Distribution Of HLA-B Research Articles

HLA alleles, especially amino-acid signatures of HLA-DPB1, might contribute to the molecular pathogenesis of early-onset autoimmune thyroid disease.

The major histocompatibility complex region has been suggested to play an important role in the development of autoimmune thyroid disease (AITD). In this study, we investigated the associations of human leukocyte antigen (HLA) alleles and amino acid variants of HLA with early-onset AITD. HLA class I and class II genes were analyzed in 116 Korean children with AITDs (Graves’ disease [GD]: 71, Hashimoto’s disease [HD]: 45) and 142 healthy controls. HLA-B*46:01 (OR = 3.96, Pc = 0.008), -C*01:02 (OR = 2.51 Pc = 0.04), -DPB1*02:02 (OR = 3.99, Pc = 0.04), and -DPB1*05:01 (OR = 4.6, Pc = 0.003) were significantly associated with GD, and HLA-A*02:07 (OR = 4.68, Pc = 0.045) and -DPB1*02:02 (OR = 6.57, Pc = 0.0001) with HD. The frequency of HLA-DPB1*05:01 was significantly higher in GD patients than in HD patients (Pc = 0.0005). Furthermore, differences were found between patients with Thyroid associated ophthalmopathy (TAO) and those without TAO in the distribution of HLA-B*54:01 (8.6% vs. 30.6%, P = 0.04) and -C*03:03 (37.1% vs. 11.1%, P = 0.02). In the analysis of amino acid variants of HLA molecules, both Leu35 (OR = 23.38, P = 0.0002) and Glu55 (OR = 23.38, P = 0.0002) of HLA-DPB1 were strongly associated with GD and showed different distributions between GD and HD (P = 0.001). Our results suggest that HLA alleles, especially amino-acid signatures of the HLA-DP β chain, might contribute to the molecular pathogenesis of early-onset AITD.

Rapid and Reliable Genotyping ofHLA-B*57:01in Four Chinese Populations Using a Single-Tube Duplex Real-Time Polymerase Chain Reaction Assay

HLA-B*57:01 is strongly associated with severe adverse drug reaction induced by the anti-HIV drug abacavir (ABC) and antibiotic flucloxacillin. This study was dedicated to establishing a new method for HLA-B*57:01 genotyping and investigating the HLA-B*57:01 distribution pattern in four Chinese populations. A single-tube duplex real-time polymerase chain reaction (PCR) system was established by combining the amplification refractory mutation system and TaqMan probe. The reliability of this assay was validated by comparing the genotyping results with those by sequence-based typing. With this assay, the distribution of HLA-B*57:01 in 354 blood samples from four ethnic groups, namely, Han, Tibetan, Uighur, and Buyei, was determined. A 100% concordance was observed between the results of real-time PCR and sequence-based typing in 50 Uighur samples. As low as 0.016 ng DNA that carried HLA-B*57:01 could be detected with this assay. HLA-B*57:01 carriers identified in 100 Northern Han Chinese, 104 Buyeis, 100 Tibetans, and 50 Uighurs were 0, 1 (0.96%), 3 (3%), and 6 (12%), respectively. The carrier rate of HLA-B*57:01 in Uighur was significantly higher than those in Northern Han (p = .001) and Buyei (p = .005). The newly established real-time PCR assay provides a rapid and reliable tool for HLA-B*57:01 allele screening before the prescription of ABC and flucloxacillin in clinical practice.

A multiplex allele-specific real-time polymerase chain reaction assay for HLA-B*13:01 genotyping in four Chinese populations.

Human leukocyte antigen HLA-B*13:01 is identified currently as a marker of individual susceptibility to drug-induced hypersensitivity reaction, such as dapsone-induced hypersensitivity reactions (DIHRs) and trichloroethylene-induced dermatitis. Therefore, screening for the HLA-B*13:01 allele can assist clinics in identifying patients at risk of developing DIHRs. By combining the allele-specific primers with TaqMan probes, we established a single tube, triplex real-time PCR to detect HLA-B*13:01. The reliability of this assay was validated by the comparison of genotyping results with those by sequence-based typing (SBT). With this assay, the distribution of HLA-B*13:01 in a total of 350 blood samples from four ethnic groups: Han, Tibetan, Uighur, and Buyei were determined. A 100% concordance was observed between the results with the established real-time PCR and SBT in 100 samples. The detection limit of this assay was 0.016 ng genomic DNA. The prevalence of HLA-B*13:01 carriers were 11%, 8%, 1%, and 2% in the Buyei (n = 100), Northern Han (n = 100), Tibetan (n = 100), and Uighur (n = 50) populations, respectively. The multiplex real-time PCR assay provided a fast and reliable method for accurate detection of HLA-B*13:01 allele prior to dapsone administration in clinical practice and onset of the reaction after exposure to trichloroethylene.

Takayasu's arteritis is associated with HLA-B*52, but not with HLA-B*51, in Turkey

IntroductionHLA-B*51 and HLA-B*52 are two close human leukocyte antigen (HLA) allele groups with minor amino acid differences. However, they are associated with two different vasculitides (HLA-B*51 in Behçet's disease and HLA-B*52 in Takayasu's arteritis (TAK)) and with major clinical and immunological differences. In this study, we aimed to screen a large cohort of TAK patients from Turkey for the presence of HLA-B*51 and HLA-B*52 as susceptibility and severity factors.MethodsTAK patients (n = 330) followed at a total of 15 centers were included in the study. The mean age of the patients was 37.8 years, and 86% were women. DNA samples from the patients and healthy controls (HC; n = 210) were isolated, and the presence of HLA-B*51 or HLA-B*52 was screened for by using PCR with sequence-specific primers.ResultsWe found a significant association of HLA-B*52 with TAK (20.9% vs HC = 6.7%, P = 0.000, OR = 3.7, 95% CI = 2.02 to 6.77). The distribution of HLA-B*51 did not differ between TAK patients and HCs (22.7% vs 24.8%, OR = 0.9, 95% CI = 0.60 to 1.34). The presence of HLA-B*52 decreased in late-onset patients (> 40 years of age; 12.0%, P = 0.024, OR = 0.43, 95% CI = 0.20 to 0.91). Patients with angiographic type I disease with limited aortic involvement also had a lower presence of HLA-B*52 compared to those with all other disease subtypes (13.1% vs 26%, P = 0.005, OR = 0.43, 95% CI = 0.23 to 0.78).ConclusionsIn this study, the previously reported association of TAK with HLA-B*52 in other populations was confirmed in patients from Turkey. The functional relevance of HLA-B*52 in TAK pathogenesis needs to be explored further.

HLA‐B*15 subtypes distribution in Han population in Beijing, China, as compared with those of other populations

To identify HLA-B*15 subtypes distribution in Han population in Beijing, People's Republic of China, 826 unrelated healthy individuals were typed using the polymerase chain reaction-sequence-based typing method. Within the 246 HLA-B*15 positive individuals, 29 HLA-B*15 alleles were identified, the most predominant of which is B*1501 (40.07%), followed by B*1502 (12.87%), B*1511 (12.87%), B*1518 (9.19%) and B*1532 (3.31%). The distribution of HLA-B*15 subtype frequencies was compared between the Beijing Han, eight other Chinese ethnic minorities and six Chinese populations covering the mainland of China, Taiwan, Hong Kong and Singapore. A neighbor-joining phylogenetic tree was constructed and revealed that the Beijing Han population clustered into the northern populations group and had a closer relationship with northern Han and Hui than with southern Han or other ethnic minorities. These results thus provide useful information that can be used in anthropology, selection for bone marrow transplantation as well as in disease-association study, such as in carbamazepine (CBZ)-induced Stevens-Johnson syndrome and toxic epidermal necrolysis.

Distribution of HLA-B*27 subtypes in Tunisians and their association with ankylosing spondylitis

Objective The human leukocyte antigen HLA-B27 is a class I antigen of the major histocompatibility complex strongly associated with ankylosing spondylitis (AS) and other related spondyloarthropathies (SpAs). The mechanism of this association remains unknown. HLA-B27 is a serologic specificity that represents a family of at least 25 different HLA-B27 alleles (2701–2725). These alleles are closely related by nucleotide sequence homology, but differ in ethnic distribution. The purpose of the present study is to investigate the distribution of HLA-B27 alleles in healthy controls and in patients with ankylosing spondylitis (AS). Methods We selected 160 HLA-B27-positive individuals (39 controls and 121 patients with ankylosing spondylitis). Typing of HLA-B27, and Cw alleles were performed by polymerase chain reaction amplification with sequence specific primers (PCR–SSP), and by serological typing (microlymphocytotoxicity). Results Seven B27 subtypes were identified: B*2702, 03, 04, 05, 07, 09 and B*2714. The distribution of these alleles in the population of patients was B*2702 (47.1%) and B*2705 (47.1%). These subtypes were also detected in 16 (41%) and 16 (41%), respectively of the 39 control subjects. HLA-B*2707 was detected in 4 (3.31%) patients and in 3 (7.6%) controls. B*2704, 09 and B*2714 were relatively rare and were detected in one subject each. No significant differences were noticed in the frequencies and distribution of HLA-B27 alleles between patients and controls. Conclusions Our results show a restricted number of HLA B27 subtypes associated with AS. B*2702 and B*2705 were equally common in patients and controls. The most prominent B27/Cw haplotypes in the patient groups and controls were B*2702/Cw02022 and B*2705/Cw02022.