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

Lookup NU author(s): Professor Mary Slatter

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© 2021, The Author(s).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 naïve 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)


Publication metadata

Author(s): Zielen S, Duecker RP, Woelke S, Donath H, Bakhtiar S, Buecker A, Kreyenberg H, Huenecke S, Bader P, Mahlaoui N, Ehl S, El-Helou SM, Pietrucha B, Plebani A, van der Flier M, van Aerde K, Kilic SS, Reda SM, Kostyuchenko L, McDermott E, Galal N, Pignata C, Perez JLS, Laws H-J, Niehues T, Kutukculer N, Seidel MG, Marques L, Ciznar P, Edgar JDM, Soler-Palacin P, von Bernuth H, Krueger R, Meyts I, Baumann U, Kanariou M, Grimbacher B, Hauck F, Graf D, Granado LIG, Prader S, Reisli I, Slatter M, Rodriguez-Gallego C, Arkwright PD, Bethune C, Deripapa E, Sharapova SO, Lehmberg K, Davies EG, Schuetz C, Kindle G, Schubert R

Publication type: Article

Publication status: Published

Journal: Journal of Clinical Immunology

Year: 2021

Volume: 41

Pages: 1878–1892

Print publication date: 01/11/2021

Online publication date: 03/09/2021

Acceptance date: 25/06/2021

Date deposited: 27/10/2023

ISSN (print): 0271-9142

ISSN (electronic): 1573-2592

Publisher: Springer

URL: https://doi.org/10.1007/s10875-021-01090-8

DOI: 10.1007/s10875-021-01090-8


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Funding

Funder referenceFunder name
01EO1303
01ZZ1801B
01GM0896
01GM1111B
01GM1517C
39087428
Care-for-Rare Foundation
Deutsche Forschungsgemeinschaft
EU
German Federal Ministry of Education and Research
Great Ormond Street Hospital Biomedical Research Centre
EURO-PADnet
EXC 2155 RESIST
LFB
GlaxoSmithKline
HEALTH-F2-2008–201549
National Institute of Health Research
Plasma Protein Therapeutics Association (PPTA)
PROimmune e.V
NovartisNovartis Pharma AG
UCB UK

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