Format

Send to

Choose Destination
J Clin Endocrinol Metab. 2014 Jan;99(1):E177-82. doi: 10.1210/jc.2013-2852. Epub 2013 Dec 20.

HLA class II haplotypes differentiate between the adult autoimmune polyglandular syndrome types II and III.

Author information

1
Laboratory of Immunogenetics/HLA (B.K.F., C.W.), German Red Cross Blood Service West, Bad Kreuznach 55543, Germany; Molecular Thyroid Research Laboratory (N.M., G.J.K.), Johannes Gutenberg University Medical Center, Mainz 55101, Germany; Bioinformatics Unit (T.A.) and Center for Transfusion Medicine (J.B.), German Red Cross Blood Service West, Hagen 58097, Germany.

Abstract

BACKGROUND:

Genetics of the adult autoimmune polyglandular syndrome (APS) is poorly understood.

AIM:

The aim of this study was to gain further insight into the genetics of the adult APS types. SITE: The study was conducted at a university referral center.

METHODS:

The human leukocyte antigen (HLA) class II alleles, haplotypes, and genotypes were determined in a large cohort of patients with APS, autoimmune thyroid disease (AITD), and type 1 diabetes and in healthy controls by the consistent application of high-resolution typing at a four-digit level.

RESULTS:

Comparison of the allele and haplotype frequencies significantly discriminated patients with APS vs AITD and controls. The HLA class II alleles DRB1*03:01 *04:01, DQA1*03:01, *05:01, DQB1*02:01, and *03:02 were observed more frequently (P<.001) in APS than in AITD and controls, whereas the alleles DRB1*15:01, DQB1*03:01, and *06:02 were underrepresented in APS vs AITD (Pc<.001) and controls (Pc<.01), respectively. The DRB1*03:01-DQA1*05:01-DQB1*02:01 (DR3-DQ2) and DRB1*04:01-DQA1*03:01:DQB1*03:02 (DRB1*04:01-DQ8) haplotypes were overrepresented in APS (Pc<.001). Combination of both haplotypes to a genotype was highly prevalent in APS vs AITD and controls (Pc<.001). Dividing the APS collective into those with Addison's disease (APS type II) and those without Addison's disease but including type 1 diabetes and AITD (APS type III) demonstrated DR3-DQ2/DRB1*04:01-DQ8 as a susceptibility genotype in APS III (Pc<.001), whereas the DR3-DQ2/DRB1*04:04-DQ8 genotype correlated with APS II (Pc<.001). The haplotypes DRB1*11:01-DQA1*05:05-DQB1*03:01 and DRB1*15:01-DQA1*01:02-DQB1*06:02 are protective in APS III but not in type II (Pc<.01).

CONCLUSIONS:

HLA class II haplotypes differentiate between the adult APS types II and III. Susceptible haplotypes favor the development of polyglandular autoimmunity in patients with AITD.

PMID:
24187405
DOI:
10.1210/jc.2013-2852
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Silverchair Information Systems
Loading ...
Support Center