HLA-DRB1 Haplotype Frequencies Research Articles

Amino acid polymorphisms in human histocompatibility leukocyte antigen class II and proinsulin epitope have impacts on type 1 diabetes mellitus induced by immune-checkpoint inhibitors.

Immune-checkpoint inhibitors are effective in various advanced cancers. Type 1 diabetes mellitus induced by them (ICI-T1DM) is a serious complication requiring prompt insulin treatment, but the immunological mechanism behind it is unclear. We examined amino acid polymorphisms in human histocompatibility leukocyte antigen (HLA) molecules and investigated proinsulin epitope binding affinities to HLA molecules. Twelve patients with ICI-T1DM and 35 patients in a control group without ICI-T1DM were enrolled in the study. Allele and haplotype frequencies of HLA-DRB1*04:05, DQB1*04:01, and most importantly DPB1*05:01 were significantly increased in patients with ICI-T1DM. In addition, novel amino acid polymorphisms in HLA-DR (4 polymorphisms), in DQ (12 polymorphisms), and in DP molecules (9 polymorphisms) were identified. These amino acid polymorphisms might be associated with the development of ICI-T1DM. Moreover, novel human proinsulin epitope clusters in insulin A and B chains were discovered in silico and in vitro peptide binding assays to HLA-DP5. In conclusion, significant amino acid polymorphisms in HLA-class II molecules, and conformational alterations in the peptide-binding groove of the HLA-DP molecules were considered likely to influence the immunogenicity of proinsulin epitopes in ICI-T1DM. These amino acid polymorphisms and HLA-DP5 may be predictive genetic factors for ICI-T1DM.

Human leucocyte antigen alleles confer susceptibility and progression to Graves’ ophthalmopathy in a Southern Chinese population

PurposeTo evaluate the contributions of human leucocyte antigen (HLA) class I and II genes in the development of Graves’ ophthalmopathy (GO) in a Southern Chinese population.MethodsEight HLA loci were genotyped...

HLA-DRB1, DQA1 and DQB1 diversity in a mixed population of paraná, Southern Brazil

Aim The purpose of this study was to determine the allelic and haplotype frequencies of HLA-DRB1, -DQA1 and -DQB1 in a mixed population from Parana, Brazil. Methods Samples of 733 donors registered in the National Registry of Bone Marrow Donors (REDOME) from the northern/northwestern Parana, Southern Brazil were analyzed. Genotyping of HLA-DRB1 was performed by PCR-SSOP HD (High Definition) with Luminex method (One Lambda®, CA, USA), and of HLA-DQA1 and DQB1 by PCR-SSO (One Lambda ®, CA, USA) medium/high resolution. To resolve ambiguities in HLA-DRB1 and -DQB1, PCR-SSP (One Lambda ®, CA, USA) was used. Allele and haplotype frequencies, Hardy-Weinberg equilibrium (HWE) and linkage disequilibrium (LD) among different loci were determined by software version 3.11 ARLEQUIN. Results The analysis of the total sample 53, 14 and 23 alleles HLA-DRB1, -DQA1 and DQB1 were identified, respectively. For HLA-DRB1 locus, the most frequent were HLA-DRB1∗07:01 (13.16%), ∗03:01 (8.86%), ∗11:01 (8.59%), ∗15:01 (6.07%), ∗13:01 (5.93%) and ∗01:01 (5.86%). For the loci HLA-DQA1 and HLA-DQB1, alleles with the following frequencies were found: HLA-DQA1∗01:02 (16.85%), ∗05:05 (16.10%), ∗01:01 (14.80%), ∗02:01 (13.16%), ∗05:01 (10.77%) and ∗03:01 (10.64%); HLA-DQB1∗03:01 (20.19%), ∗05:01 (13.98%), ∗02:02 (11.93%), ∗03:02 and ∗02:01 (9.55%) and ∗06:01 (8.59%). One hundred seventy-three HLA-DQA1/DQB1 possible haplotypes, with HLA-DQA1∗05:05/DQB1∗03:01 (15.11%), DQA1∗01:01/DQB1∗05:01 (12.89%) and DQA1∗02:01/DQB∗02:02 (11.05%) were the most frequent. We observed 1275 HLA-DRB1/DQA1/DQB1 possible haplotypes and the most common were HLA-DRB1∗07:01/DQA1∗02:01/DQB1∗02:02 (10.30%), DRB1∗03:01/DQA1∗05:01/DQB1∗02:01 (8.39%) and DRB1∗11:01/DQA1∗05:05/DQB1∗03:01 (5.91%). The distribution of HLA alleles was in HWE. For LD analysis, the strength of the associations between the pair wises HLA DRB1-DQA1, DRB1-DQB1, and DQA1-DQB1 was observed, and all of them were statistically significant (P 0.05). The HLA diversity measured by the estimated heterozygosity was very high, 0.948-0.945 for HLA-DRB1, 0.806-0.876 for HLA-DQA1 and 0.888-0.890 for HLA-DQB1. Conclusion The results obtained in this study underscore the importance of using HLA genes as a tool of research of the ethnic composition of populations.

High-resolution HLA-A, HLA-B, and HLA-DRB1 haplotype frequencies from the French Bone Marrow Donor Registry

We have estimated human leukocyte antigen (HLA) haplotype frequencies using the maximum likelihood mode, which accommodates typing ambiguities. The results of the frequency distribution of the 7015 haplotypes obtained are presented here. These include a total of 114 HLA-A, 185 HLA-B, and 76 HLA-DRB1 unique alleles at each locus. Across all populations, although the most common individual HLA alleles were HLA-A∗02:01 (29.0%), HLA-B∗07:02 (11.4%), and HLA-DRB1∗07:01 (15.9%), the most frequent haplotype was found to be HLA-A∗01:01∼B∗08:01∼DRB1∗03:01.

HLA-A, HLA-B and HLA-DRB1 haplotype frequencies in Piauí’s volunteer bone marrow donors enrolled at the Brazilian registry

This study aimed to report the antigen and haplotype frequencies (HFs) of volunteer bone marrow donors (VBMDs) from the state of Piauí who were enrolled in the National Volunteer Bone Marrow Donor Registry (REDOME). The research subjects were 21,943 volunteer bone marrow donors, predominantly young adult women (53.3%). The most frequent allelic group was HLA-A2, followed by -DRB1*13, -DRB1*04, -DRB1*07, -B*15, -B∗35, -B*44, -A*24 and -A*03.Of the 2,704 haplotypes observed, the three most frequent haplotypes were A*29 B*44 DRB1*07 (1.45%), A*01 B*08 DRB1*03 (1.4%) and A*03 B*07 DRB1*15 (0.92%). These three haplotypes were in linkage disequilibrium.PCA showed that 98% of the VBMDs have HLA allele frequencies that are very similar to those from Teresina, the capital city of Piauí. According to the PCA results, these municipalities are distributed with a close proximity to Teresina, which in turn has a close genetic proximity to the Hispanic ethnicity, intermediate proximity to Caucasians and Africans and a distant kinship to Amerindians. The hierarchical proximity of the population of Piauí to the Portuguese and Hispanic populations to shows the strong influence of the latter on the former.

Susceptibility Alleles and Haplotypes of Human Leukocyte Antigen DRB1, DQA1, and DQB1 in Autoimmune Polyglandular Syndrome Type III in Japanese Population

Background: It has been reported that HLA class II haplotypes DRB1*0405-DQA1*0303-DQB1*0401 and DRB1*0901-DQA1*0302-DQB1*0303 are major susceptibility haplotypes for type 1 diabetes mellitus (DM) in Japanese population. However, little has been reported on the susceptibility HLA class II haplotypes in Japanese patients with autoimmune polyglandular syndrome type II and type III (APS III). Patients and Methods: HLA class II haplotypes of DRB1-DQA1-DQB1 in 31 patients with APS III, 14 patients with Hashimoto’s thyroiditis alone, and 15 patients with Graves’ disease alone were examined in Japanese population. APS III patients were divided into three groups (A, B, and C) depending on the combination of autoimmune endocrine diseases. Results: In 13 APS III patients with both Hashimoto’s thyroiditis and type 1 DM (group A), the haplotype frequencies of the HLA DRB1*0802-DQA1*0401-DQB1*0402 and DRB1*0901-DQA1*0302-DQB1*0303 were significantly higher than in the controls. In patients with Hashimoto’s thyroiditis alone, the haplotype frequency of DRB1*0901-DQA1*0302-DQB1*0303 was significantly higher than in controls, whereas the frequency of DRB1*0802-DQA1*0401-DQB1*0402 did not differ significantly from those in the controls. In 11 APS III patients with both Graves’ disease and type 1 DM (group B), the haplotype frequencies of HLA DRB1*0405-DQA1*0303-DQB1*0401 and DRB1*0802-DQA1*0301-DQB1*0302 were significantly higher than in controls. In patients with Graves’ disease alone, the haplotype frequency of DRB1*0803-DQA1*0103-DQB1*0601 were significantly higher than those in controls, suggesting that the susceptibility haplotypes for group B APS III differed from those for Graves’ disease alone. In 7 APS III patients with both autoimmune thyroid diseases and pituitary disorders (group C), the haplotype frequency of HLA DRB1*0405-DQA1*0303-DQB1*0401 was significantly higher than in controls. Conclusions: Susceptible HLA class II haplotypes of DRB1-DQA1-DQB1 for APS III differ between the Japanese and Caucasian populations. More interestingly, the susceptible HLA class II haplotypes differ among the three types of Japanese APS III and are not merely a combination of susceptibility haplotypes of each endocrine disease.