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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 (<jats:italic>n<\/jats:italic>\u2009=\u200935) had significantly lower lymphocyte counts compared to A-T patients without IgA deficiency (<jats:italic>n<\/jats:italic>\u2009=\u200931) due to a further decrease of na\u00efve CD4 T-cells, central memory CD4 cells, and regulatory T-cells. Although both patient groups showed affected TCR-\u00df 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)<\/jats:p>","DOI":"10.1007\/s10875-021-01090-8","type":"journal-article","created":{"date-parts":[[2021,9,4]],"date-time":"2021-09-04T00:04:45Z","timestamp":1630713885000},"page":"1878-1892","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Simple Measurement of IgA Predicts Immunity and Mortality in Ataxia-Telangiectasia"],"prefix":"10.1007","volume":"41","author":[{"given":"Stefan","family":"Zielen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth 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The study was approved by the responsible ethics committees in Frankfurt (Date May 22, 2012\/No. 121\/12, Date Nov 21, 2016, No. 504\/15).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics Approval"}},{"value":"Informed consent was obtained from all individual participants included in the study.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to Participate"}},{"value":"Written informed consent for publication of their clinical details and was obtained from the patient\/parent\/guardian\/relative of the patient. A copy of the consent form is available for review by the Editor of this journal.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for Publication"}},{"value":"The authors have the following conflicts to declare:Dr. Zielen reports honoraria from CSL-Behring, AstraZeneca; Sanofi-Aventis GmbH; Boehringer Ingelheim; Stallergenes Greer; Allergy Therapeutics, bene-Arzneimittel GmbH; Vifor Pharma GmbH; Novartis AG; GlaxoSmithKline GmbH; ALK-Abell\u00f3 Arzneimittel GmbH; Lofarma GmbH, IMS Health GmbH & Co; and Biotest Pharma GmbH, outside the submitted work.Dr. Ehl reports grants from UCB, during the conduct of the study.Dr. Sabine M. El-Helou was funded by the Federal Ministry of Education and Research (BMBF), by the European Society for Immunodeficiencies (ESID), by the Care-for-Rare Foundation, by PROimmun e.V., and by a restricted grant from LFB, CSL Behring, and Grifols. For GAIN and RESIST, she was funded by the BMBF.Dr. Kindle reports grants from ESID (European Society for Immunodeficiencies) and grants from BMBF (German Federal Ministry of Education and Research), during the conduct of the study.Dr. van Aerde reports grants from Baxter, during the conduct of the study.Dr. Laws reports personal fees from Shire; Roche; Novonordisk; Pfizer; Csl Behring, outside the submitted work.Dr. Niehues reports honoraria from uptodate.com; travelling costs from PENTA and JIR cohorts (Padua, Italy; Lausanne Switzerland), up to 2017 from PPTA (plasma protein therapeutics association).Dr. Seidel reports personal fees from Shire [Hypogammaglobulinemia (Subcutaneous IgG, hyaluronic acid, immune globulin (human))], outside the submitted work.Dr. Meyts reports grants from CSL Behring, outside the submitted work.\u00a0IM is a senior clinical investigator at FWO Vlaanderen (supported by CSL Behring Chair of Primary Immunodeficiencies, by a KU Leuven C1 Grant C16\/18\/007, by a VIB GC PID Grant, by a FWO Grants G0C8517N; and G0E8420N and by the Jeffrey Modell Foundation. IM is a recipient of a ERC-StG MORE2ADA2. This work is supported by ERN-RITA.Dr. Grimbacher reports grants from DZIF, DFG, BMBF, Fritz Thyssen Stiftung, Shire\/Baxalta, Merck, BMS, Novartis, CSL Behring, personal fees from Janssen Cilag, Novartis, during the conduct of the study, outside the submitted work.Dr. Schubert reports grants from A-T Children\u2019s Project, DFG, SPARKS\u2013Action for A-T, Starke Lunge Foundation, personal fees from Biotest Pharma GmbH and Vifor Pharma Deutschland GmbH, outside the submitted work.The other 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.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of Interest"}}]}}