The association of HLA-DQB1, -DQA1 and -DPB1 alleles with anti- glomerular basement membrane (GBM) disease in Chinese patients

Huan Luo,Min Chen,Zhao Cui,Rui Yang,Xu-Jie Zhou,Peng-Cheng Xu,Ming-Hui Zhao

doi:10.1186/1471-2369-12-21

Huan Luo, Min Chen + Show 5 more

Open Access

https://doi.org/10.1186/1471-2369-12-21

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Abstract

BackgroundHuman leukocyte antigen (HLA) alleles are associated with many autoimmune diseases, including anti-glomerular basement membrane (GBM) disease. In our previous study, it was demonstrated that HLA-DRB1*1501 was strongly associated with anti-GBM disease in Chinese. However, the association of anti-GBM disease and other HLA class II genes, including HLA-DQB1, -DQA1,-DPB1 alleles, has rarely been investigated in Asian, especially Chinese patients. The present study further analyzed the association between anti-GBM disease and HLA-DQB1, -DQA1, and -DPB1 genes. Apart from this, we tried to locate the potential risk amino acid residues of anti-GBM disease.MethodsThis study included 44 Chinese patients with anti-GBM disease and 200 healthy controls. The clinical and pathological data of the patients were collected and analyzed. Typing of HLA-DQB1, -DQA1 and -DPB1 alleles were performed by bi-directional sequencing of exon 2 using the SeCoreTM Sequencing Kits.ResultsCompared with normal controls, the prevalence of HLA-DPB1*0401 was significantly lower in patients with anti-GBM disease (3/88 vs. 74/400, p = 4.4 × 10-4, pc = 0.039). Comparing with normal controls, the combination of presence of DRB1*1501 and absence of DPB1*0401 was significantly prominent among anti-GBM patients (p = 2.0 × 10-12, pc = 1.7 × 10-10).ConclusionsHLA-DPB1*0401 might be a protective allele to anti-GBM disease in Chinese patients. The combined presence of DRB1*1501 and absence of DPB1*0401 might have an even higher risk to anti-GBM disease than HLA-DRB1*1501 alone.

Highlights

Human leukocyte antigen (HLA) alleles are associated with many autoimmune diseases, including anti-glomerular basement membrane (GBM) disease
Human leukocyte antigen (HLA) alleles, located on the short arm of chromosome 6, have been well known to be associated with most autoimmune diseases [2]
In Asian populations, HLA-DRB1*1501 was considered as a risk allele for Japanese [4] and Chinese patients [5]. These data suggested that HLADRB1*1501 is a common risk allele for anti-GBM disease in various populations

Summary

Introduction

Human leukocyte antigen (HLA) alleles are associated with many autoimmune diseases, including anti-glomerular basement membrane (GBM) disease. The association of anti-GBM disease and other HLA class II genes, including HLA-DQB1, -DQA1,-DPB1 alleles, has rarely been investigated in Asian, especially Chinese patients. Anti-glomerular basement membrane (GBM) disease, defined by the presence of autoantibodies in the circulation against a3 chain non-collagen 1 domain of type IV collagen [a3(IV)NC1] [1], is a severe autoimmune disease. In Asian populations, HLA-DRB1*1501 was considered as a risk allele for Japanese [4] and Chinese patients [5] These data suggested that HLADRB1*1501 is a common risk allele for anti-GBM disease in various populations. The association of anti-GBM disease and HLA class II genes, including HLA-DRB1, -DQB1, -DQA1, and -DPB1 alleles, has rarely been investigated in Asian, especially Chinese patients [4,5]. We tried to locate the potential risk amino acid residues of anti-GBM disease

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Discussion

Conclusion