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

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). © 2021. The Author(s).

Citation

Stefan Zielen, Ruth Pia Duecker, Sandra Woelke, Helena Donath, Sharhzad Bakhtiar, Aileen Buecker, Hermann Kreyenberg, Sabine Huenecke, Peter Bader, Nizar Mahlaoui, Stephan Ehl, Sabine M El-Helou, Barbara Pietrucha, Alessandro Plebani, Michiel van der Flier, Koen van Aerde, Sara S Kilic, Shereen M Reda, Larysa Kostyuchenko, Elizabeth McDermott, Nermeen Galal, Claudio Pignata, Juan Luis Santos Pérez, Hans-Juergen Laws, Tim Niehues, Necil Kutukculer, Markus G Seidel, Laura Marques, Peter Ciznar, John David M Edgar, Pere Soler-Palacín, Horst von Bernuth, Renate Krueger, Isabelle Meyts, Ulrich Baumann, Maria Kanariou, Bodo Grimbacher, Fabian Hauck, Dagmar Graf, Luis Ignacio Gonzalez Granado, Seraina Prader, Ismail Reisli, Mary Slatter, Carlos Rodríguez-Gallego, Peter D Arkwright, Claire Bethune, Elena Deripapa, Svetlana O Sharapova, Kai Lehmberg, E Graham Davies, Catharina Schuetz, Gerhard Kindle, Ralf Schubert. Simple Measurement of IgA Predicts Immunity and Mortality in Ataxia-Telangiectasia. Journal of clinical immunology. 2021 Nov;41(8):1878-1892

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PMID: 34477998

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