Ataxia-telangiectasia:: Immunodeficiency and survival

Nienke J.h. Van Os; Anne F.m. Jansen; Marcel Van Deuren; Asgeir Haraldsson; Nieke T.m. Van Driel; Amos Etzioni; Michiel Van Der Flier; Charlotte A. Haaxma; Tomohiro Morio; Amit Rawat; Michiel H.d. Schoenaker; Annarosa Soresina; Alexander M. R. Taylor; Bart P.c. Van De Warrenburg; Corry M.r. Weemaes; Nel Roeleveld; Michèl A.a.p. Willemsen

doi:10.1016/j.clim.2017.01.009

Ataxia-telangiectasia: Immunodeficiency and survival

Nienke J.h. Van Os, Anne F.m. Jansen, Marcel Van Deuren, Asgeir Haraldsson, Nieke T.m. Van Driel, Amos Etzioni, Michiel Van Der Flier, Charlotte A. Haaxma, Tomohiro Morio, Amit Rawat, Michiel H.d. Schoenaker, Annarosa Soresina, Alexander M. R. Taylor, Bart P.c. Van De Warrenburg, Corry M.r. Weemaes, Nel Roeleveld, Michèl A.a.p. Willemsen

Cancer and Genomic Sciences

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Abstract

Ataxia-telangiectasia (AT) is a neurodegenerative disorder characterized by ataxia, telangiectasia, and immunodeficiency. An increased risk of malignancies and respiratory diseases dramatically reduce life expectancy. To better counsel families, develop individual follow-up programs, and select patients for therapeutic trials, more knowledge is needed on factors influencing survival. This retrospective cohort study of 61 AT patients shows that classical AT patients had a shorter survival than variant patients (HR 5.9, 95%CI 2.0–17.7), especially once a malignancy was diagnosed (HR 2.5, 95%CI 1.1–5.5, compared to classical AT patients without malignancy). Patients with the hyper IgM phenotype with hypogammaglobulinemia (AT-HIGM) and patients with an IgG2 deficiency showed decreased survival compared to patients with normal IgG (HR 9.2, 95%CI 3.2–26.5) and patients with normal IgG2 levels (HR 7.8, 95%CI 1.7–36.2), respectively. If high risk treatment trials will become available for AT, those patients with factors indicating the poorest prognosis might be considered for inclusion first.

Abbreviations: 95% CI, 95% confidence interval; AT, Ataxia-telangiectasia; ATM, Ataxia telangiectasia mutated; AT-HIGM, Hyper IgM phenotype with hypogammaglobulinemia; HR, Hazard ratio; OR, Odds ratio

Original language	English
Journal	Clinical Immunology
DOIs	https://doi.org/10.1016/j.clim.2017.01.009
Publication status	Published - 24 Jan 2017

Keywords

Ataxia telangiectasia
Survival
Hyper IGM phenotype
Primary immunodeficiency

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Cite this

Van Os, N. J. H., Jansen, A. F. M., Van Deuren, M., Haraldsson, A., Van Driel, N. T. M., Etzioni, A., Van Der Flier, M., Haaxma, C. A., Morio, T., Rawat, A., Schoenaker, M. H. D., Soresina, A., Taylor, A. M. R., Van De Warrenburg, B. P. C., Weemaes, C. M. R., Roeleveld, N., & Willemsen, M. A. A. P. (2017). Ataxia-telangiectasia: Immunodeficiency and survival. Clinical Immunology. https://doi.org/10.1016/j.clim.2017.01.009

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title = "Ataxia-telangiectasia:: Immunodeficiency and survival",

abstract = "Ataxia-telangiectasia (AT) is a neurodegenerative disorder characterized by ataxia, telangiectasia, and immunodeficiency. An increased risk of malignancies and respiratory diseases dramatically reduce life expectancy. To better counsel families, develop individual follow-up programs, and select patients for therapeutic trials, more knowledge is needed on factors influencing survival. This retrospective cohort study of 61 AT patients shows that classical AT patients had a shorter survival than variant patients (HR 5.9, 95%CI 2.0–17.7), especially once a malignancy was diagnosed (HR 2.5, 95%CI 1.1–5.5, compared to classical AT patients without malignancy). Patients with the hyper IgM phenotype with hypogammaglobulinemia (AT-HIGM) and patients with an IgG2 deficiency showed decreased survival compared to patients with normal IgG (HR 9.2, 95%CI 3.2–26.5) and patients with normal IgG2 levels (HR 7.8, 95%CI 1.7–36.2), respectively. If high risk treatment trials will become available for AT, those patients with factors indicating the poorest prognosis might be considered for inclusion first.Abbreviations: 95% CI, 95% confidence interval; AT, Ataxia-telangiectasia; ATM, Ataxia telangiectasia mutated; AT-HIGM, Hyper IgM phenotype with hypogammaglobulinemia; HR, Hazard ratio; OR, Odds ratio",

keywords = "Ataxia telangiectasia , Survival , Hyper IGM phenotype , Primary immunodeficiency",

author = "{Van Os}, {Nienke J.h.} and Jansen, {Anne F.m.} and {Van Deuren}, Marcel and Asgeir Haraldsson and {Van Driel}, {Nieke T.m.} and Amos Etzioni and {Van Der Flier}, Michiel and Haaxma, {Charlotte A.} and Tomohiro Morio and Amit Rawat and Schoenaker, {Michiel H.d.} and Annarosa Soresina and Taylor, {Alexander M. R.} and {Van De Warrenburg}, {Bart P.c.} and Weemaes, {Corry M.r.} and Nel Roeleveld and Willemsen, {Mich{\`e}l A.a.p.}",

year = "2017",

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Van Os, NJH, Jansen, AFM, Van Deuren, M, Haraldsson, A, Van Driel, NTM, Etzioni, A, Van Der Flier, M, Haaxma, CA, Morio, T, Rawat, A, Schoenaker, MHD, Soresina, A, Taylor, AMR, Van De Warrenburg, BPC, Weemaes, CMR, Roeleveld, N & Willemsen, MAAP 2017, 'Ataxia-telangiectasia: Immunodeficiency and survival', Clinical Immunology. https://doi.org/10.1016/j.clim.2017.01.009

TY - JOUR

T1 - Ataxia-telangiectasia:

T2 - Immunodeficiency and survival

AU - Van Os, Nienke J.h.

AU - Jansen, Anne F.m.

AU - Van Deuren, Marcel

AU - Haraldsson, Asgeir

AU - Van Driel, Nieke T.m.

AU - Etzioni, Amos

AU - Van Der Flier, Michiel

AU - Haaxma, Charlotte A.

AU - Morio, Tomohiro

AU - Rawat, Amit

AU - Schoenaker, Michiel H.d.

AU - Soresina, Annarosa

AU - Taylor, Alexander M. R.

AU - Van De Warrenburg, Bart P.c.

AU - Weemaes, Corry M.r.

AU - Roeleveld, Nel

AU - Willemsen, Michèl A.a.p.

PY - 2017/1/24

Y1 - 2017/1/24

N2 - Ataxia-telangiectasia (AT) is a neurodegenerative disorder characterized by ataxia, telangiectasia, and immunodeficiency. An increased risk of malignancies and respiratory diseases dramatically reduce life expectancy. To better counsel families, develop individual follow-up programs, and select patients for therapeutic trials, more knowledge is needed on factors influencing survival. This retrospective cohort study of 61 AT patients shows that classical AT patients had a shorter survival than variant patients (HR 5.9, 95%CI 2.0–17.7), especially once a malignancy was diagnosed (HR 2.5, 95%CI 1.1–5.5, compared to classical AT patients without malignancy). Patients with the hyper IgM phenotype with hypogammaglobulinemia (AT-HIGM) and patients with an IgG2 deficiency showed decreased survival compared to patients with normal IgG (HR 9.2, 95%CI 3.2–26.5) and patients with normal IgG2 levels (HR 7.8, 95%CI 1.7–36.2), respectively. If high risk treatment trials will become available for AT, those patients with factors indicating the poorest prognosis might be considered for inclusion first.Abbreviations: 95% CI, 95% confidence interval; AT, Ataxia-telangiectasia; ATM, Ataxia telangiectasia mutated; AT-HIGM, Hyper IgM phenotype with hypogammaglobulinemia; HR, Hazard ratio; OR, Odds ratio

AB - Ataxia-telangiectasia (AT) is a neurodegenerative disorder characterized by ataxia, telangiectasia, and immunodeficiency. An increased risk of malignancies and respiratory diseases dramatically reduce life expectancy. To better counsel families, develop individual follow-up programs, and select patients for therapeutic trials, more knowledge is needed on factors influencing survival. This retrospective cohort study of 61 AT patients shows that classical AT patients had a shorter survival than variant patients (HR 5.9, 95%CI 2.0–17.7), especially once a malignancy was diagnosed (HR 2.5, 95%CI 1.1–5.5, compared to classical AT patients without malignancy). Patients with the hyper IgM phenotype with hypogammaglobulinemia (AT-HIGM) and patients with an IgG2 deficiency showed decreased survival compared to patients with normal IgG (HR 9.2, 95%CI 3.2–26.5) and patients with normal IgG2 levels (HR 7.8, 95%CI 1.7–36.2), respectively. If high risk treatment trials will become available for AT, those patients with factors indicating the poorest prognosis might be considered for inclusion first.Abbreviations: 95% CI, 95% confidence interval; AT, Ataxia-telangiectasia; ATM, Ataxia telangiectasia mutated; AT-HIGM, Hyper IgM phenotype with hypogammaglobulinemia; HR, Hazard ratio; OR, Odds ratio

KW - Ataxia telangiectasia

KW - Survival

KW - Hyper IGM phenotype

KW - Primary immunodeficiency

U2 - 10.1016/j.clim.2017.01.009

DO - 10.1016/j.clim.2017.01.009

M3 - Article

SN - 1521-6616

JO - Clinical Immunology

JF - Clinical Immunology

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