Simple Measurement of IgA Predicts Immunity and Mortality in Ataxia-Telangiectasia

Autor: Pere Soler-Palacín, Larysa Kostyuchenko, Peter Bader, Catharina Schuetz, Shereen M. Reda, Ruth Pia Duecker, Bodo Grimbacher, Sharhzad Bakhtiar, Nizar Mahlaoui, Ralf Schubert, Dagmar Graf, Juan Luis Santos Pérez, E.V. Deripapa, Necil Kutukculer, Claudio Pignata, Seraina Prader, Isabelle Meyts, Maria Kanariou, Markus G. Seidel, Sandra Woelke, Peter Ciznar, Aileen Buecker, Stephan Ehl, Koen J. van Aerde, E. Graham Davies, Carlos Rodríguez-Gallego, Sabine Huenecke, Fabian Hauck, Gerhard Kindle, Hermann Kreyenberg, John David M Edgar, Tim Niehues, Hans-Juergen Laws, Helena Donath, Kai Lehmberg, Barbara Pietrucha, Mary Slatter, Renate Krueger, Elizabeth M. McDermott, Nermeen Galal, Michiel van der Flier, Claire Bethune, Horst von Bernuth, Peter D. Arkwright, Laura Hora Marques, Ismail Reisli, Stefan Zielen, Ulrich Baumann, Luis Ignacio Gonzalez Granado, Sara Sebnem Kilic, Sabine M El-Helou, Alessandro Plebani, Svetlana O. Sharapova
Přispěvatelé: Institut Català de la Salut, [Zielen S, Duecker RP, Woelke S, Donath H, Buecker A] Division of Allergology, Pulmonology and Cystic Fibrosis, Department for Children and Adolescents, Goethe University, Frankfurt, Germany. [Bakhtiar S] Division for Stem Cell Transplantation, Immunology and Intensive Care Unit, Department for Children and Adolescents, Goethe University, Frankfurt, Germany. [Soler-Palacín P] Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Unitat de Patologia Infecciosa i Immunodeficiències de Pediatria, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain, Vall d'Hebron Barcelona Hospital Campus
Rok vydání: 2021
Předmět:
Male
Lymphocyte
lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4]
Atàxia de Friedreich - Prognosi
Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::Cerebellar Diseases::Cerebellar Ataxia::Spinocerebellar Ataxias::Ataxia Telangiectasia [DISEASES]
Ataxia-telangiectasia
Liver disease
T-Lymphocyte Subsets
Immunology and Allergy
Repertoire
Otros calificadores::Otros calificadores::/inmunología [Otros calificadores]
IgG Deficiency
Child
Immunodeficiency
B-Lymphocytes
Middle Aged
Immunoglobulina A
medicine.anatomical_structure
Phenotype
Child
Preschool

T-Cell Subsets
Cohort
Deficiency
Original Article
Female
IgA deficiency
Receptor
Adult
enfermedades del sistema nervioso::enfermedades del sistema nervioso central::enfermedades cerebrales::enfermedades cerebelosas::ataxia cerebelosa::ataxias espinocerebelosas::ataxia telangiectasia [ENFERMEDADES]
Adolescent
Immunology
Generation
Immunoglobulins
Infections
Ataxia Telangiectasia
Young Adult
Immunity
Other subheadings::Other subheadings::/immunology [Other subheadings]
Lymphopenia
medicine
Humans
Lymphocyte Count
ddc:610
Mortality
Surrogate endpoint
business.industry
Infant
medicine.disease
Immunoglobulin A
Oxidative Stress
Respiratory failure
Immunoglobulin M
Immunoglobulin G
Atm
business
Zdroj: Journal of Clinical Immunology, 41, 1878-1892
Dipòsit Digital de Documents de la UAB
Universitat Autònoma de Barcelona
Scientia
Journal of Clinical Immunology, 41, 8, pp. 1878-1892
Journal of Clinical Immunology
ISSN: 0271-9142
Popis: Patients with ataxia-telangiectasia (A-T) suffer from progressive cerebellar ataxia, immunodeficiency, respiratory failure, and cancer susceptibility. From a clinical point of view, A-T patients with IgA deficiency show more symptoms and may have a poorer prognosis. In this study, we analyzed mortality and immunity data of 659 A-T patients with regard to IgA deficiency collected from the European Society for Immunodeficiencies (ESID) registry and from 66 patients with classical A-T who attended at the Frankfurt Goethe-University between 2012 and 2018. We studied peripheral B- and T-cell subsets and T-cell repertoire of the Frankfurt cohort and survival rates of all A-T patients in the ESID registry. Patients with A-T have significant alterations in their lymphocyte phenotypes. All subsets (CD3, CD4, CD8, CD19, CD4/CD45RA, and CD8/CD45RA) were significantly diminished compared to standard values. Patients with IgA deficiency (n = 35) had significantly lower lymphocyte counts compared to A-T patients without IgA deficiency (n = 31) due to a further decrease of naive CD4 T-cells, central memory CD4 cells, and regulatory T-cells. Although both patient groups showed affected TCR-ss repertoires compared to controls, no differences could be detected between patients with and without IgA deficiency. Overall survival of patients with IgA deficiency was significantly diminished. For the first time, our data show that patients with IgA deficiency have significantly lower lymphocyte counts and subsets, which are accompanied with reduced survival, compared to A-T patients without IgA deficiency. IgA, a simple surrogate marker, is indicating the poorest prognosis for classical A-T patients. Both non-interventional clinical trials were registered at clinicaltrials.gov 2012 (Susceptibility to infections in ataxia-telangiectasia; NCT02345135) and 2017 (Susceptibility to Infections, tumor risk and liver disease in patients with ataxia-telangiectasia; NCT03357978)
Projekt DEAL; German Federal Ministry of Education and Research (BMBF) [01GM0896, 01GM1111B, 01GM1517C, 01EO1303, 01ZZ1801B]; EU [HEALTHF2-2008-201549]; Novartis; GlaxoSmithKline; LFB; UCB UK; Plasma Protein Therapeutics Association (PPTA),; Care-for-Rare Foundation; PROimmune e.V; Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) [39087428]; UK National Institute of Health Research; Great Ormond Street Hospital Biomedical Research Centre
Open Access funding enabled and organized by Projekt DEAL. The ESID Registry was supported by the German Federal Ministry of Education and Research (BMBF 01GM0896, 01GM1111B, 01GM1517C, 01EO1303 and 01ZZ1801B) EU grant no. HEALTHF2-2008-201549 (EURO-PADnet), the pharmaceutical companies Novartis, GlaxoSmithKline, LFB, and UCB UK, the Plasma Protein Therapeutics Association (PPTA), the Care-for-Rare Foundation, PROimmune e.V, LFB, and the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence StrategyEXC 2155 RESIST-Project ID 39087428. EGD is supported by the UK National Institute of Health Research and the Great Ormond Street Hospital Biomedical Research Centre.
Databáze: OpenAIRE