17 results on '"Fieschi, Claire"'
Search Results
2. Inherited human ZNF341 deficiency.
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Béziat V, Fieschi C, Momenilandi M, Migaud M, Belaid B, Djidjik R, and Puel A
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- Humans, Transcription Factors metabolism, Phenotype, STAT3 Transcription Factor genetics, STAT3 Transcription Factor metabolism, Mutation genetics, Immunoglobulin E, Job Syndrome genetics
- Abstract
Typical hyper-IgE syndromes (HIES) are caused by autosomal-dominant-negative (DN) variants of STAT3 (Signal Transducer And Activator Of Transcription 3) or IL6ST (Interleukin 6 Cytokine Family Signal Transducer), biallelic partial loss-of-function (LOF) variants of IL6ST, or biallelic complete LOF variants of ZNF341 (Zinc Finger Protein 341). Including the two new cases described in this review, only 20 patients with autosomal-recessive (AR) ZNF341 deficiency have ever been reported. Patients with AR ZNF341 deficiency have clinical and immunological phenotypes resembling those of patients with autosomal-dominant STAT3 deficiency, but with a usually milder clinical presentation and lower NK (Natural Killer) cell counts. ZNF341-deficient cells have 50% the normal level of STAT3 in the resting state. However, as there is no clear evidence that STAT3 haploinsufficiency causes HIES, this decrease alone is probably insufficient to explain the HIES phenotype observed in the ZNF341-deficient patients. The combination of decreased basal expression level and impaired autoinduction of STAT3 observed in ZNF341-deficient lymphocytes is considered a more likely pathophysiological mechanism. We review here what is currently known about the ZNF341 gene and ZNF341 deficiency, and briefly discuss possible roles for this protein in addition to its control of STAT3 activity., Competing Interests: Conflict of interest statement Nothing to declare., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2023
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3. Allogeneic stem cell transplantation compared to conservative management in adults with inborn errors of immunity.
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Cheminant M, Fox TA, Alligon M, Bouaziz O, Neven B, Moshous D, Blanche S, Guffroy A, Fieschi C, Malphettes M, Schleinitz N, Perlat A, Viallard JF, Dhedin N, Sarrot-Reynauld F, Durieu I, Humbert S, Fouyssac F, Barlogis V, Carpenter B, Hough R, Laurence A, Marçais A, Chakraverty R, Hermine O, Fischer A, Burns SO, Mahlaoui N, Morris EC, and Suarez F
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- Humans, Adult, Young Adult, Retrospective Studies, Conservative Treatment, Transplantation, Homologous methods, Stem Cell Transplantation methods, Transplantation Conditioning methods, Granulomatous Disease, Chronic therapy, Hematopoietic Stem Cell Transplantation methods, Graft vs Host Disease etiology
- Abstract
Allogeneic hematopoietic stem cell transplantation (alloSCT) is curative for severe inborn errors of immunity (IEIs), with recent data suggesting alloSCT in adulthood is safe and effective in selected patients. However, questions remain regarding the indications for and optimal timing of transplant. We retrospectively compared outcomes of transplanted vs matched nontransplanted adults with severe IEIs. Seventy-nine patients (aged ≥ 15 years) underwent alloSCT between 2008 and 2018 for IEIs such as chronic granulomatous disease (n = 20) and various combined immune deficiencies (n = 59). A cohort of nontransplanted patients from the French Centre de Référence Déficits Immunitaires Héréditaires registry was identified blindly for case-control analysis, with ≤3 matched controls per index patient, without replacement. The nontransplanted patients were matched for birth decade, age at last review greater than index patient age at alloSCT, chronic granulomatous disease or combined immune deficiencies, and autoimmune/lymphoproliferative complications. A total of 281 patients were included (79 transplanted, 202 nontransplanted). Median age at transplant was 21 years. Transplant indications were mainly lymphoproliferative disease (n = 23) or colitis (n = 15). Median follow-up was 4.8 years (interquartile range, 2.5-7.2). One-year transplant-related mortality rate was 13%. Estimated disease-free survival at 5 years was higher in transplanted patients (58% vs 33%; P = .007). Nontransplanted patients had an ongoing risk of severe events, with an increased mean cumulative number of recurrent events compared with transplanted patients. Sensitivity analyses removing patients with common variable immune deficiency and their matched transplanted patients confirm these results. AlloSCT prevents progressive morbidity associated with IEIs in adults, which may outweigh the negative impact of transplant-related mortality., (© 2023 by The American Society of Hematology.)
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- 2023
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4. Immune thrombocytopenia and pregnancy: an exposed/nonexposed cohort study.
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Guillet S, Loustau V, Boutin E, Zarour A, Comont T, Souchaud-Debouverie O, Costedoat Chalumeau N, Pan-Petesch B, Gobert D, Cheze S, Viallard JF, Morin AS, Sauvetre G, Cliquennois M, Royer B, Masseau A, Terriou L, Fieschi C, Lambotte O, Girault S, Lioger B, Audia S, Sacre K, Lega JC, Langlois V, Benachi A, Orvain C, Devidas A, Humbert S, Gambier N, Ruivard M, Zarrouk V, Ebbo M, Willems L, Segaux L, Mahevas M, Haddad B, Michel M, Canoui-Poitrine F, and Godeau B
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- Infant, Newborn, Female, Humans, Pregnancy, Cohort Studies, Prospective Studies, Retrospective Studies, Purpura, Thrombocytopenic, Idiopathic epidemiology, Purpura, Thrombocytopenic, Idiopathic therapy, Purpura, Thrombocytopenic, Idiopathic complications, Pregnancy Complications, Hematologic epidemiology, Pregnancy Complications, Hematologic therapy, Thrombocytopenia, Neonatal Alloimmune therapy
- Abstract
The risk of immune thrombocytopenia (ITP) worsening during pregnancy and neonatal ITP (NITP) have never been prospectively studied. We included 180 pregnant and 168 nonpregnant women with ITP in a prospective, multicenter, observational cohort study. A total of 131 pregnant women with ITP were matched to 131 nonpregnant women with ITP by history of splenectomy, ITP status (no response, response, complete response), and duration. Groups were followed for 15 months. The primary outcome was the first occurrence of ITP worsening defined by a composite end point including bleeding events and/or severe thrombocytopenia (<30 × 109/L) and/or ITP treatment modification. We also studied the recurrence of ITP worsening and the incidence of NITP and risk factors. The first occurrence of ITP worsening did not differ between pregnant and nonpregnant women with ITP (53.4 per 100 person-years [95% confidence interval {CI}, 40.8-69.9] vs 37.1 [95% CI, 27.5-50.0]; hazard ratio {HR}, 1.35 [95% CI, 0.89-2.03], P = .16). Pregnant women with ITP were more likely to have recurrence of severe thrombocytopenia and treatment modification (HR, 2.71 [95% CI, 1.41-5.23], P = .003; HR, 2.01 [95% CI, 1.14-3.57], P = .017, respectively). However, recurrence of severe bleeding events was not different between groups (P = .4). Nineteen (14%) neonates showed NITP <50 × 109/L. By multivariable analysis, NITP was associated with a previous offspring with NITP and maternal platelet count <50 × 109/L within 3 months before delivery (adjusted odds ratio, 5.55 [95% CI, 1.72-17.89], P = .004 and 4.07 [95% CI, 1.41-11.73], P = .009). To conclude, women with ITP do not increase their risk of severe bleeding during pregnancy. NITP is associated with NITP history and the severity of maternal ITP during pregnancy. These results will be useful for counseling women with ITP., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
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- 2023
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5. Mutations in the SRP54 gene cause severe congenital neutropenia as well as Shwachman-Diamond-like syndrome.
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Bellanné-Chantelot C, Schmaltz-Panneau B, Marty C, Fenneteau O, Callebaut I, Clauin S, Docet A, Damaj GL, Leblanc T, Pellier I, Stoven C, Souquere S, Antony-Debré I, Beaupain B, Aladjidi N, Barlogis V, Bauduer F, Bensaid P, Boespflug-Tanguy O, Berger C, Bertrand Y, Carausu L, Fieschi C, Galambrun C, Schmidt A, Journel H, Mazingue F, Nelken B, Quah TC, Oksenhendler E, Ouachée M, Pasquet M, Saada V, Suarez F, Pierron G, Vainchenker W, Plo I, and Donadieu J
- Subjects
- Adolescent, Adult, Apoptosis, Autophagy, Bone Marrow Diseases metabolism, Bone Marrow Diseases pathology, Child, Child, Preschool, Congenital Bone Marrow Failure Syndromes, Exocrine Pancreatic Insufficiency metabolism, Exocrine Pancreatic Insufficiency pathology, Female, Humans, Infant, Infant, Newborn, Lipomatosis metabolism, Lipomatosis pathology, Male, Middle Aged, Neutropenia genetics, Neutropenia metabolism, Neutropenia pathology, Shwachman-Diamond Syndrome, Up-Regulation, Young Adult, Bone Marrow Diseases genetics, Endoplasmic Reticulum Stress, Exocrine Pancreatic Insufficiency genetics, Lipomatosis genetics, Mutation, Neutropenia congenital, Signal Recognition Particle genetics
- Abstract
Congenital neutropenias (CNs) are rare heterogeneous genetic disorders, with about 25% of patients without known genetic defects. Using whole-exome sequencing, we identified a heterozygous mutation in the SRP54 gene, encoding the signal recognition particle (SRP) 54 GTPase protein, in 3 sporadic cases and 1 autosomal dominant family. We subsequently sequenced the SRP54 gene in 66 probands from the French CN registry. In total, we identified 23 mutated cases (16 sporadic, 7 familial) with 7 distinct germ line SRP54 mutations including a recurrent in-frame deletion (Thr117del) in 14 cases. In nearly all patients, neutropenia was chronic and profound with promyelocytic maturation arrest, occurring within the first months of life, and required long-term granulocyte colony-stimulating factor therapy with a poor response. Neutropenia was sometimes associated with a severe neurodevelopmental delay (n = 5) and/or an exocrine pancreatic insufficiency requiring enzyme supplementation (n = 3). The SRP54 protein is a key component of the ribonucleoprotein complex that mediates the co-translational targeting of secretory and membrane proteins to the endoplasmic reticulum (ER). We showed that SRP54 was specifically upregulated during the in vitro granulocytic differentiation, and that SRP54 mutations or knockdown led to a drastically reduced proliferation of granulocytic cells associated with an enhanced P53-dependent apoptosis. Bone marrow examination of SRP54 -mutated patients revealed a major dysgranulopoiesis and features of cellular ER stress and autophagy that were confirmed using SRP54 -mutated primary cells and SRP54 knockdown cells. In conclusion, we characterized a pathological pathway, which represents the second most common cause of CN with maturation arrest in the French CN registry., (© 2018 by The American Society of Hematology.)
- Published
- 2018
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6. Autoimmune cytopenias associated with inflammatory bowel diseases: Insights from a multicenter retrospective cohort.
- Author
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Uzzan M, Galicier L, Gornet JM, Oksenhendler E, Fieschi C, Allez M, Bouhnik Y, Kirchgesner J, Boutboul D, Treton X, Gérard L, Mahévas M, Cosnes J, and Amiot A
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- Adolescent, Adult, Anemia, Hemolytic, Autoimmune therapy, Case-Control Studies, Child, Female, France, Humans, Incidence, Infliximab therapeutic use, Male, Middle Aged, Registries, Retrospective Studies, Rituximab therapeutic use, Thrombocytopenia therapy, Young Adult, Anemia, Hemolytic, Autoimmune epidemiology, Inflammatory Bowel Diseases classification, Inflammatory Bowel Diseases complications, Inflammatory Bowel Diseases therapy, Thrombocytopenia epidemiology
- Abstract
Introduction: Autoimmune cytopenias (AIC) including autoimmune hemolytic anemia (AIHA) and immunologic thrombocytopenia (ITP) are rare immunologic disorders, scarcely reported in inflammatory bowel diseases (IBD). We conducted a multicentric retrospective study, including a case-control analysis, that aimed to describe the characteristics and outcomes of patients affected by AIC and IBD., Method: Forty cases were recruited from 4 IBD centers and 2 AIC tertiary centers. Controls were recruited from the MICISTA registry., Results: From the MICISTA registry, incidences were estimated at 4.1/100,000 patient-years and 12.5/100,000 patient-years after IBD diagnosis for AIHA and ITP, respectively. All AIHA patients (n=14) had colonic involvement (13/14 with UC), whereas CD (52%) and UC (48%) diagnoses were evenly distributed among ITP patients. Compared to control IBD patients, cases were characterized by a higher frequency of extra-intestinal manifestations (37.5% vs 17%, p<0.001) and by the presence of IBD severity's hallmark. AIHA and IBD ran mainly in parallel, and 12 out of 14 AIHA were warm AIHA. In isolated cases, rituximab and infliximab were efficient to treat IBD and AIC, respectively. IBD surgery may induce AIC remission in some cases., Conclusion: Although low, incidence of AIC appears higher in IBD patients compared to the general population. The association seems to be mainly non-fortuitous, especially for colitis-associated AIHA., (Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2017
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7. iNKT and memory B-cell alterations in HHV-8 multicentric Castleman disease.
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Sbihi Z, Dossier A, Boutboul D, Galicier L, Parizot C, Emarre A, Hoareau B, Dupin N, Marcelin AG, Oudin A, Fieschi C, Agbalika F, Autran B, Oksenhendler E, and Carcelain G
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- Adult, Aged, Aged, 80 and over, Antigens, CD1d analysis, B-Lymphocyte Subsets virology, Cell Proliferation, Female, Humans, Immunoglobulin D analysis, Male, Middle Aged, Natural Killer T-Cells virology, Sarcoma, Kaposi pathology, Sarcoma, Kaposi virology, Spleen pathology, Spleen virology, Tumor Necrosis Factor Receptor Superfamily, Member 7 analysis, B-Lymphocyte Subsets pathology, Castleman Disease pathology, Castleman Disease virology, Herpesvirus 8, Human isolation & purification, Natural Killer T-Cells pathology
- Abstract
Human herpesvirus 8 (HHV-8) is the causative agent of Kaposi sarcoma (KS) and multicentric Castleman disease (MCD), a life-threatening, virally induced B-cell lymphoproliferative disorder. HHV-8 is a B-lymphotropic γ-herpesvirus closely related to the Epstein-Barr virus (EBV). Invariant natural killer T (iNKT) cells are innate-like T cells that play a role in antiviral immunity, specifically in controlling viral replication in EBV-infected B cells. Decline of iNKT cells is associated with age or HIV infection, both situations associated with HHV-8-related diseases. We analyzed iNKT cells in both blood (n = 26) and spleen (n = 9) samples from 32 patients with HHV-8 MCD and compared them with patients with KS (n = 24) and healthy donors (n = 29). We determined that both circulating and splenic iNKT cell frequencies were markedly decreased in patients with HHV-8 MCD and were undetectable in 6 of them. Moreover, iNKT cells from patients with HHV-8 MCD displayed a proliferative defect after stimulation with α-galactosylceramide. These iNKT cell alterations were associated with an imbalance in B-cell subsets, including a significant decrease in memory B cells, particularly of marginal zone (MZ) B cells. Coculture experiments revealed that the decrease in iNKT cells contributed to the alterations in the B-cell subset distribution. These observations contribute to a better understanding of the complex interactions between HHV-8 and immune cells that cause HHV-8-related MCD., (© 2017 by The American Society of Hematology.)
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- 2017
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8. High frequency of fatal haemophagocytic lymphohistiocytosis syndrome in enteropathy-associated T cell lymphoma.
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Amiot A, Allez M, Treton X, Fieschi C, Galicier L, Joly F, Gornet JM, Oksenhendler E, Lémann M, and Bouhnik Y
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- Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols adverse effects, Cladribine administration & dosage, Disease Progression, Disease-Free Survival, Enteropathy-Associated T-Cell Lymphoma complications, Enteropathy-Associated T-Cell Lymphoma surgery, Female, Humans, Kaplan-Meier Estimate, Lymphohistiocytosis, Hemophagocytic complications, Lymphohistiocytosis, Hemophagocytic surgery, Male, Middle Aged, Neutropenia etiology, Purine Nucleotides adverse effects, Retrospective Studies, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Enteropathy-Associated T-Cell Lymphoma drug therapy, Lymphohistiocytosis, Hemophagocytic drug therapy, Purine Nucleotides therapeutic use
- Abstract
Introduction: Enteropathy-associated T-cell lymphoma is a rare form of T-cell lymphoma associated with a poor prognosis and the relative ineffectiveness of standard chemotherapy. The occurrence of haemophagocytic lymphohistiocytosis has been reported only once with this entity., Patients and Methods: A retrospective study of 15 patients with enteropathy-associated T-cell lymphoma (type 1 in 12), followed-up in our units, since 1985. Two patients died before starting chemotherapy. The remaining 13 patients were treated with standard chemotherapy (n=7) and purine nucleotide analogues (n=6)., Results: Median follow-up was 8.7 (1-97) months. Surgery was required in 10 patients (66%) for intestinal complications (n=7) or elective small bowel resection (n=3). Survival probability was 40% and 20% at 1 and 5 years, respectively (Kaplan-Meier method). Survival was not significantly different between the two chemotherapy regimens. However, a slight decrease of febrile neutropenia was observed in the purine nucleotide analogues group (p=0.06). Haemophagocytic lymphohistiocytosis occurred in 6/15 (40%) cases. In these six patients, haemophagocytic lymphohistiocytosis was always fatal within 3 months., Conclusion: Enteropathy-associated T-cell lymphoma is associated with a poor outcome, independently of the chemotherapy regimens administered and frequent occurrence of haemophagocytic lymphohistiocytosis. The latter complication should be considered for urgent rescue therapy., (Copyright © 2011 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2012
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9. Rituximab decreases the risk of lymphoma in patients with HIV-associated multicentric Castleman disease.
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Gérard L, Michot JM, Burcheri S, Fieschi C, Longuet P, Delcey V, Meignin V, Agbalika F, Chevret S, Oksenhendler E, and Galicier L
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- Adult, Antibodies, Monoclonal, Murine-Derived adverse effects, Antineoplastic Agents adverse effects, Antineoplastic Agents therapeutic use, Castleman Disease complications, Female, Follow-Up Studies, Humans, Logistic Models, Male, Middle Aged, Outcome Assessment, Health Care statistics & numerical data, Proportional Hazards Models, Retrospective Studies, Risk Factors, Rituximab, Sarcoma, Kaposi chemically induced, Survival Analysis, Antibodies, Monoclonal, Murine-Derived therapeutic use, Castleman Disease drug therapy, HIV Infections complications, Lymphoma, Non-Hodgkin prevention & control
- Abstract
HIV-associated multicentric Castleman disease (MCD) is associated with a high risk of developing non-Hodgkin lymphoma (NHL). Rituximab is effective in HIV-MCD, but its impact on NHL incidence remains unknown. From a single-center prospective cohort, 113 patients were identified with a diagnosis of HIV-MCD for the present study. To compare the incidence of NHL between patients who had received a rituximab-based treatment (R+ group) and those who had not (R- group), data were analyzed before and after matching on propensity scores and after multiple imputation. The mean follow-up was 4.2 years. In the R- group (n = 65), 17 patients developed NHL (incidence, 69.6 of 1000 person years). In the R+ group (n = 48), only 1 patient developed NHL (incidence, 4.2 of 1000 person years). Based on the propensity score-matching method, a significant decrease in the incidence of NHL was observed in patients who had been treated with rituximab (hazard ratio, 0.09; 95% confidence interval, 0.01-0.70). Ten Kaposi sarcoma (KS) exacerbations and 1 newly diagnosed KS were observed in 9 patients after rituximab therapy. Rituximab was associated with an 11-fold lower risk of developing lymphoma. KS exacerbation was the most challenging adverse event after rituximab therapy.
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- 2012
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10. Cutaneous tumor lysis syndrome in a patient with HTLV-1 adult T-cell lymphoma/leukemia.
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Bouaziz JD, Cordel N, Hickman G, Fieschi C, Ortonne N, and Bagot M
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- Antineoplastic Combined Chemotherapy Protocols adverse effects, Apoptosis drug effects, Humans, Leukemia-Lymphoma, Adult T-Cell drug therapy, Male, Middle Aged, Skin Diseases etiology, Tumor Lysis Syndrome etiology, Leukemia-Lymphoma, Adult T-Cell pathology, Skin Diseases pathology, Tumor Lysis Syndrome pathology
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- 2009
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11. FAS-L, IL-10, and double-negative CD4- CD8- TCR alpha/beta+ T cells are reliable markers of autoimmune lymphoproliferative syndrome (ALPS) associated with FAS loss of function.
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Magerus-Chatinet A, Stolzenberg MC, Loffredo MS, Neven B, Schaffner C, Ducrot N, Arkwright PD, Bader-Meunier B, Barbot J, Blanche S, Casanova JL, Debré M, Ferster A, Fieschi C, Florkin B, Galambrun C, Hermine O, Lambotte O, Solary E, Thomas C, Le Deist F, Picard C, Fischer A, and Rieux-Laucat F
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- Adolescent, Adult, Autoimmune Diseases blood, Autoimmune Diseases genetics, Autoimmune Diseases metabolism, Biomarkers blood, Biomarkers metabolism, CD4 Antigens blood, CD4 Antigens metabolism, CD8 Antigens blood, CD8 Antigens metabolism, Case-Control Studies, Child, Child, Preschool, Fas Ligand Protein blood, Humans, Infant, Infant, Newborn, Interleukin-10 blood, Lymphoproliferative Disorders blood, Lymphoproliferative Disorders genetics, Lymphoproliferative Disorders metabolism, Middle Aged, Mutation physiology, Syndrome, T-Lymphocytes pathology, Young Adult, fas Receptor physiology, Autoimmune Diseases diagnosis, Fas Ligand Protein metabolism, Interleukin-10 metabolism, Lymphoproliferative Disorders diagnosis, Receptors, Antigen, T-Cell, alpha-beta metabolism, T-Lymphocytes metabolism, fas Receptor genetics
- Abstract
Autoimmune lymphoproliferative syndrome (ALPS) is characterized by splenomegaly, lymphadenopathy, hypergammaglobulinemia, accumulation of double-negative TCRalphabeta(+) CD4(-)CD8(-) T cells (DNT cells), and autoimmunity. Previously, DNT cell detection and a functional defect of T cells in a FAS-induced apoptosis test in vitro had been used for ALPS diagnosis. However, a functional defect can also be detected in mutation-positive relatives (MPRs) who remain free of any ALPS-related disease. In contrast, lymphocytes from patients carrying a somatic mutation of FAS exhibit normal sensitivity to FAS-induced apoptosis in vitro. We assessed the soluble FAS-L concentration in the plasma of ALPS patients carrying FAS mutations. Overall, we showed that determination of the FAS-L represents, together with the IL-10 concentration and the DNT cell percentage, a reliable tool for the diagnosis of ALPS.
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- 2009
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12. Dasatinib-induced lupus.
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Rea D, Bergeron A, Fieschi C, Bengoufa D, Oksenhendler E, and Dombret H
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- Aged, Autoimmunity immunology, Dasatinib, Female, Humans, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Lupus Erythematosus, Systemic immunology, Protein Kinase Inhibitors therapeutic use, Pyrimidines therapeutic use, Thiazoles therapeutic use, Autoantibodies isolation & purification, Autoimmunity drug effects, Lupus Erythematosus, Systemic chemically induced, Protein Kinase Inhibitors adverse effects, Pyrimidines adverse effects, Thiazoles adverse effects
- Published
- 2008
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13. Common variable immunodeficiency disorders: division into distinct clinical phenotypes.
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Chapel H, Lucas M, Lee M, Bjorkander J, Webster D, Grimbacher B, Fieschi C, Thon V, Abedi MR, and Hammarstrom L
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- Age of Onset, Autoimmunity, CD8-Positive T-Lymphocytes immunology, Cohort Studies, Common Variable Immunodeficiency complications, Common Variable Immunodeficiency mortality, Common Variable Immunodeficiency pathology, Humans, Immunoglobulin Isotypes blood, Leukemic Infiltration, Phenotype, Prognosis, Registries, Common Variable Immunodeficiency classification
- Abstract
The European Common Variable Immunodeficiency Disorders registry was started in 1996 to define distinct clinical phenotypes and determine overlap within individual patients. A total of 7 centers contributed patient data, resulting in the largest cohort yet reported. Patients (334), validated for the diagnosis, were followed for an average of 25.6 years (9461 patient-years). Data were used to define 5 distinct clinical phenotypes: no complications, autoimmunity, polyclonal lymphocytic infiltration, enteropathy, and lymphoid malignancy. A total of 83% of patients had only one of these phenotypes. Analysis of mortality showed a considerable reduction in the last 15 years and that different phenotypes were associated with different survival times. Types of complications and clinical phenotypes varied significantly between countries, indicating the need for large, international registries. Ages at onset of symptoms and diagnosis were shown to have a Gaussian distribution, but were not useful predictors of phenotype. The only clinical predictor was polyclonal lymphocytic infiltration, which was associated with a 5-fold increased risk of lymphoid malignancy. There was widespread variation in the levels of serum immunoglobulin isotypes as well as in the percentages and absolute numbers of B cells, confirming the heterogeneity of these conditions. Higher serum IgM and lower circulating CD8 proportions were found to be predictive markers for polyclonal lymphocytic infiltration and autoimmunity, respectively.
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- 2008
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14. A role for interleukin-12/23 in the maturation of human natural killer and CD56+ T cells in vivo.
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Guia S, Cognet C, de Beaucoudrey L, Tessmer MS, Jouanguy E, Berger C, Filipe-Santos O, Feinberg J, Camcioglu Y, Levy J, Al Jumaah S, Al-Hajjar S, Stephan JL, Fieschi C, Abel L, Brossay L, Casanova JL, and Vivier E
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- Adolescent, Adult, Child, Child, Preschool, Disease Susceptibility, Female, Humans, Immunologic Memory, Interleukin-12 Subunit p40 deficiency, Male, Mutation, Mycobacterium Infections immunology, Receptors, Interleukin-12 deficiency, Receptors, Interleukin-12 genetics, Salmonella Infections immunology, T-Lymphocytes immunology, CD56 Antigen, Interleukin-12 physiology, Interleukin-23 physiology, Killer Cells, Natural immunology
- Abstract
Natural killer (NK) cells have been originally defined by their "naturally occurring" effector function. However, only a fraction of human NK cells is reactive toward a panel of prototypical tumor cell targets in vitro, both for the production of interferon-gamma (IFN-gamma) and for their cytotoxic response. In patients with IL12RB1 mutations that lead to a complete IL-12Rbeta1 deficiency, the size of this naturally reactive NK cell subset is diminished, in particular for the IFN-gamma production. Similar data were obtained from a patient with a complete deficit in IL-12p40. In addition, the size of the subset of effector memory T cells expressing CD56 was severely decreased in IL-12Rbeta1- and IL-12p40-deficient patients. Human NK cells thus require in vivo priming with IL-12/23 to acquire their full spectrum of functional reactivity, while T cells are dependent upon IL-12/23 signals for the differentiation and/or the maintenance of CD56(+) effector memory T cells. The susceptibility of IL-12/23 axis-deficient patients to Mycobacterium and Salmonella infections in combination with the absence of mycobacteriosis or salmonellosis in the rare cases of human NK cell deficiencies point to a role for CD56(+) T cells in the control of these infections in humans.
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- 2008
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15. The human spleen is a major reservoir for long-lived vaccinia virus-specific memory B cells.
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Mamani-Matsuda M, Cosma A, Weller S, Faili A, Staib C, Garçon L, Hermine O, Beyne-Rauzy O, Fieschi C, Pers JO, Arakelyan N, Varet B, Sauvanet A, Berger A, Paye F, Andrieu JM, Michel M, Godeau B, Buffet P, Reynaud CA, and Weill JC
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- Case-Control Studies, Humans, Immunoglobulin G, Spleen immunology, Splenectomy, B-Lymphocytes immunology, B-Lymphocytes virology, Immunologic Memory, Spleen cytology, Vaccinia virus immunology
- Abstract
The fact that you can vaccinate a child at 5 years of age and find lymphoid B cells and antibodies specific for this vaccination 70 years later remains an immunologic enigma. It has never been determined how these long-lived memory B cells are maintained and whether they are protected by storage in a special niche. We report that, whereas blood and spleen compartments present similar frequencies of IgG(+) cells, antismallpox memory B cells are specifically enriched in the spleen where they account for 0.24% of all IgG(+) cells (ie, 10-20 million cells) more than 30 years after vaccination. They represent, in contrast, only 0.07% of circulating IgG(+) B cells in blood (ie, 50-100,000 cells). An analysis of patients either splenectomized or rituximab-treated confirmed that the spleen is a major reservoir for long-lived memory B cells. No significant correlation was observed between the abundance of these cells in blood and serum titers of antivaccinia virus antibodies in this study, including in the contrasted cases of B cell-depleting treatments. Altogether, these data provide evidence that in humans, the two arms of B-cell memory--long-lived memory B cells and plasma cells--have specific anatomic distributions--spleen and bone marrow--and homeostatic regulation.
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- 2008
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16. Intensive chemotherapy regimen (LMB86) for St Jude stage IV AIDS-related Burkitt lymphoma/leukemia: a prospective study.
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Galicier L, Fieschi C, Borie R, Meignin V, Daniel MT, Gérard L, and Oksenhendler E
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- Adult, Antiretroviral Therapy, Highly Active, Burkitt Lymphoma mortality, Burkitt Lymphoma pathology, CD4 Lymphocyte Count, Cyclophosphamide administration & dosage, Cytarabine administration & dosage, Disease-Free Survival, Doxorubicin administration & dosage, Etoposide administration & dosage, Female, Humans, Kaplan-Meier Estimate, Lymphoma, AIDS-Related mortality, Lymphoma, AIDS-Related pathology, Male, Methotrexate administration & dosage, Middle Aged, Neoplasm Staging, Prednisone administration & dosage, Prognosis, Prospective Studies, Treatment Outcome, Vincristine administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Burkitt Lymphoma drug therapy, Lymphoma, AIDS-Related drug therapy
- Abstract
Prognosis of acquired immunodeficiency syndrome (AIDS)-related non-Hodgkin lymphoma has improved since the introduction of highly active antiretroviral therapy. Burkitt lymphomas (BLs) still have poor outcome in patients with bone marrow (BM) or central nervous system (CNS) involvement when treated with standard-dose chemotherapy. We have prospectively evaluated the LMB86 regimen in 63 human immunodeficiency virus (HIV)-infected patients with stage IV (BM and/or CNS involvement) BL consecutively recruited between November 1992 and January 2006. At BL diagnosis, the median CD4 cell count was 239 x 10(6)/L (range, 16-1188 x 10(6)/L). BM and CNS involvement were present in 55 (80%) and 48 (76%) patients, respectively. Forty-four patients (70%) achieved complete response. Seven treatment-related deaths occurred and all patients experienced severe BM toxicity. With a median follow-up of 66 months (range, 6-165 months), 11 patients relapsed. The estimate 2-year overall survival and disease-free survival were 47.1% (95% CI, 34-59.1) and 67.8% (95% CI, 51-80), respectively. We identified 2 poor prognosis factors: low CD4 count and ECOG more than 2. Patients with 0 or 1 factor had good outcome (2-year survival: 60%) contrasting with patients with 2 factors (2-year survival: 12%). We conclude that LMB86 regimen is highly effective in advanced HIV-related BL and should be proposed for patients with CD4 count higher than 200 x 10(6)/L or ECOG of 2 or less.
- Published
- 2007
- Full Text
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17. A novel form of complete IL-12/IL-23 receptor beta1 deficiency with cell surface-expressed nonfunctional receptors.
- Author
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Fieschi C, Bosticardo M, de Beaucoudrey L, Boisson-Dupuis S, Feinberg J, Santos OF, Bustamante J, Levy J, Candotti F, and Casanova JL
- Subjects
- Antibodies, Monoclonal chemistry, Cells, Cultured, Child, Cytokines metabolism, DNA, Complementary metabolism, DNA-Binding Proteins metabolism, Enzyme-Linked Immunosorbent Assay, Exons, Flow Cytometry, Gene Deletion, Gene Transfer Techniques, Humans, Interferon-gamma metabolism, Interleukin-12 metabolism, Interleukin-23, Interleukin-23 Subunit p19, Killer Cells, Natural metabolism, Male, Models, Genetic, Mutation, Open Reading Frames, Phenotype, Phosphorylation, Polymerase Chain Reaction, Protein Folding, Protein Structure, Tertiary, RNA metabolism, Receptors, Interleukin deficiency, Receptors, Interleukin-12, Retroviridae genetics, STAT4 Transcription Factor, Time Factors, Trans-Activators metabolism, Cell Membrane metabolism, Interleukins metabolism, Receptors, Interleukin metabolism
- Abstract
Complete interleukin-12/interleukin-23 receptor beta1 (IL-12Rbeta1) deficiency is the most frequent known genetic etiology of the syndrome of Mendelian susceptibility to mycobacterial disease. The patients described to date lack IL-12Rbeta1 at the surface of their natural killer (NK) and T cells due to IL12RB1 mutations, which either interrupt the open reading frame or disrupt protein folding. We describe a patient with a large in-frame deletion of 12165 nucleotides (nt) in IL12RB1, encompassing exons 8 to 13 and resulting in the surface expression of nonfunctional IL-12Rbeta1. These 6 exons encode the proximal NH2-terminal half of the extracellular domain downstream from the cytokine-binding domain. Five of 6 monoclonal anti-IL-12Rbeta1 antibodies tested recognized the internally truncated chain on the cell surface. However, IL-12 and IL-23 did not bind normally to the patient's IL-12Rbeta1-containing respective heterodimeric receptors. As a result, signal transducer and activator of transcription-4 (STAT4) was not phosphorylated and interferon-gamma (IFN-gamma) production was not induced in the patient's cells upon stimulation with even high doses of IL-12 or IL-23. The functional defect was completely rescued by retrovirus-mediated IL-12Rbeta1 gene transfer. Thus, the detection of IL-12Rbeta1 on the cell surface does not exclude the possibility of complete IL-12Rbeta1 deficiency in patients with mycobacteriosis or salmonellosis. Paradoxically, the largest IL12RB1 mutation detected is associated with the cell surface expression of nonfunctional IL-12Rbeta1, defining a novel genetic form of IL-12Rbeta1 deficiency.
- Published
- 2004
- Full Text
- View/download PDF
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