RT Journal Article
T1 Simple Measurement of IgA Predicts Immunity and Mortality in Ataxia-Telangiectasia.
A1 Zielen, Stefan
A1 Duecker, Ruth Pia
A1 Woelke, Sandra
A1 Donath, Helena
A1 Bakhtiar, Sharhzad
A1 Buecker, Aileen
A1 Kreyenberg, Hermann
A1 Huenecke, Sabine
A1 Bader, Peter
A1 Mahlaoui, Nizar
A1 Ehl, Stephan
A1 El-Helou, Sabine M
A1 Pietrucha, Barbara
A1 Plebani, Alessandro
A1 van der Flier, Michiel
A1 van Aerde, Koen
A1 Kilic, Sara S
A1 Reda, Shereen M
A1 Kostyuchenko, Larysa
A1 McDermott, Elizabeth
A1 Galal, Nermeen
A1 Pignata, Claudio
A1 Pérez, Juan Luis Santos
A1 Laws, Hans-Juergen
A1 Niehues, Tim
A1 Kutukculer, Necil
A1 Seidel, Markus G
A1 Marques, Laura
A1 Ciznar, Peter
A1 Edgar, John David M
A1 Soler-Palacín, Pere
A1 von Bernuth, Horst
A1 Krueger, Renate
A1 Meyts, Isabelle
A1 Baumann, Ulrich
A1 Kanariou, Maria
A1 Grimbacher, Bodo
A1 Hauck, Fabian
A1 Graf, Dagmar
A1 Granado, Luis Ignacio Gonzalez
A1 Prader, Seraina
A1 Reisli, Ismail
A1 Slatter, Mary
A1 Rodríguez-Gallego, Carlos
A1 Arkwright, Peter D
A1 Bethune, Claire
A1 Deripapa, Elena
A1 Sharapova, Svetlana O
A1 Lehmberg, Kai
A1 Davies, E Graham
A1 Schuetz, Catharina
A1 Kindle, Gerhard
A1 Schubert, Ralf
K1 Ataxia-telangiectasia
K1 IgA deficiency
K1 Immunodeficiency
K1 Immunoglobulins
K1 Lymphopenia
K1 Mortality
AB 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).
YR 2021
FD 2021-09-03
LK http://hdl.handle.net/10668/18493
UL http://hdl.handle.net/10668/18493
LA en
DS RISalud
RD Apr 9, 2025