, génomique fonctionnelle et biotechnologies (UMR 1078) (GGB), EFS-Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Caisse primaire d'assurance maladie (CPAM), Centre hospitalier universitaire de Nantes (CHU Nantes), ANR-16-RHUS-0007,CHOPIN,CHOPIN(2016), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de Biochimie Endocrinienne et Oncologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Institut Brestois Santé Agro Matière (IBSAM), and Université de Brest (UBO)-Université de Brest (UBO)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Adult, Male, Multifactorial Inheritance, hypobetalipoproteinemias, liver diseases, [SDV]Life Sciences [q-bio], Down-Regulation, 030204 cardiovascular system & hematology, Biology, Risk Assessment, Fifth percentile, Young Adult, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Non-alcoholic Fatty Liver Disease, Risk Factors, medicine, Humans, Genetic Predisposition to Disease, Retrospective Studies, 030304 developmental biology, Lipoprotein cholesterol, Genetics, 0303 health sciences, Cholesterol, cholesterol, Cholesterol, LDL, medicine.disease, Phenotype, 3. Good health, chemistry, Apolipoprotein B-100, Mutation (genetic algorithm), polygenic risk score, Female, Polygenic risk score, Hypobetalipoproteinemia, Proprotein Convertase 9, mutation, Cardiology and Cardiovascular Medicine, apolipoproteins, Biomarkers
Abstract

Objective: Primary hypobetalipoproteinemia is characterized by LDL-C (low-density lipoprotein cholesterol) concentrations below the fifth percentile. Primary hypobetalipoproteinemia mostly results from heterozygous mutations in the APOB and PCSK9 genes, and a polygenic origin is hypothesized in the remaining cases. Hypobetalipoproteinemia patients present an increased risk of nonalcoholic fatty liver disease and steatohepatitis. Here, we compared hepatic alterations between monogenic, polygenic, and primary hypobetalipoproteinemia of unknown cause. Approach and Results: Targeted next-generation sequencing was performed in a cohort of 111 patients with hypobetalipoproteinemia to assess monogenic and polygenic origins using an LDL-C-dedicated polygenic risk score. Forty patients (36%) had monogenic hypobetalipoproteinemia, 38 (34%) had polygenic hypobetalipoproteinemia, and 33 subjects (30%) had hypobetalipoproteinemia from an unknown cause. Patients with monogenic hypobetalipoproteinemia had lower LDL-C and apolipoprotein B plasma levels compared with those with polygenic hypobetalipoproteinemia. Liver function was assessed by hepatic ultrasonography and liver enzymes levels. Fifty-nine percent of patients with primary hypobetalipoproteinemia presented with liver steatosis, whereas 21% had increased alanine aminotransferase suggestive of liver injury. Monogenic hypobetalipoproteinemia was also associated with an increased prevalence of liver steatosis (81% versus 29%, P Conclusions: This study highlights the importance of genetic diagnosis in the clinical care of primary hypobetalipoproteinemia patients. It shows for the first time that a polygenic origin of hypobetalipoproteinemia is associated with a lower risk of liver steatosis and liver injury versus monogenic hypobetalipoproteinemia. Thus, polygenic risk score is a useful tool to establish a more personalized follow-up of primary hypobetalipoproteinemia patients.

Published
2021
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36. An O-GlcNAcylomic Approach Reveals ACLY as a Potential Target in Sepsis in the Young Rat

Author

Didier Vertommen, Justine Dontaine, Charlotte Betus, Anaïs Maillard, Matthieu Rivière, Angélique Erraud, Thomas Pelé, Laurent Bultot, Jacques Lebreton, Benjamin Lauzier, Aurélia A. Leroux, Jérôme Montnach, A. Persello, M. Denis, Bertrand Rozec, Michel De Waard, Edith Bigot-Corbel, J. Dhot, Luc Bertrand, T. Dupas, Arnaud Tessier, Tessier, Arnaud, Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Université Catholique de Louvain = Catholic University of Louvain (UCL), Sanofi Aventis R&D [Chilly-Mazarin], Centre hospitalier universitaire de Nantes (CHU Nantes), Chimie Et Interdisciplinarité : Synthèse, Analyse, Modélisation (CEISAM), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Walloon Excellence in Life sciences and BIOtechnology [Liège] (WELBIO), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)

Subjects
Lipopolysaccharides, Lipopolysaccharide, ATP citrate lyase, [SDV]Life Sciences [q-bio], Stimulation, chemistry.chemical_compound, 0302 clinical medicine, O-GlcNAcylation, Biology (General), Spectroscopy, mass spectrometry, 0303 health sciences, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Acetylation, General Medicine, Shock, Septic, 3. Good health, Computer Science Applications, [SDV] Life Sciences [q-bio], Chemistry, Shock (circulatory), medicine.symptom, medicine.medical_specialty, Mean arterial pressure, QH301-705.5, Catalysis, Article, Acetylglucosamine, Inorganic Chemistry, Sepsis, 03 medical and health sciences, O-GlcNAcylomics, children, Internal medicine, medicine, Animals, Physical and Theoretical Chemistry, QD1-999, Molecular Biology, 030304 developmental biology, Septic shock, business.industry, Organic Chemistry, medicine.disease, [CHIM.ORGA] Chemical Sciences/Organic chemistry, Rats, Endocrinology, Blood pressure, chemistry, ATP Citrate (pro-S)-Lyase, Fluid Therapy, septic shock, business, Protein Processing, Post-Translational, 030217 neurology & neurosurgery
Abstract

Sepsis in the young population, which is particularly at risk, is rarely studied. O-GlcNAcylation is a post-translational modification involved in cell survival, stress response and metabolic regulation. O-GlcNAc stimulation is beneficial in adult septic rats. This modification is physiologically higher in the young rat, potentially limiting the therapeutic potential of O-GlcNAc stimulation in young septic rats. The aim is to evaluate whether O-GlcNAc stimulation can improve sepsis outcome in young rats. Endotoxemic challenge was induced in 28-day-old rats by lipopolysaccharide injection (E. Coli O111:B4, 20 mg·kg−1) and compared to control rats (NaCl 0.9%). One hour after lipopolysaccharide injection, rats were randomly assigned to no therapy, fluidotherapy (NaCl 0.9%, 10 mL·kg−1) ± NButGT (10 mg·kg−1) to increase O-GlcNAcylation levels. Physiological parameters and plasmatic markers were evaluated 2h later. Finally, untargeted mass spectrometry was performed to map cardiac O-GlcNAcylated proteins. Lipopolysaccharide injection induced shock with a decrease in mean arterial pressure and alteration of biological parameters (p &lt, 0.05). NButGT, contrary to fluidotherapy, was associated with an improvement of arterial pressure (p &lt, 0.05). ATP citrate lyase was identified among the O-GlcNAcylated proteins. In conclusion, O-GlcNAc stimulation improves outcomes in young septic rats. Interestingly, identified O-GlcNAcylated proteins are mainly involved in cellular metabolism.

Published
2021
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38. International initiative for harmonization of cerebrospinal fluid diagnostic comments in Alzheimer's disease

Author

Mari L DeMarco, Clementine Gondolf, Léonor Nogueira, Michael Khalil, Koen Poesen, Aurélie Bedel, Andreas Jeromin, Marie-Céline Blanc, Daniel Alcolea, Markus Otto, Agnieszka Kulczyńska-Przybik, Marc Suárez-Calvet, Benoit Rucheton, Muriel Quillard-Muraine, Hermann Esselmann, Maria Bjerke, Alberto Lleó, Anne Fogli, Frédérique Grandhomme, Olivier Bousiges, Federico Verde, M D'Onofrio, Oriol Grau-Rivera, Ashvini Keshavan, Hayrettin Tumani, Melanie Hart, Isabelle Quadrio, Sylvain Lehmann, Albert Puig‐Pijoan, Lucie Vaudran, Marcel M. Verbeek, Lucilla Parnetti, Peter Koertvelyessy, Catherine Malaplate, Armand Perret-Liaudet, Henrik Zetterberg, Jens Wiltfang, Lisa Vermunt, Chinedu T. Udeh-Momoh, Katell Poec, Claire Paquet, Magda Tsolaki, Barbara Mroszko, Jean-Baptiste Oudart, Jean-Louis Laplanche, Sebastiaan Engelborghs, Miles D. Chapman, Elodie Bouaziz Amar, Jonathan Vogelgsang, Susanna Schraen, Edith Bigot-Corbel, Elisabetta Galloni, Adelina Orellana, Constance Delaby, Anne Beaume, Diane Dufour-Rainfray, and Charlotte E. Teunissen

Subjects
medicine.medical_specialty, Epidemiology, business.industry, Health Policy, Harmonization, Disease, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Cerebrospinal fluid, Developmental Neuroscience, medicine, Neurology (clinical), Geriatrics and Gerontology, Intensive care medicine, business
Published
2020
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39. Anti-Glucosylsphingosine Autoimmunity, JAK2V617F-Dependent Interleukin-1β and JAK2V617F-Independent Cytokines in Myeloproliferative Neoplasms

Author

Edith Bigot-Corbel, Cédric Cleyrat, Eun Ho Eunice Choi, Laura Dufeu, Jean-Marc Gombert, François Girodon, Sophie Allain-Maillet, Nicolas Mennesson, Adrien Bosseboeuf, Yannick Le Bris, Olivier Mansier, Eric Lippert, Magali Pettazzoni, Sylvie Hermouet, Mégane Bostoën, Molecular Mechanisms of Chronic Inflammation in Hematological Diseases (CRCINA-ÉQUIPE 16), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), The University of New Mexico [Albuquerque], Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Hématologie [CHU Bordeaux], CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Génétique, génomique fonctionnelle et biotechnologies (UMR 1078) (GGB), Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Regulation of Bcl2 and p53 Networks in Multiple Myeloma and Mantle Cell Lymphoma (CRCINA-ÉQUIPE 10), Service d'Hématologie [Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Laboratoire d'immunologie [CHU Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service d'Hématologie Clinique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Biochimie et Biologie Moléculaire Grand Est [HCL, Lyon] (Centre de Biologie et de Pathologie), Hospices Civils de Lyon (HCL), Laboratoire de Biochimie [Nantes], Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), EFS-Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, and Bernardo, Elizabeth

Subjects
0301 basic medicine, Cancer Research, IL-1Rα, medicine.medical_treatment, Clone (cell biology), interleukin-1β (IL-1β), Inflammation, [SDV.CAN]Life Sciences [q-bio]/Cancer, myeloproliferative neoplasms (MPNs), CALR exon 9 mutants, IP-10, medicine.disease_cause, lcsh:RC254-282, leptin, Article, Autoimmunity, Proinflammatory cytokine, Pathogenesis, 03 medical and health sciences, 0302 clinical medicine, Polycythemia vera, JAK2V617F, [SDV.CAN] Life Sciences [q-bio]/Cancer, glucolipids, hemic and lymphatic diseases, medicine, article clinique, auto-immunity, antigenic stimulation, business.industry, CRISPR technology, UT-7, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, glucosylsphingosine (GlcSph), cytokines, 3. Good health, Interleukin 33, 030104 developmental biology, Cytokine, Oncology, inflammation, 030220 oncology & carcinogenesis, Immunology, IL-33, medicine.symptom, business
Abstract

Inflammatory cytokines play a major role in myeloproliferative neoplasms (MPNs) as regulators of the MPN clone and as mediators of clinical symptoms and complications. Firstly, we investigated the effect of JAK2V617F on 42 molecules linked to inflammation. For JAK2V617F-mutated patients, the JAK2V617F allele burden (%JAK2V617F) correlated with the levels of IL-1&beta, IL-1R&alpha, IP-10 and leptin in polycythemia vera (PV), and with IL-33 in ET, for all other molecules, no correlation was found. Cytokine production was also studied in the human megakaryocytic cell line UT-7. Wild-type UT-7 cells secreted 27/42 cytokines measured. UT-7 clones expressing 50% or 75% JAK2V617F were generated, in which the production of IL-1&beta, IP-10 and RANTES was increased, other cytokines were not affected. Secondly, we searched for causes of chronic inflammation in MPNs other than driver mutations. Since antigen-driven selection is increasingly implicated in the pathogenesis of blood malignancies, we investigated whether proinflammatory glucosylsphingosine (GlcSph) may play a role in MPNs. We report that 20% (15/75) of MPN patients presented with anti-GlcSph IgGs, distinguished by elevated levels of 11 cytokines. In summary, only IL-1&beta, and IP-10 were linked to JAK2V617F both in patients and in UT-7 cells, other inflammation-linked cytokines in excess in MPNs were not. For subsets of MPN patients, a possible cause of inflammation may be auto-immunity against glucolipids.

Published
2020
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40. Bile acids associate with glucose metabolism, but do not predict conversion from impaired fasting glucose to diabetes

Author

Matthieu Pichelin, Marielle Joliveau, Edith Bigot-Corbel, Amandine Descat, Bart Staels, Oscar Chávez-Talavera, Rémy Hanf, Cédric Le May, Jean-François Goossens, Emmanuelle Vallez, Samy Hadjadj, Mostafa Kouach, Matthieu Wargny, Bertrand Cariou, Anne Tailleux, unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Derudas, Marie-Hélène, EGID Diabetes Pole - - EGID2010 - ANR-10-LABX-0046 - LABX - VALID, Infrastructure Française de Protéomique - - ProFI2010 - ANR-10-INBS-0008 - INBS - VALID, Bile acid, immune-metabolism, lipid and glucose homeostasis - ImmunoBile - - H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) 2016-09-01 - 2021-08-31 - 694717 - VALID, Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 (RNMCD), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Unité de recherche de l'institut du thorax (ITX-lab), Université de Lille, Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365 (GRITA), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Molecular Mechanisms of Chronic Inflammation in Hematological Diseases (CRCINA-ÉQUIPE 16), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Genfit SA [Loos, France], Entreprise biopharmaceutique GENFIT Loos, ANR-10-LABX-0046,EGID,EGID Diabetes Pole(2010), ANR-10-INBS-0008,ProFI,Infrastructure Française de Protéomique(2010), European Project: 694717,H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) ,ImmunoBile(2016), Le May, Cedric, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), and Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)

Subjects
Male, liquid chromatography tandem mass spectrometry, [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Endocrinology, Diabetes and Metabolism, ECLIA, Takeda G protein coupled Receptor 5, UDCA, electrochemiluminescent enzyme immunoassay, hazard ratio, 0302 clinical medicine, Endocrinology, SFSTP, Chenodeoxycholic acid, CYP, HR, 6α-OH, Glucose homeostasis, fasting plasma glucose, HCA, Relationship between Insulin Sensitivity and Cardiovascular disease cohort, T2D, Prospective Studies, cholesterol associated with low density lipoproteins, 6α-hydroxylated, DCA, triglycerides, ComputingMilieux_MISCELLANEOUS, NOD, LCA, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, cholic acid, [SDV] Life Sciences [q-bio], FPG, cholesterol associated with high density lipoproteins, FXR, deoxycholic acid, Disease Progression, CYP27A1, ANR, 7α-hydroxy-4-cholesten-3-one, standard deviation, non-diabetic group, CYP cholesterol 27α-hydroxylase, medicine.medical_specialty, high molecular weight, interquartile range, IFG, Carbohydrate metabolism, HDCA, 03 medical and health sciences, Agence Nationale pour la Recherche, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Glucose Intolerance, tandem mass spectrometry, MS/MS, Humans, LC-MS/MS, 12α-hydroxylated, Aged, C4, methanol, SD, CYP cholesterol 7α-hydroxylase, medicine.disease, MeOH, HMW, hyocholic acid, Bile acids, 030104 developmental biology, Glucose, chemistry, Diabetes Mellitus, Type 2, glucagon-like peptide-1, homeostasis model assessment of insulin resistance, IR, CDCA, LDL-c, GLP-1, Prediabetes, Biomarkers, farnesoid X receptor, 0301 basic medicine, CYP7A1, [SDV]Life Sciences [q-bio], Société Française des Sciences et Techniques Pharmaceutiques, Type 2 diabetes, HOMA-IR, Bile acids Impaired fasting glucose Prediabetes New onset diabetes Hyocholic acid C4 HOMA-IR 12α-OH, BAs, Cohort Studies, chemistry.chemical_compound, impaired fasting glucose, insulin resistance, new onset diabetes, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, CA, IQR, TGR5, total cholesterol, RISC, Middle Aged, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, ursodeoxycholic acid, lithocholic acid, Female, chenodeoxycholic acid, HDL-c, TG, type 2 diabetes, TC, Adult, cytochrome P450, 030209 endocrinology & metabolism, body mass index, Bile Acids and Salts, Prediabetic State, BMI, Insulin resistance, Predictive Value of Tests, Internal medicine, Diabetes mellitus, medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], HbA 1C, business.industry, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Impaired fasting glucose, hyodeoxycholic acid, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, ND, business, Follow-Up Studies, glycated hemoglobin
Abstract

International audience; Objective: Bile acids (BAs) are signaling molecules controlling lipid and glucose metabolism. Since BA alterations are associated with obesity and insulin resistance, plasma BAs have been considered candidates to predict type 2 diabetes (T2D) risk. We aimed to determine (1) the association of BAs with glucose homeostasis parameters and (2) their predictive association with the risk of conversion from prediabetes to new-onset diabetes (NOD) in a prospective cohort study. Design: 205 patients with impaired fasting glucose (IFG) were followed each year during 5 years in the IT-DIAB cohort study. Twenty-one BA species and 7α-hydroxy-4-cholesten-3-one (C4), a marker of BA synthesis, were quantified by LC/MS-MS in plasma from fasted patients at baseline. Correlations between plasma BA species and metabolic parameters at baseline were assessed by Spearman's coefficients and the association between BAs and NOD was determined using Cox proportional-hazards models. Results: Among the analyzed BA species, total hyocholic acid (HCA) and the total HCA/total chenodeoxycholic acid (CDCA) ratio, reflecting hepatic BA 6α-hydroxylation activity, negatively correlated with BMI and HOMA-IR. The total HCA/total CDCA ratio also correlated negatively with HbA 1C. Conversion from IFG to NOD occurred in 33.7% of the participants during the follow-up. Plasma BA species were not independently associated with the conversion to NOD after adjustment with classical T2D risk factors. Conclusions: Fasting plasma BAs are not useful clinical biomarkers for predicting NOD in patients with IFG. However, an unexpected association between 6α-hydroxylated BAs and glucose parameters was found, suggesting a role for this specific BA pathway in metabolic homeostasis. IT-DIAB study registry number: NCT01218061.

Published
2020
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41. Hepatitis C Virus (HCV)-Driven Monoclonal Gammopathies and Myeloma

Author

Sylvie Hermouet, Alba Rodríguez-García, Alfredo Pérez-Rivilla, Nicolas Mennesson, Ricardo Sánchez, María Linares Gómez, María Luz Morales, Edith Bigot-Corbel, Joaquin Martinez-Lopez, Rafael Feito Alonso, Alejandra Leivas, and Sophie Allain-Maillet

Subjects
Oncology, medicine.medical_specialty, Hematology, business.industry, Hepatitis C virus, Cancer, Plasma cell, medicine.disease_cause, medicine.disease, medicine.anatomical_structure, Internal medicine, Monoclonal, medicine, business, Viral load, Multiple myeloma, Monoclonal gammopathy of undetermined significance
Abstract

Background: Multiple myeloma remains an incurable plasma cell malignancy. While its origin is enigmatic, an association with infectious pathogens including hepatitis C virus (HCV) has been suggested. Methods: We studied thirteen patients with monoclonal gammopathy of undetermined significance (MGUS) or multiple myeloma with previous HCV infection. Viral load was quantified using the VERIS MDx system. The antigen specificity of purified monoclonal immunoglobulins was determined using the INNO-LIA HCV Score, dot-blot assays, and a multiplex infectious-antigen microarray. Findings: The target of the purified monoclonal immunoglobulin was identified for 8/13 patients. The monoclonal immunoglobulin from 6/8 patients reacted against HCV. Four of the patients received antiviral treatment and had a better evolution than untreated patients. Following antiviral treatment, one patient with multiple myeloma in third relapse achieved complete remission with minimal residual disease negativity, as assessed by next generation multiparameter flow cytometry. Two patients did not receive antiviral treatment and progressed. For the two additional patients whose monoclonal immunoglobulin did not react against HCV, antiviral treatment was not effective for MGUS or multiple myeloma disease. Interpretation: Our results suggest a causal relationship between HCV infection and MGUS and multiple myeloma progression. When HCV is eliminated, chronic antigen-stimulation disappears, allowing control of clonal plasma cells. This opens new possibilities of treatment for MGUS and multiple myeloma. Funding Statement: This work was supported by grants to S.H. from the Ligue Nationale contre le Cancer (Comites Departementaux 44, 56, 29, 85, 35) and International Myeloma Foundation (IMF) (Brian D. Novis senior grant). We acknowledge of Instituto de Investigacion Hospital 12 de Octubre (i+12), CIBERONC, AECC (Accelerator Award), and the CRIS foundation for their help. M.L. had a postdoctoral fellowship from the Spanish Ministry of Economy and Competitiveness (FPDI-2013-16409) and a grant from the Spanish Society of Hematology Declaration of Interests: All authors declare no conflicts of interest. Ethics Approval Statement: The study was approved by our Institutional Review Board and the patients provided written informed consent in accordance with the Declaration of Helsinki.

Published
2020
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42. Biomarqueurs permettant le suivi de l’équilibre glycémique du patient diabétique

Author

Edith Bigot-Corbel and Anne Hay-Lombardie

Subjects
03 medical and health sciences, Medical Laboratory Technology, 0302 clinical medicine, Biochemistry (medical), 030209 endocrinology & metabolism, 030204 cardiovascular system & hematology, Analytical Chemistry
Abstract

RESUME Les marqueurs biologiques permettant la surveillance de l’equilibre glycemique des patients diabetiques sont des proteines ayant subi le phenomene de glycation. En effet, la glycation des proteines est d’autant plus importante que la glycemie est mal controlee. L’HbA1c, parametre le plus utilise, permet un apercu de l’equilibre glycemique sur les 2 a 3 mois precedant le dosage. Les recommandations de la HAS pour la prise en charge du patient diabetique sont basees sur la valeur de l’HbA1C, du fait de son interet clairement demontre, de sa standardisation et de l’automatisation du dosage. Dans les cas ou l’evaluation de l’equilibre glycemique sur une periode plus courte est requise et/ou chez les patients diabetiques presentant des perturbations de l’hemoglobine ou de la duree de vie des globules rouges, le recours a d’autres marqueurs est possible. Les fructosamines qui representent l’ensemble des proteines plasmatiques qlyquees et l’albumine glyquee vont permettre d’evaluer l’equilibre glycemique sur une periode d’environ 3 semaines. La glycation des proteines plasmatiques est plus rapide et plus importante que celle de l’hemoglobine, rendant difficile les correlations entre ces trois marqueurs. De nombreuses etudes montrent qu’en plus de son interet dans la surveillance de l’equilibre glycemique, l’albumine glyquee, du fait des modifications de structure induite par la glycation, est particulierement interessante chez le diabetique insuffisant renal chronique, dialyse ou non.

Published
2018
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43. O-GlcNAc levels stimulation improves survival at the early phase of septic shock in the young

Author

Benjamin Lauzier, M. Denis, Angélique Erraud, Arnaud Tessier, C. Gauthier, M. De Waard, T. Dupas, Bertrand Rozec, A. Persello, Jacques Lebreton, and Edith Bigot-Corbel

Subjects
medicine.medical_specialty, Mean arterial pressure, education.field_of_study, business.industry, Septic shock, medicine.medical_treatment, Population, Stimulation, medicine.disease, Sepsis, Basal (phylogenetics), Endocrinology, Internal medicine, Shock (circulatory), medicine, medicine.symptom, Cardiology and Cardiovascular Medicine, business, education, Saline
Abstract

Background We have shown that increase in O-GlcNAc levels, a post-translational modification, at the early phase of septic shock in adult (84 days old rats) resulted in a 3-fold increase in survival time. Most studies focus only in adults, and the population most affected by septic shock, young children, is rarely studied. Sepsis, with a mortality rate of 29%, is an important but preventable cause of pediatric death worldwide. Considering that basal O-GlcNAc levels are higher in the young, the potential impact of O-GlcNAc stimulation at the early phase of septic shock in the young should be evaluated. Purpose Evaluate if O-GlcNAc stimulation could improve sepsis outcomes in young. Methods Endotoxemic shock was induced in 28 days old rats with an i.v. injection of saline (CTRL) or LPS (O111:B4, 20 mg.kg−1 – LPS). 1 hour after LPS rats were randomly assigned to no therapy (LPS), fluidotherapy (saline, 10 mL.kg−1 – LPS + R) ± NButGT (10 mg.kg−1 – NButGT) to increase O-GlcNAc levels. 2 hours later, physiological functions and plasmatic markers were measured and used in adapted Pediatric RISk of Mortality score (PRISM score). The impact of treatment on survival was evaluated on n = 64. Results LPS induced a shock (mean arterial pressure (MAP): CTRL: 67.2 ± 1.9; LPS: 50.7 ± 2.1; mmHg; P Conclusion Despite higher O-GlcNAc levels in young population, we demonstrate that O-GlcNAc stimulation is able to improve pups’ response to endotoxemic shock. Our results show that it is the difference in O-GlcNAcylation between the basal levels and the post-stimulation levels that induces protection against septic shock.

Published
2021
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44. L’hydrocéphalie chronique de l’adulte et la dégénérescence lobaire fronto-temporale comportementale : une association plus que fortuite ?

Author

Edith Bigot-Corbel, Jesus Aguilar Garcia, Amandine Pallardy, Claire Boutoleau-Bretonnière, Hélène Pouclet-Courtemanche, and Philippe Damier

Subjects
Neurology, Neurology (clinical)
Abstract

Introduction L’association de l’hydrocephalie chronique de l’adulte (HCA) et de la degenerescence lobaire fronto-temporale comportementale (DLFTc) est peu rapportee dans la litterature. Objectifs Cette etude retrospective observationnelle vise a decrire cliniquement et radiologiquement (imageries morphologique et fonctionnelle) l’association DLFTc-HCA. Patients et methodes Parmi les patients vus en 2019 au CMRR de Nantes pour une DLFTc repondant aux criteres possible et probable de Rascovsky, nous avons recense ceux ayant egalement un diagnostic d’HCA. Le diagnostic d’HCA etait pose sur la triade de Hakim et l’imagerie (hydrocephalie associee a un effacement des sillons au vertex). Les imageries morphologiques et fonctionnelles ont ete comparees en aveugle avec 10 patients HCA sans DLFTc. Resultats Une HCA etait evoquee chez 9 des 81 patients DLFTc. Ils presentaient tous un trouble du controle executif cognitif et comportemental (Rascovsky ≥ 4/6) auquel s’ajoutaient des troubles de la marche, ameliores chez 7 des 8 patients ayant eu des ponctions lombaires soustractives, puis chez 1 des 2 patients derives. Huit DLFTc-HCA et 1 HCA avaient un gradient d’atrophie anteroposterieur, 3 des 9 DLFTc-HCA et aucun des 4 HCA ayant eu une imagerie fonctionnelle presentaient un hypometabolisme a predominance anterieure. Discussion Il s’agit a notre connaissance de la premiere serie clinique de patients DLFTc-HCA. L’absence de neuropathologie ou de genetique est la principale limite. L’atrophie a predominance anterieure chez 8 des 9 patients conforte cependant l’hypothese qu’il s’agit bien de DLFTc, et non de presentations comportementales d’HCA. La moindre detection d’un gradient en imagerie fonctionnelle pourrait etre due a l’hypometabolisme sous-cortical diffus. Conclusion L’association DLFTc-HCA n’est pas rare (11,1 % des DLFTc), et est a evoquer devant des troubles du comportement frontaux, des troubles de la marche, et une hydrocephalie sur l’imagerie.

Published
2020
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45. [Accreditation strategy for rare somatic molecular abnormalities detected or quantified by polymerase chain reaction: GBMHM recommendations]

Author

Pierre, Sujobert, Stéphanie, Dulucq, Anne Sophie, Alary, Pascaline, Etancelin, Anne, Bouvier, Lisa, Boureau, Aurélie, Chauveau, Olivier, Kosmider, Pascale, Flandrin, and Edith, Bigot-Corbel

Subjects
Quality Control, Societies, Scientific, medicine.medical_specialty, media_common.quotation_subject, education, DNA Mutational Analysis, Medical Oncology, Real-Time Polymerase Chain Reaction, Sensitivity and Specificity, Patient care, Accreditation, Gene Frequency, medicine, Humans, Medical physics, Quality (business), health care economics and organizations, media_common, business.industry, Reproducibility of Results, General Medicine, Single patient, Molecular Diagnostic Techniques, Hematologic Neoplasms, Practice Guidelines as Topic, France, business, Laboratories
Abstract

In 2020, accreditation of molecular tests according to ISO 15189 is a requirement for all French medical laboratories. For many years, the GBMHM group (French Group of Molecular Biologists in Hematology) supports this approach through organization of external quality evaluation campaigns, and by publishing recommendations that have allowed the accreditation of the most frequent molecular tests for most laboratories. However, some molecular abnormalities concerns very few patients (and sometimes a single patient), and therefore cannot be evaluated in the same way, because of the lack of external quality controls or inter-laboratory comparisons. In order to allow the accreditation of these rare analyzes, the GBMHM proposes recommendations, based on the fact that analyzes using the same methodology than those already accredited by an extensive validation process, may be accredited without the need for full analytical validation. In particular, assays based on quantitative PCR or endpoint PCR may be accredited after verification of primer specificity, repeatability and/or reproducibility, and the determination of detection or linearity limits. These recommendations, by defining the validation approach for rare molecular abnormalities, make it possible to extend the requirement of accreditation for rare tests, to provide the best patient care.

Published
2019

46. Frontotemporal dementia is the leading cause of 'true' A-/T+ profiles defined with Aβ

Author

Hélène, Pouclet-Courtemanche, Tri-Bao, Nguyen, Emilie, Skrobala, Claire, Boutoleau-Bretonnière, Florence, Pasquier, Elodie, Bouaziz-Amar, Edith, Bigot-Corbel, Susanna, Schraen, Julien, Dumurgier, Claire, Paquet, and Thibaud, Lebouvier

Subjects
Aβ42/40 ratio, Cerebrospinal fluid biomarkers, nutritional and metabolic diseases, Aβ42/Aβ40 ratio, Alzheimer's disease, Suspected non Alzheimer's disease pathology (SNAP), Frontotemporal dementia, nervous system diseases, CSF Biomarkers
Abstract

Introduction Patients with positive tauopathy but negative Aβ42 (A−T+) in the cerebrospinal fluid (CSF) represent a diagnostic challenge. The Aβ42/40 ratio supersedes Aβ42 and reintegrates “false” A−T+ patients into the Alzheimer's disease spectrum. However, the biomarker and clinical characteristics of “true” and “false” A−T+ patients remain elusive. Methods Among the 509 T+N+ patients extracted from the databases of three memory clinics, we analyzed T+N+ patients with normal Aβ42 and compared “false” A−T+ with abnormal Aβ42/40 ratio and “true” A−T+ patients with normal Aβ42/40 ratio, before CSF analysis and at follow-up. Results 24.9% of T+N+ patients had normal Aβ42 levels. Among them, 42.7% were “true” A−T+. “True” A−T+ had lower CSF tauP181 than “false” A−T+ patients. 48.0% of “true” A−T+ patients were diagnosed with frontotemporal lobar degeneration before CSF analysis and 64.0% at follow-up, as compared with 6% in the “false” A−T+ group (P, Highlights • Dementia with normal cerebrospinal fluid Aβ42 yet high cerebrospinal fluid tau181P is a situation referred to as A−T+N+ in the 2018 National Institute of Aging–Alzheimer's Association research framework. • The interpretation of A−T+N+ profiles is not consensual and uncomfortable for clinicians. • The use of Aβ42/40 ratio as a surrogate amyloid marker halves the number of uninformative A−T+N+ profiles. • T+N+ patients with normal Aβ42 yet abnormal Aβ42/40 have an Alzheimer's phenotype. • Frontotemporal lobar degeneration is probably the leading cause of A−T+N+ profiles.

Published
2019

47. O-GlcNAcylation blood levels are increased in response to stress induced by cardiopulmonary bypass

Author

A. Persello, Benjamin Lauzier, Angélique Erraud, Edith Bigot-Corbel, F. Souab, A. Maillard, T. Dupas, M. Ferreira, Bertrand Rozec, M. Denis, A. Blangy-Letheule, and C. Gaillard

Subjects
medicine.medical_specialty, business.industry, Organ dysfunction, Inflammation, Cardiac surgery, law.invention, surgical procedures, operative, law, Hemostasis, Internal medicine, Circulatory system, medicine, Cardiopulmonary bypass, Cardiology, medicine.symptom, Cardiology and Cardiovascular Medicine, business, Perfusion, Whole blood
Abstract

Introduction Cardiopulmonary bypass (CPB) is a common procedure to maintain body perfusion during cardiac surgery. It is associated with a systemic inflammatory response, hemostasis and circulatory dysfunction that can lead to organ dysfunction and seldomly to death. O-GlcNAcylation is a post-translational modification modulated in response to stress in different acute and chronic situations. Objective Decipher if blood O-GlcNAc levels are modified during CPB induced stress. Method Vingt adult patients with CPB time > 60 minutes were included. Blood samples were collected on EDTA at (i) anesthesia induction (Ind), (ii) aortic declamping (AD) and (iii) 5 hours post-declamping (AD + 5). Whole blood and plasma were recovered from samples. O-GlcNAc levels in blood were evaluated by western blot while plasmatic biological markers were measured on automatic laboratory analysis system to correlate O-GlcNAc level with systemic response to CPB. Demographics and One-Way ANOVA analysis were performed with RStudio. Results CPB induced an early increase of plasmatic inflammatory marker IL-6 (Ind: 5.7 ± 3.2, AD: 120.0 ± 26.5 pg/mL, P Conclusion In this preliminary study, we highlighted that the inflammation and tissue stress consecutive to CPB are associated with an increase in blood O-GlcNAc levels 5 hours after CPB. Inclusion of more patients and correlations between O-GlcNAc level variation and demographics and/or patients’ outcome might reveal a new biomarker of risk after CPB.

Published
2021
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48. O-GlcNAc stimulation is beneficial in sepsis in the young rat, involvement of the ATP-citrate lyase

Author

M. Denis, Benjamin Lauzier, T. Pele, M. De Waard, Didier Vertommen, Angélique Erraud, Edith Bigot-Corbel, Jérôme Montnach, Aurélia A. Leroux, Luc Bertrand, Bertrand Rozec, Arnaud Tessier, A. Persello, Justine Dontaine, Laurent Bultot, J. Dhot, Jacques Lebreton, Matthieu Rivière, and T. Dupas

Subjects
medicine.medical_specialty, Mean arterial pressure, ATP citrate lyase, business.industry, Septic shock, medicine.medical_treatment, Stimulation, Metabolism, medicine.disease, Sepsis, Endocrinology, Internal medicine, Shock (circulatory), medicine, medicine.symptom, Cardiology and Cardiovascular Medicine, business, Saline
Abstract

Introduction The young population, particularly at risk of septic shock, is rarely studied. The O-GlcNAcylation is a post-translational modification involved in cell survival, metabolism and stress response. We have shown that O-GlcNAc stimulation at the early phase of septic shock is beneficial in adult rats. Considering that O-GlcNAc levels are higher in the young, the impact of O-GlcNAc stimulation on sepsis in the young should be tested. Objective Evaluate if O-GlcNAc stimulation could improve sepsis outcomes in young. Method Endotoxemic shock was induced in 28 days old rats by injection of LPS (O111 :B4, 20 mg.kg−1–LPS) and compared to control rats (injection of saline–CTRL). One hour after LPS injection rats were randomly assigned to no therapy (LPS), fluidotherapy (saline, 10 mL.kg−1–LPS + R) ± NButGT (10 mg.kg−1–NButGT) to increase O-GlcNAc levels (n = 11 per group). Physiological functions and plasmatic markers were evaluated 2 hours later. Impact of treatment was evaluated with an adapted Pediatric RISk of Mortality score (PRISM score) and mortality was evaluated over 36 hours (n = 16 per group). Untargeted mass spectrometry was performed to identify cardiac O-GlcNAcylated proteins. Results LPS induced a shock (mean arterial pressure (MAP): CTRL: 67.2 ± 1.9; LPS: 50.7 ± 2.1 mmHg; P Conclusion O-GlcNAc stimulation acutely improves outcome in young septic shock rat. The impact of O-GlcNAcylation on ACLY is a potential issue to decipher the role of this protein during sepsis.

Published
2021
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49. Dosage des chaînes légères libres Kappa dans le LCS et apport de l’index Kappa selon la présence ou non de bandes oligoclonales d’IgG

Author

Pierre Olivier Bertho, Anne Hay-Lombardie, Guillaume Herbreteau, Edouard Le Carpentier, and Edith Bigot-Corbel

Subjects
Neurology, Neurology (clinical)
Abstract

Introduction Le dosage des chaines legeres libres Kappa dans le liquide cerebrospinal (LCS) et le calcul de l’index kappa semble apporter une aide interessante au diagnostic biologique de la sclerose en plaques. Objectifs Les etudes precedemment publiees fournissent des cut-offs variables pour le quotient Kappa et l’index Kappa. Nous presentons ici les resultats de l’application de ces differents cut-offs sur les resultats des mesures obtenues au laboratoire. Patients et methodes Nous avons mesure retrospectivement sur 236 couples serums-LCS les parametres suivants : albumine, IgG, IgA, IgM, chaines legeres libres Kappa et chaines legeres libres lambda. Tous les dosages ont ete realises sur Optilite® (Binding Site, Birmingham, Royaume-Uni) avec des reactifs dedies. Nous avons calcule les differents rapports et index. Parmi les 236 couples serums-LCS analyses, on retrouvait a l’IEF la presence de bandes oligoclonales (BOC) d’IgG dans 91 cas et l’absence de BOC dans 145 cas. Resultats Les resultats des dosages ont ete analyses selon la presence (BOC +) ou l’absence (BOC −) de synthese locale intrathecale d’IgG mise en evidence a l’IEF. On note des concentrations de chaines legeres Kappa, un quotient Kappa et surtout un index Kappa significativement plus eleve (p Discussion En appliquant pour l’index Kappa les differents cut-off de 2,9 ; 4,3 ou 5,8, nous obtenons une sensibilite variant de 100 % a 96 %, une specificite de 54 % a 71 %, une valeur predictive positive (VPP) variant de 86 % a 91 % et une valeur predictive negative (VPN) variant de 100 % a 87 %. Conclusion Dans notre etude le cut-off le plus sensible pour l’index IgG est celui determine par Valencia-Vera, c’est egalement celui qui nous fournit la meilleure VPN.

Published
2021
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50. Characteristics of monogenic versus polygenic familial hypobetalipoproteinemia

Author

Bertrand Cariou, X. Vanhoye, Edith Bigot-Corbel, Noël Peretti, G. Degraef, Matthieu Wargny, Antoine Rimbert, P.A. Rollat Farnier, Matthieu Pichelin, Alain Carrié, Didier Goxe, D. Coulibaly, René Valéro, Marie Marrec, Sybil Charrière, P. Moulin, and M. Di Filippo

Subjects
Genetics, business.industry, Familial Hypobetalipoproteinemia, Medicine, Cardiology and Cardiovascular Medicine, business
Published
2020
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