11 results on '"Artal, E"'
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2. Immune dysregulation is an important factor in the underlying complications in Influenza infection. ApoH, IL-8 and IL-15 as markers of prognosis.
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Garcinuño S, Lalueza A, Gil-Etayo FJ, Díaz-Simón R, Lizasoain I, Moraga A, Diaz-Benito B, Naranjo L, Cabrera-Marante O, Pleguezuelo DE, Ruiz-Ruigomez M, Ayuso B, Arrieta E, Folgueira D, Paz-Artal E, Cueto C, Lumbreras C, Serrano A, and Serrano M
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- Humans, Male, Female, Prognosis, Middle Aged, Aged, Prospective Studies, Adult, Influenza, Human immunology, Influenza, Human blood, Biomarkers blood, Interleukin-15 blood, Interleukin-8 blood
- Abstract
Introduction: Influenza virus infection can cause a range of clinical symptoms, including respiratory failure (RF) and even death. The mechanisms responsible for the most severe forms of the disease are not yet well understood. The objective is to assess the initial immune response upon admission and its potential impact on infection progression., Methods: We conducted a prospective observational study of patients with influenza virus infection who required admission to a tertiary hospital in the 2017/18 and 2018/19 flu seasons. Immune markers, surrogate markers of neutrophil activation, and blood levels of DNase I and Apolipoprotein-H (ApoH) were determined in the first serum sample available during hospital care. Patients were followed until hospital discharge or death. Initially, 792 patients were included. From this group, 107 patients with poor evolution were selected, and a random control group was matched by day of admission., Results: Patients with poor outcomes had significantly reduced ApoH levels, a soluble protein that regulate both complement and coagulation pathways. In multivariate analysis, low plasma levels of ApoH (OR:5.43; 2.21-13.4), high levels of C- reactive protein (OR:2.73: 1.28-5.4), hyperferritinemia (OR:2.83; 1.28-5.4) and smoking (OR:3.41; 1.04-11.16), were significantly associated with a worse prognosis. RF was independently associated with low levels of ApoH (OR: 5.12; 2.02-1.94), while high levels of IL15 behaved as a protective factor (OR:0.30; 0.12-0.71)., Discussion: Therefore, in hospitalized influenza patients, a dysregulated early immune response is associated with a worse outcome. Adequate plasma levels of ApoH are protective against severe influenza and RF and High levels of IL15 protect against RF., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Garcinuño, Lalueza, Gil-Etayo, Díaz-Simón, Lizasoain, Moraga, Diaz-Benito, Naranjo, Cabrera-Marante, Pleguezuelo, Ruiz-Ruigomez, Ayuso, Arrieta, Folgueira, Paz-Artal, Cueto, Lumbreras, Serrano and Serrano.)
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- 2024
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3. Decreased breadth of the antibody response to the spike protein of SARS-CoV-2 after repeated vaccination.
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Horndler L, Delgado P, Romero-Pinedo S, Quesada M, Balabanov I, Laguna-Goya R, Almendro-Vázquez P, Llamas MA, Fresno M, Paz-Artal E, van Santen HM, Álvarez-Fernández S, Olmo A, and Alarcón B
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- Humans, Antibody Formation, BNT162 Vaccine, COVID-19 Vaccines, ChAdOx1 nCoV-19, Spike Glycoprotein, Coronavirus, Vaccination, Antibodies, SARS-CoV-2, COVID-19 prevention & control
- Abstract
Introduction: The rapid development of vaccines to prevent COVID-19 has raised the need to compare the capacity of different vaccines in terms of developing a protective humoral response. Previous studies have shown inconsistent results in this area, highlighting the importance of further research to evaluate the efficacy of different vaccines., Methods: This study utilized a highly sensitive and reliable flow cytometry method to measure the titers of IgG1 isotype antibodies in the blood of healthy volunteers after receiving one or two doses of various vaccines administered in Spain. The method was also used to simultaneously measure the reactivity of antibodies to the S protein of the original Wuhan strain and variants B.1.1.7 (Alpha), B.1.617.2 (Delta), and B.1.617.1 (Kappa)., Results: Significant differences were observed in the titer of anti-S antibodies produced after a first dose of the vaccines ChAdOx1 nCov-19/AstraZeneca, mRNA-1273/Moderna, BNT162b2/Pfizer-BioNTech, and Ad26.COV.S/Janssen. Furthermore, a relative reduction in the reactivity of the sera with the Alpha, Delta, and Kappa variants, compared to the Wuhan strain, was observed after the second boosting immunization., Discussion: The findings of this study provide a comparison of different vaccines in terms of anti-S antibody generation and cast doubts on the convenience of repeated immunization with the same S protein sequence. The multiplexed capacity of the flow cytometry method utilized in this study allowed for a comprehensive evaluation of the efficacy of various vaccines in generating a protective humoral response. Future research could focus on the implications of these findings for the development of effective COVID-19 vaccination strategies., Competing Interests: The authors have issued a patent application owned by CSIC., (Copyright © 2023 Horndler, Delgado, Romero-Pinedo, Quesada, Balabanov, Laguna-Goya, Almendro-Vázquez, Llamas, Fresno, Paz-Artal, van Santen, Álvarez-Fernández, Olmo and Alarcón.)
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- 2023
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4. Defending against SARS-CoV-2: The T cell perspective.
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Almendro-Vázquez P, Laguna-Goya R, and Paz-Artal E
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- Animals, Adjuvants, Immunologic, Adjuvants, Pharmaceutic, Antibodies, Humans, CD8-Positive T-Lymphocytes, COVID-19 immunology, SARS-CoV-2
- Abstract
SARS-CoV-2-specific T cell response has been proven essential for viral clearance, COVID-19 outcome and long-term memory. Impaired early T cell-driven immunity leads to a severe form of the disease associated with lymphopenia, hyperinflammation and imbalanced humoral response. Analyses of acute SARS-CoV-2 infection have revealed that mild COVID-19 course is characterized by an early induction of specific T cells within the first 7 days of symptoms, coordinately followed by antibody production for an effective control of viral infection. In contrast, patients who do not develop an early specific cellular response and initiate a humoral immune response with subsequent production of high levels of antibodies, develop severe symptoms. Yet, delayed and persistent bystander CD8+ T cell activation has been also reported in hospitalized patients and could be a driver of lung pathology. Literature supports that long-term maintenance of T cell response appears more stable than antibody titters. Up to date, virus-specific T cell memory has been detected 22 months post-symptom onset, with a predominant IL-2 memory response compared to IFN-γ. Furthermore, T cell responses are conserved against the emerging variants of concern (VoCs) while these variants are mostly able to evade humoral responses. This could be partly explained by the high HLA polymorphism whereby the viral epitope repertoire recognized could differ among individuals, greatly decreasing the likelihood of immune escape. Current COVID-19-vaccination has been shown to elicit Th1-driven spike-specific T cell response, as does natural infection, which provides substantial protection against severe COVID-19 and death. In addition, mucosal vaccination has been reported to induce strong adaptive responses both locally and systemically and to protect against VoCs in animal models. The optimization of vaccine formulations by including a variety of viral regions, innovative adjuvants or diverse administration routes could result in a desirable enhanced cellular response and memory, and help to prevent breakthrough infections. In summary, the increasing evidence highlights the relevance of monitoring SARS-CoV-2-specific cellular immune response, and not only antibody levels, as a correlate for protection after infection and/or vaccination. Moreover, it may help to better identify target populations that could benefit most from booster doses and to personalize vaccination strategies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Almendro-Vázquez, Laguna-Goya and Paz-Artal.)
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- 2023
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5. Cellular and humoral immune responses and breakthrough infections after three SARS-CoV-2 mRNA vaccine doses.
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Almendro-Vázquez P, Chivite-Lacaba M, Utrero-Rico A, González-Cuadrado C, Laguna-Goya R, Moreno-Batanero M, Sánchez-Paz L, Luczkowiak J, Labiod N, Folgueira MD, Delgado R, and Paz-Artal E
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- Antibodies, Neutralizing, Antibodies, Viral, BNT162 Vaccine, COVID-19 Vaccines, Humans, Immunity, Humoral, Pandemics, SARS-CoV-2, Vaccines, Synthetic, mRNA Vaccines, COVID-19 prevention & control, Viral Vaccines
- Abstract
Background: SARS-CoV-2 vaccination has proven the most effective measure to control the COVID-19 pandemic. Booster doses are being administered with limited knowledge on their need and effect on immunity., Objective: To determine the duration of specific T cells, antibodies and neutralization after 2-dose vaccination, to assess the effect of a third dose on adaptive immunity and to explore correlates of protection against breakthrough infection., Methods: 12-month longitudinal assessment of SARS-CoV-2-specific T cells, IgG and neutralizing antibodies triggered by 2 BNT162b2 doses followed by a third mRNA-1273 dose in a cohort of 77 healthcare workers: 17 with SARS-CoV-2 infection prior to vaccination (recovered) and 60 naïve., Results: Peak levels of cellular and humoral response were achieved 2 weeks after the second dose. Antibodies declined thereafter while T cells reached a plateau 3 months after vaccination. The decline in neutralization was specially marked in naïve individuals and it was this group who benefited most from the third dose, which resulted in a 20.9-fold increase in neutralization. Overall, recovered individuals maintained higher levels of T cells, antibodies and neutralization 1 to 6 months post-vaccination than naïve. Seventeen asymptomatic or mild SARS-CoV-2 breakthrough infections were reported during follow-up, only in naïve individuals. This viral exposure boosted adaptive immunity. High peak levels of T cells and neutralizing antibodies 15 days post-vaccination associated with protection from breakthrough infections., Conclusion: Booster vaccination in naïve individuals and the inclusion of viral antigens other than spike in future vaccine formulations could be useful strategies to prevent SARS-CoV-2 breakthrough infections., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Almendro-Vázquez, Chivite-Lacaba, Utrero-Rico, González-Cuadrado, Laguna-Goya, Moreno-Batanero, Sánchez-Paz, Luczkowiak, Labiod, Folgueira, Delgado and Paz-Artal.)
- Published
- 2022
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6. Primary Immune Regulatory Disorders With an Autoimmune Lymphoproliferative Syndrome-Like Phenotype: Immunologic Evaluation, Early Diagnosis and Management.
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López-Nevado M, González-Granado LI, Ruiz-García R, Pleguezuelo D, Cabrera-Marante O, Salmón N, Blanco-Lobo P, Domínguez-Pinilla N, Rodríguez-Pena R, Sebastián E, Cruz-Rojo J, Olbrich P, Ruiz-Contreras J, Paz-Artal E, Neth O, and Allende LM
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- Early Diagnosis, Humans, Autoimmune Lymphoproliferative Syndrome diagnosis, Autoimmune Lymphoproliferative Syndrome immunology, Autoimmune Lymphoproliferative Syndrome therapy, Primary Immunodeficiency Diseases diagnosis, Primary Immunodeficiency Diseases immunology, Primary Immunodeficiency Diseases therapy
- Abstract
Primary immune regulatory disorders (PIRD) are associated with autoimmunity, autoinflammation and/or dysregulation of lymphocyte homeostasis. Autoimmune lymphoproliferative syndrome (ALPS) is a PIRD due to an apoptotic defect in Fas-FasL pathway and characterized by benign and chronic lymphoproliferation, autoimmunity and increased risk of lymphoma. Clinical manifestations and typical laboratory biomarkers of ALPS have also been found in patients with a gene defect out of the Fas-FasL pathway (ALPS-like disorders). Following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA), we identified more than 600 patients suffering from 24 distinct genetic defects described in the literature with an autoimmune lymphoproliferative phenotype (ALPS-like syndromes) corresponding to phenocopies of primary immunodeficiency (PID) ( NRAS, KRAS ), susceptibility to EBV ( MAGT1, PRKCD, XIAP, SH2D1A, RASGRP1, TNFRSF9 ), antibody deficiency ( PIK3CD gain of function (GOF) , PIK3R1 loss of function (LOF) , CARD11 GOF), regulatory T-cells defects ( CTLA4, LRBA, STAT3 GOF , IL2RA, IL2RB, DEF6 ), combined immunodeficiencies ( ITK, STK4 ), defects in intrinsic and innate immunity and predisposition to infection ( STAT1 GOF, IL12RB1 ) and autoimmunity/autoinflammation ( ADA2, TNFAIP3,TPP2, TET2 ). CTLA4 and LRBA patients correspond around to 50% of total ALPS-like cases. However, only 100% of CTLA4, PRKCD, TET2 and NRAS/KRAS reported patients had an ALPS-like presentation, while the autoimmunity and lymphoproliferation combination resulted rare in other genetic defects. Recurrent infections, skin lesions, enteropathy and malignancy are the most common clinical manifestations. Some approaches available for the immunological study and identification of ALPS-like patients through flow cytometry and ALPS biomarkers are provided in this work. Protein expression assays for NKG2D, XIAP, SAP, CTLA4 and LRBA deficiencies and functional studies of AKT, STAT1 and STAT3 phosphorylation, are showed as useful tests. Patients suspected to suffer from one of these disorders require rapid and correct diagnosis allowing initiation of tailored specific therapeutic strategies and monitoring thereby improving the prognosis and their quality of life., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 López-Nevado, González-Granado, Ruiz-García, Pleguezuelo, Cabrera-Marante, Salmón, Blanco-Lobo, Domínguez-Pinilla, Rodríguez-Pena, Sebastián, Cruz-Rojo, Olbrich, Ruiz-Contreras, Paz-Artal, Neth and Allende.)
- Published
- 2021
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7. Next Generation Sequencing for Detecting Somatic FAS Mutations in Patients With Autoimmune Lymphoproliferative Syndrome.
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López-Nevado M, Docampo-Cordeiro J, Ramos JT, Rodríguez-Pena R, Gil-López C, Sánchez-Ramón S, Gil-Herrera J, Díaz-Madroñero MJ, Delgado-Martín MA, Morales-Pérez P, Paz-Artal E, Magerus A, Rieux-Laucat F, and Allende LM
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- Apoptosis genetics, Apoptosis immunology, Autoantibodies blood, Autoantibodies immunology, Autoimmune Lymphoproliferative Syndrome diagnosis, Autoimmunity, Biomarkers, Computational Biology methods, Gene Expression Profiling, Gene Frequency, Genetic Association Studies methods, Germinal Center, High-Throughput Nucleotide Sequencing, Humans, Immunophenotyping, Molecular Sequence Annotation, T-Lymphocytes immunology, T-Lymphocytes metabolism, fas Receptor metabolism, Autoimmune Lymphoproliferative Syndrome genetics, Autoimmune Lymphoproliferative Syndrome immunology, Genetic Predisposition to Disease, Mutation, fas Receptor genetics
- Abstract
Autoimmune lymphoproliferative syndrome (ALPS) is a primary immune regulatory disorder clinically defined by chronic and benign lymphoproliferation, autoimmunity and an increased risk of lymphoma due to a genetic defect in the FAS-FASL apoptotic pathway. Genetic defects associated with ALPS are germinal and somatic mutations in FAS gene, in addition to germinal mutations in FASLG, FADD, CASP8 and CASP10 genes. The accumulation of CD3+TCRαβ+CD4-CD8- double negative T-cells (DNT) is a hallmark of the disease and 20-25% of ALPS patients show heterozygous somatic mutations restricted to DNT in the FAS gene (ALPS-sFAS patients). Nowadays, somatic mutations in the FAS gene are detected through Sanger sequencing in isolated DNT. In this study, we report an ALPS-sFAS patient fulfilling clinical and laboratory ALPS criteria, who was diagnosed through NGS with a targeted gene panel using DNA from whole blood. Data analysis was carried out with Torrent Suite Software and variant detection was performed by both germinal and somatic variant caller plugin. The somatic variant caller correctly detected other six ALPS-sFAS patients previously diagnosed in the authors' laboratories. In summary, this approach allows the detection of both germline and somatic mutations related to ALPS by NGS, avoiding the isolation of DNT as the first step. The reads of the somatic variants could be detected even in patients with DNT in the cut off limit. Thus, custom-designed NGS panel testing may be a faster and more reliable method for the diagnosis of new ALPS patients, including those with somatic FAS mutations (ALPS-sFAS)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 López-Nevado, Docampo-Cordeiro, Ramos, Rodríguez-Pena, Gil-López, Sánchez-Ramón, Gil-Herrera, Díaz-Madroñero, Delgado-Martín, Morales-Pérez, Paz-Artal, Magerus, Rieux-Laucat and Allende.)
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- 2021
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8. Case Report: Resetting the Humoral Immune Response by Targeting Plasma Cells With Daratumumab in Anti-Phospholipid Syndrome.
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Pleguezuelo DE, Díaz-Simón R, Cabrera-Marante O, Lalueza A, Paz-Artal E, Lumbreras C, and Serrano Hernández A
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- Anticoagulants therapeutic use, Antiphospholipid Syndrome blood, Antiphospholipid Syndrome diagnosis, Antiphospholipid Syndrome immunology, Biomarkers blood, Female, Humans, Off-Label Use, Plasma Cells immunology, Plasma Cells metabolism, Recurrence, Treatment Outcome, Venous Thromboembolism blood, Venous Thromboembolism diagnosis, Venous Thromboembolism immunology, Young Adult, Antibodies, Antiphospholipid blood, Antibodies, Monoclonal therapeutic use, Antiphospholipid Syndrome drug therapy, Immunity, Humoral drug effects, Immunologic Factors therapeutic use, Plasma Cells drug effects, Venous Thromboembolism prevention & control
- Abstract
Introduction: Monoclonal antibodies (mAb) targeting plasma cells are malignant gammopathy designed and approved therapies. In recent years, these antibodies have also been increasingly introduced for non-malignant conditions such as autoimmune-mediated diseases. The Anti-Phospholipid Syndrome (APS) is an immune-mediated disorder in which autoantibodies against phospholipid associated proteins could elicit the activation of the coagulation cascade in specific situations. Therefore, the mainstream treatment for APS patients is the use of anticoagulant therapy. However, there are refractory patients who would benefit from targeting the antibodies rather than their effects. Rituximab, a B-cell depleting mAb, and intravenous immunoglobulins (IVIG) have been used in APS patients without showing a clear beneficial effect or a significant drop in anti-phospholipid antibody (aPL) levels., Clinical Case: We present our first APS case treated with daratumumab, an anti-CD38 mAb, in a 21-year-old patient with APS who presented with recurrent venous thromboembolic events despite adequate anticoagulant therapy. She tested positive for lupus anticoagulant, anti-cardiolipin IgG, anti-beta-2-glycoprotein-I IgG and anti-phosphatidylserine/prothrombin IgG and IgM. She was administered one dose weekly of daratumumab for 4 weeks. The treatment showed an adequate safety profile and was well tolerated. The patient was discharged after undergoing a clinically significant improvement. After the therapy, her levels of positive aPL declined significantly and most continued to decrease during the next three months. The patient experienced a new thrombotic episode two years after the therapy associated with poor adherence to antithrombotic therapy., Conclusions: The treatment with daratumumab showed an adequate safety profile, was well tolerated and led to a significant clinical improvement. Levels of aPL lowered on therapy and the next three months and then rose again during follow-up. Further investigation is needed to better elucidate the role and optimal timing and doses of daratumumab in treatment of refractory APS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Pleguezuelo, Díaz-Simón, Cabrera-Marante, Lalueza, Paz-Artal, Lumbreras and Serrano Hernández.)
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- 2021
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9. Tolerogenic Role of Myeloid Suppressor Cells in Organ Transplantation.
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Ochando J, Conde P, Utrero-Rico A, and Paz-Artal E
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- Allografts, Animals, Humans, Myeloid-Derived Suppressor Cells pathology, Myeloid-Derived Suppressor Cells immunology, Organ Transplantation, Transplantation Tolerance
- Abstract
Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of immature cells of myeloid origin with a specific immune inhibitory function that negatively regulates the adaptive immune response. Since MDSC participate in the promotion of tolerance in the context of organ transplantation, therapeutic strategies that regulate the induction and development of MDSC have been the center of scientist attention. Here we review literature regarding induction of MDSC with demonstrated suppressive function among different types of allografts and their mechanism of action. While manipulation of MDSC represents a potential therapeutic approach for the promotion of donor specific tolerance in solid organ transplantation, further characterization of their specific phenotype, which distinguishes MDSC from non-suppressive myeloid cells, and detailed evaluation of the inhibitory mechanism that determines their suppressive function, is necessary for the realistic application of MDSC as biomarkers in health and disease and their potential use as immune cell therapy in organ transplantation.
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- 2019
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10. Acquired and Innate Immunity Impairment and Severe Disseminated Mycobacterium genavense Infection in a Patient With a NF-κB1 Deficiency.
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Gonzalez-Granado LI, Ruiz-García R, Blas-Espada J, Moreno-Villares JM, Germán-Diaz M, López-Nevado M, Paz-Artal E, Toldos O, Rodriguez-Gil Y, de Inocencio J, Domínguez-Pinilla N, and Allende LM
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- Biopsy, Bone Marrow metabolism, Child, Cytokines metabolism, Humans, Immunophenotyping, Male, Mutation, Pedigree, Phenotype, Skin pathology, Adaptive Immunity, Immunity, Innate, Immunologic Deficiency Syndromes complications, Immunologic Deficiency Syndromes genetics, Mycobacterium immunology, Mycobacterium Infections diagnosis, Mycobacterium Infections etiology, NF-kappa B p50 Subunit deficiency
- Abstract
Background: NF-κB1 is a master regulator of both acquired and innate responses. NFKB1 loss-of-function mutations elicit a wide clinical phenotype with asymptomatic individuals at one end of the spectrum and patients with common variable immunodeficiency, combined immunodeficiency or autoinflammation at the other. Impairment of acquired and innate immunity and disseminated Mycobacterium genavense infection expands the clinical and immunological phenotype of NF-κB1 deficiency. Objective: Functional and molecular characterization of a patient with a novel phenotype of NF-κB1 deficiency. Methods: Circulating T, B, dendritic cell subsets and innate or unconventional T-cells were quantified. The cytokine production in stimulated whole blood samples was assessed and molecular characterization by next generation sequencing and gene expression assays were also performed. Results: We report a patient presenting with features of combined immunodeficiency (CID) and disseminated Mycobacterium genavense infection. Sequencing of genomic DNA identified a novel synonymous mutation (c.705G > A) in NFKB1 gene which resulted in exon 8 skipping and haploinsufficiency of the NF-κB1 subunit p50. The susceptibility to atypical mycobacterial infection has not been previously reported and may be the result of a dendritic cell deficiency. A selective deficiency of circulating follicular helper T (cTFH) cells responsible for mediating the differentiation of naive B cells into memory and plasma cells was also present in the patient. It could affect the maturation of innate or unconventional T cells where NF-κB1 could also be involved. Conclusion: These findings showed that the role of NF-κB1 in humans could be critical for the development of acquired and innate immunity and further highlights the role of human T cells in anti-mycobacterial immunity.
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- 2019
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11. Acquired Senescent T-Cell Phenotype Correlates with Clinical Severity in GATA Binding Protein 2-Deficient Patients.
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Ruiz-García R, Rodríguez-Vigil C, Marco FM, Gallego-Bustos F, Castro-Panete MJ, Diez-Alonso L, Muñoz-Ruiz C, Ruiz-Contreras J, Paz-Artal E, González-Granado LI, and Allende LM
- Abstract
GATA binding protein 2 (GATA2) deficiency is a rare disorder of hematopoiesis, lymphatics, and immunity caused by spontaneous or autosomal dominant mutations in the GATA2 gene. Clinical manifestations range from neutropenia, lymphedema, deafness, to severe viral and mycobacterial infections, bone marrow failure, and acute myeloid leukemia. Patients also present with monocytopenia, dendritic cell, B- and natural killer (NK)-cell deficiency. We studied the T-cell and NK-cell compartments of four GATA2-deficient patients to assess if changes in these lymphocyte populations could be correlated with clinical phenotype. Patients with more severe clinical complications demonstrated a senescent T-cell phenotype whereas patients with lower clinical score had undetectable changes relative to controls. In contrast, patients' NK-cells demonstrated an immature/activated phenotype that did not correlate with clinical score, suggesting an intrinsic NK-cell defect. These studies will help us to determine the contribution of T- and NK-cell dysregulation to the clinical phenotype of GATA2 patients, and may help to establish the most accurate therapeutic options for these patients. Asymptomatic patients may be taken into consideration for hematopoietic stem cell transplantation when dysregulation of T-cell and NK-cell compartment is present.
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- 2017
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