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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Accelerated progression to type 1 diabetes in the presence of HLA-A∗24 and-B∗18is restricted to multiple islet autoantibody-positive individuals with distinct HLA-DQ and autoantibody risk profiles
Diabetes Care, Volume 41, No. 5, Year 2018
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Description
OBJECTIVE: We investigated the effect of HLA class I risk alleles on disease progression in various phases of subclinical islet autoimmunity in first-degree relatives of patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: A registry-based group of siblings/offspring (aged 0-39 years) was monitored from single- to multiple-autoantibody positivity (n = 267) and from multiple-autoantibody positivity to clinical onset (n = 252) according to HLA-DQ, -A∗24, -B∗18, and -B∗39 status. Genetic markers were determined by PCR sequence-specific oligotyping. RESULTS: Unlike HLA-B∗18 or -B∗39, HLA-A∗24 was associated with delayed progression from single- to multiple-autoantibody positivity (P = 0.009) but not to type 1 diabetes. This occurredindependently from olderage(P<0.001)and absence of HLA-DQ2/DQ8 or -DQ8 (P < 0.001 and P = 0.003, respectively), and only in the presence of GAD autoantibodies. In contrast, HLA-A∗24 was associated with accelerated progression from multiple-autoantibody positivity to clinical onset (P = 0.006), but its effects were restricted to HLA-DQ8+relatives with IA-2 or zinctransporter8 autoantibodies (P = 0.002). HLA-B∗18, but not -B∗39, was also associated with more rapid progression, but only in HLA-DQ2 carriers with double positivity for GAD and insulin autoantibodies (P = 0.004). CONCLUSIONS: HLA-A∗24 predisposes to a delayed antigen spreading of humoral autoimmunity, whereas HLA-A∗24 and -B∗18 are associated with accelerated progression of advanced subclinical autoimmunity in distinct risk groups. The relation of these alleles to the underlying disease process requires further investigation. Their typing should be relevant for the preparation and interpretation of observational and interventional studies in asymptomatic type 1 diabetes. © 2018 by the American Diabetes Association.
Authors & Co-Authors
Balti Vounsia, Eric
Belgium, Brussels
Vrije Universiteit Brussel
Belgium, Jette
Universitair Ziekenhuis Brussel
van der Auwera, Bart J.R.
Belgium, Brussels
Vrije Universiteit Brussel
Weets, Ilse
Belgium, Brussels
Vrije Universiteit Brussel
Belgium, Jette
Universitair Ziekenhuis Brussel
Casteels, Kristina M.
Belgium, Brussels
Vrije Universiteit Brussel
Belgium, Leuven
Ku Leuven– University Hospital Leuven
Tenoutasse, Sylvie
Belgium, Brussels
Vrije Universiteit Brussel
Belgium, Brussels
Hospital Universitaire Des Enfants Reine Fabiola
Keymeulen, Bart
Belgium, Brussels
Vrije Universiteit Brussel
Belgium, Jette
Universitair Ziekenhuis Brussel
Pipeleers, Daniël G.
Belgium, Brussels
Vrije Universiteit Brussel
Gorus, Frans K.
Belgium, Brussels
Vrije Universiteit Brussel
Belgium, Jette
Universitair Ziekenhuis Brussel
Statistics
Citations: 14
Authors: 8
Affiliations: 5
Identifiers
Doi:
10.2337/dc17-2462
ISSN:
01495992
Research Areas
Genetics And Genomics
Noncommunicable Diseases