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

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

In: J CLIN IMMUNOL, Vol. 41, No. 8, 11.2021, p. 1878-1892.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

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, Pérez, JLS, Laws, H-J, Niehues, T, Kutukculer, N, Seidel, MG, Marques, L, Ciznar, P, Edgar, JDM, Soler-Palacín, 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, Rodríguez-Gallego, C, Arkwright, PD, Bethune, C, Deripapa, E, Sharapova, SO, Lehmberg, K, Davies, EG, Schuetz, C, Kindle, G & Schubert, R 2021, 'Simple Measurement of IgA Predicts Immunity and Mortality in Ataxia-Telangiectasia', J CLIN IMMUNOL, vol. 41, no. 8, pp. 1878-1892. https://doi.org/10.1007/s10875-021-01090-8

APA

Zielen, S., Duecker, R. P., Woelke, S., Donath, H., Bakhtiar, S., Buecker, A., Kreyenberg, H., Huenecke, S., Bader, P., Mahlaoui, N., Ehl, S., El-Helou, S. M., Pietrucha, B., Plebani, A., van der Flier, M., van Aerde, K., Kilic, S. S., Reda, S. M., Kostyuchenko, L., ... Schubert, R. (2021). Simple Measurement of IgA Predicts Immunity and Mortality in Ataxia-Telangiectasia. J CLIN IMMUNOL, 41(8), 1878-1892. https://doi.org/10.1007/s10875-021-01090-8

Vancouver

Zielen S, Duecker RP, Woelke S, Donath H, Bakhtiar S, Buecker A et al. Simple Measurement of IgA Predicts Immunity and Mortality in Ataxia-Telangiectasia. J CLIN IMMUNOL. 2021 Nov;41(8):1878-1892. https://doi.org/10.1007/s10875-021-01090-8

Bibtex

@article{5986abb9a3ae4a8a89018d230db0f885,
title = "Simple Measurement of IgA Predicts Immunity and Mortality in Ataxia-Telangiectasia",
abstract = "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 na{\"i}ve 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).",
keywords = "Adolescent, Adult, Ataxia Telangiectasia/immunology, B-Lymphocytes/immunology, Child, Child, Preschool, Female, Humans, IgA Deficiency/immunology, IgG Deficiency/immunology, Immunoglobulin A/blood, Immunoglobulin G/blood, Immunoglobulin M/blood, Infant, Lymphocyte Count, Male, Middle Aged, T-Lymphocyte Subsets/immunology, Young Adult",
author = "Stefan Zielen and Duecker, {Ruth Pia} and Sandra Woelke and Helena Donath and Sharhzad Bakhtiar and Aileen Buecker and Hermann Kreyenberg and Sabine Huenecke and Peter Bader and Nizar Mahlaoui and Stephan Ehl and El-Helou, {Sabine M} and Barbara Pietrucha and Alessandro Plebani and {van der Flier}, Michiel and {van Aerde}, Koen and Kilic, {Sara S} and Reda, {Shereen M} and Larysa Kostyuchenko and Elizabeth McDermott and Nermeen Galal and Claudio Pignata and P{\'e}rez, {Juan Luis Santos} and Hans-Juergen Laws and Tim Niehues and Necil Kutukculer and Seidel, {Markus G} and Laura Marques and Peter Ciznar and Edgar, {John David M} and Pere Soler-Palac{\'i}n and {von Bernuth}, Horst and Renate Krueger and Isabelle Meyts and Ulrich Baumann and Maria Kanariou and Bodo Grimbacher and Fabian Hauck and Dagmar Graf and Granado, {Luis Ignacio Gonzalez} and Seraina Prader and Ismail Reisli and Mary Slatter and Carlos Rodr{\'i}guez-Gallego and Arkwright, {Peter D} and Claire Bethune and Elena Deripapa and Sharapova, {Svetlana O} and Kai Lehmberg and Davies, {E Graham} and Catharina Schuetz and Gerhard Kindle and Ralf Schubert",
note = "{\textcopyright} 2021. The Author(s).",
year = "2021",
month = nov,
doi = "10.1007/s10875-021-01090-8",
language = "English",
volume = "41",
pages = "1878--1892",
journal = "J CLIN IMMUNOL",
issn = "0271-9142",
publisher = "Springer New York",
number = "8",

}

RIS

TY - JOUR

T1 - Simple Measurement of IgA Predicts Immunity and Mortality in Ataxia-Telangiectasia

AU - Zielen, Stefan

AU - Duecker, Ruth Pia

AU - Woelke, Sandra

AU - Donath, Helena

AU - Bakhtiar, Sharhzad

AU - Buecker, Aileen

AU - Kreyenberg, Hermann

AU - Huenecke, Sabine

AU - Bader, Peter

AU - Mahlaoui, Nizar

AU - Ehl, Stephan

AU - El-Helou, Sabine M

AU - Pietrucha, Barbara

AU - Plebani, Alessandro

AU - van der Flier, Michiel

AU - van Aerde, Koen

AU - Kilic, Sara S

AU - Reda, Shereen M

AU - Kostyuchenko, Larysa

AU - McDermott, Elizabeth

AU - Galal, Nermeen

AU - Pignata, Claudio

AU - Pérez, Juan Luis Santos

AU - Laws, Hans-Juergen

AU - Niehues, Tim

AU - Kutukculer, Necil

AU - Seidel, Markus G

AU - Marques, Laura

AU - Ciznar, Peter

AU - Edgar, John David M

AU - Soler-Palacín, Pere

AU - von Bernuth, Horst

AU - Krueger, Renate

AU - Meyts, Isabelle

AU - Baumann, Ulrich

AU - Kanariou, Maria

AU - Grimbacher, Bodo

AU - Hauck, Fabian

AU - Graf, Dagmar

AU - Granado, Luis Ignacio Gonzalez

AU - Prader, Seraina

AU - Reisli, Ismail

AU - Slatter, Mary

AU - Rodríguez-Gallego, Carlos

AU - Arkwright, Peter D

AU - Bethune, Claire

AU - Deripapa, Elena

AU - Sharapova, Svetlana O

AU - Lehmberg, Kai

AU - Davies, E Graham

AU - Schuetz, Catharina

AU - Kindle, Gerhard

AU - Schubert, Ralf

N1 - © 2021. The Author(s).

PY - 2021/11

Y1 - 2021/11

N2 - 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).

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).

KW - Adolescent

KW - Adult

KW - Ataxia Telangiectasia/immunology

KW - B-Lymphocytes/immunology

KW - Child

KW - Child, Preschool

KW - Female

KW - Humans

KW - IgA Deficiency/immunology

KW - IgG Deficiency/immunology

KW - Immunoglobulin A/blood

KW - Immunoglobulin G/blood

KW - Immunoglobulin M/blood

KW - Infant

KW - Lymphocyte Count

KW - Male

KW - Middle Aged

KW - T-Lymphocyte Subsets/immunology

KW - Young Adult

U2 - 10.1007/s10875-021-01090-8

DO - 10.1007/s10875-021-01090-8

M3 - SCORING: Journal article

C2 - 34477998

VL - 41

SP - 1878

EP - 1892

JO - J CLIN IMMUNOL

JF - J CLIN IMMUNOL

SN - 0271-9142

IS - 8

ER -