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Winkler, C. ; Jolink, M. ; Knopff, A. ; Kwarteng, N.-A. ; Achenbach, P. ; Bonifacio, E. ; Ziegler, A.-G.

Age, HLA, and sex define a marked risk of organ-specific autoimmunity in first-degree relatives of patients with type 1 diabetes.

Diabetes Care 42, 1684-1691 (2019)
Verlagsversion Postprint Forschungsdaten DOI PMC
Open Access Green
OBJECTIVE Autoimmune diseases can be diagnosed early through the detection of autoantibodies. The aim of this study was to determine the risk of organ-specific autoimmunity in individuals with a family history of type 1 diabetes. RESEARCH DESIGN AND METHODS The study cohort included 2,441 first-degree relatives of patients with type 1 diabetes who were prospectively followed from birth to a maximum of 29.4 years (median 13.2 years). All were tested regularly for the development of autoantibodies associated with type 1 diabetes (islet), celiac disease (transglutaminase), or thyroid autoimmunity (thyroid peroxidase). The outcome was defined as an autoantibody-positive status on two consecutive samples. RESULTS In total, 394 relatives developed one (n = 353) or more (n = 41) of the three disease-associated autoantibodies during follow-up. The risk by age 20 years was 8.0% (95% CI 6.8-9.2%) for islet autoantibodies, 6.3% (5.1-7.5%) for transglutaminase autoantibodies, 10.7% (8.9-12.5%) for thyroid peroxidase autoantibodies, and 21.5% (19.5-23.5%) for any of these autoantibodies. Each of the three disease-associated autoantibodies was defined by distinct HLA, sex, genetic, and age profiles. The risk of developing any of these autoantibodies was 56.5% (40.8-72.2%) in relatives with HLA DR3/DR3 and 44.4% (36.6-52.2%) in relatives with HLA DR3/DR4-DQ8. CONCLUSIONS Relatives of patients with type 1 diabetes have a very high risk of organ-specific autoimmunity. Appropriate counseling and genetic and autoantibody testing for multiple autoimmune diseases may be warranted for relatives of patients with type 1 diabetes.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Antibody Standardization Program; Islet Autoantibodies; Thyroid Autoimmunity; Celiac-disease; Beta-cell; Dq Types; Children; Childhood; Mellitus; Insulin
ISSN (print) / ISBN 0149-5992
e-ISSN 1935-5548
Zeitschrift Diabetes Care
Quellenangaben Band: 42, Heft: 9, Seiten: 1684-1691 Artikelnummer: , Supplement: ,
Verlag American Diabetes Association
Verlagsort Alexandria, Va.
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes Research Type 1 (IDF)
Institute for Pancreatic Beta Cell Research (IPI)