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 IgG2deficiency showed decreased survival compared to patients with normal IgG (HR 9.2, 95%CI 3.2-26.5) and patients with normal IgG2levels (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.
authors.affiliation: Department of Neurology - Pediatric Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands. Electronic address: nienke.vanos@radboudumc.nl.
authors.forename: Nienke J H
authors.initials: NJH
authors.lastname: van Os
authors.affiliation: Department of Internal Medicine, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Anne F M
authors.initials: AFM
authors.lastname: Jansen
authors.affiliation: Department of Internal Medicine, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Marcel
authors.initials: M
authors.lastname: van Deuren
authors.affiliation: University of Iceland, Faculty of Medicine, and Children's Hospital Iceland, Landspitali-University Hospital, Iceland.
authors.forename: Asgeir
authors.initials: A
authors.lastname: Haraldsson
authors.affiliation: Department of Neurology - Pediatric Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Nieke T M
authors.initials: NTM
authors.lastname: van Driel
authors.affiliation: Department of Pediatrics and the Pediatric Immunology Unit, Ruth Children's Hospital, Rambam Medical Center, Rappaport Faculty of Medicine, Technion, Haifa, Israel.
authors.forename: Amos
authors.initials: A
authors.lastname: Etzioni
authors.affiliation: Department of Pediatrics - Pediatric Infectious Disease and Immunology, Radboudumc Amalia Children's Hospital, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Michiel
authors.initials: M
authors.lastname: van der Flier
authors.affiliation: Department of Neurology - Pediatric Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Charlotte A
authors.initials: CA
authors.lastname: Haaxma
authors.affiliation: Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Morio
authors.affiliation: Department of Paediatrics, Advanced Paediatric Centre, Postgraduate Institute of Medical Education & Research, Chandigarh, India.
authors.forename: Amit
authors.initials: A
authors.lastname: Rawat
authors.affiliation: Department of Pediatrics, Radboudumc Amalia Children's Hospital, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Michiel H D
authors.initials: MHD
authors.lastname: Schoenaker
authors.affiliation: Department of Pediatrics, Institute of Molecular Medicine, University of Brescia, Brescia, Italy.
authors.forename: Annarosa
authors.initials: A
authors.lastname: Soresina
authors.affiliation: School of Cancer Sciences, University of Birmingham, Birmingham, United Kingdom.
authors.forename: Alexander M R
authors.initials: AMR
authors.lastname: Taylor
authors.affiliation: Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Bart P C
authors.initials: BPC
authors.lastname: van de Warrenburg
authors.affiliation: Department of Pediatrics, Radboudumc Amalia Children's Hospital, Radboud University Medical Center, Nijmegen, The Netherlands; Department of Pediatrics - Pediatric Infectious Disease and Immunology, Radboudumc Amalia Children's Hospital, Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: Corry M R
authors.initials: CMR
authors.lastname: Weemaes
authors.affiliation: Department of Pediatrics, Radboudumc Amalia Children's Hospital, Radboud University Medical Center, Nijmegen, The Netherlands; Department for Health Evidence, Radboud Institute for Health Sciences, Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: Nel
authors.initials: N
authors.lastname: Roeleveld
authors.affiliation: Department of Neurology - Pediatric Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Michèl A A P
authors.initials: MAAP
authors.lastname: Willemsen
mesh_terms: D000293:Adolescent; D000328:Adult; D000361:Agammaglobulinemia / Q000150:complications / Q000276:immunology*; D001260:Ataxia Telangiectasia / Q000150:complications / Q000235:genetics / Q000276:immunology* / Q000401:mortality; D064007:Ataxia Telangiectasia Mutated Proteins / Q000235:genetics; D002423:Cause of Death; D002648:Child; D015331:Cohort Studies; D005260:Female; D006801:Humans; D053306:Hyper-IgM Immunodeficiency Syndrome / Q000150:complications / Q000276:immunology*; D017098:IgA Deficiency / Q000150:complications / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology*; D007153:Immunologic Deficiency Syndromes / Q000150:complications / Q000276:immunology; D008017:Life Expectancy; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009369:Neoplasms / Q000209:etiology / Q000235:genetics; D016017:Odds Ratio; D010641:Phenotype; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D015996:Survival Rate; D055815:Young Adult
chemical_list: D007074:Immunoglobulin G; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins
keywords: Ataxia telangiectasia; Hyper IGM phenotype; Primary immunodeficiency; Survival