학술논문

HLA‐DQ genotype and biochemical characterization of anti‐transglutaminase 2 antibodies in patients with type 1 diabetes mellitus in Taiwan.
Document Type
Article
Source
FASEB Journal. Jun2020, Vol. 34 Issue 6, p8459-8474. 16p.
Subject
Language
ISSN
0892-6638
Abstract
Human Leukocyte Antigen (HLA)‐DQ2 and HLA‐DQ8 are genetic risk factors for Type 1 Diabetes Mellitus (T1DM) and Celiac disease (CD) in Caucasians, but their association with Taiwanese Han population is unknown. We screened 532 Taiwanese T1DM patients for CD biomarkers including anti‐tissue transglutaminase (TGM2), anti‐gliadin and anti‐neoepitope antibodies (Abs), sequencing DQB1 genotypes, and characterized the TGM2 Abs. We report that 3.76% of Taiwanese patients had TGM2‐Abs and all had no CD's symptoms. In contrast to Caucasian's CD patients, DQ2/DQ8 only constituted ~4/5 of TGM2‐Abs positive patients, while the other ~1/5 patients belonged to different HLA genotypes. Either anti‐gliadin or anti‐neoepitope Abs coexisted with ~3/4 of TGM2‐Abs positive patients that were likely due to gluten‐ingestion, while the cause of TGM2‐Abs production for other ~1/4 of patients was unknown. Purified anti‐TGM2 IgA (TGA) and anti‐TGM2 IgG (TGG) could bind on endothelial cells surface, recognized native better than denatured forms of TGM2, and TGA inhibited TGM2's transamidation activity by up to 80% but TGG had no effects. Epitope mapping of all TGM2‐Abs positive sera demonstrated that TGM2‐Abs had heterogeneity in specificities. This is the first study on the differences between Taiwanese Han group and Caucasian in HLA genotypes and properties of TGM2‐Abs. [ABSTRACT FROM AUTHOR]