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Human leukocyte antigen-A24:02-B40:247-C03:04-DRB116:02, a deduced probable human leukocyte antigen haplotype associated with a low-incidence human leukocyte antigen allele B*40:247 in Taiwanese individuals: A case analysis.

ABSTRACT: HLA-B*40:247 is a low incidence allele in the HLA-B locus. The aim of this study is to confirm the ethnicity of B*40:247 and its deduced probable HLA- associated haplotype in Taiwanese individuals.A total of 2,329 unrelated Taiwanese individuals and 66,212 unrelated mainland Chinese individuals were tested for HLA using a sequence-based typing method. We confirmed the low incidence allele B*40:247 in Taiwanese. Polymerase chain reaction was performed to amplify exons 2, 3 and 4 of the HLA-A and HLA-B loci and exon 2 of the HLA-DRB1 locus using group-specific primer sets. The amplicons were sequenced in both directions with the *BigDye Terminator Cycle Sequencing Ready Reaction Kit according to the manufacturer's protocols.The DNA sequence of B*40:247 is identical to B*40:01:01 in exons 2, 3 and 4 except for residue 853, where G of B*40:01:01 is changed to A in B*40:247 (codon 261, GTA->ATA). The nucleotide replacement causes a one amino acid change at codon 261 where V (valine) of B*40:01:01 is replaced by I (isoleucine) in B*40:247. We deduced the probable HLA haplotype associated with B*40:247 in Taiwanese to be HLA-A*24:02-B*40:247-C*03:04-DRB1*16:02.Information on the ethnicity and distribution of B*40:247 and its deduced probable HLA haplotype in association with the low incidence allele is of value for HLA testing laboratories for reference purposes and can help bone marrow donor registries find compatible donors for patients with this uncommon HLA allele.

SUBMITTER: Yang KL

PROVIDER: S-EPMC5968747 | biostudies-literature | 2018 Apr-Jun

REPOSITORIES: biostudies-literature

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Human leukocyte antigen-A24:02-B40:247-C03:04-DRB116:02, a deduced probable human leukocyte antigen haplotype associated with a low-incidence human leukocyte antigen allele B*40:247 in Taiwanese individuals: A case analysis.

Yang Kuo-Liang KL Zheng Zheng-Zhong ZZ Lin Li-Yun LY

Tzu chi medical journal 20180401 2

<h4>Objective</h4>HLA-B*40:247 is a low incidence allele in the HLA-B locus. The aim of this study is to confirm the ethnicity of B*40:247 and its deduced probable HLA- associated haplotype in Taiwanese individuals.<h4>Materials and methods</h4>A total of 2,329 unrelated Taiwanese individuals and 66,212 unrelated mainland Chinese individuals were tested for HLA using a sequence-based typing method. We confirmed the low incidence allele B*40:247 in Taiwanese. Polymerase chain reaction was perform ...[more]

PMID: 29875587

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Project description:Background and objectivesTo study human leukocyte antigen (HLA) allele associations in anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis.MethodsA multiethnic cohort of 269 patients with anti-LGI1 encephalitis and 1,359 controls was included. Four-digit HLA sequencing and genome wide association single-nucleotide polymorphism typing imputation (0.99 concordance) were used for HLA typing. Significance of primary and secondary associations was tested using χ2, Fisher exact tests, or logistic regression with the control of population stratification covariates when applicable.ResultsDRB1*07:01 and DQA1*02:01, 2 alleles in strong linkage disequilibrium, were associated with the disease (90% vs 24%, OR = 27.8, p < 10e-50) across ethnicity independent of variation at DRB3 and DQB1, 2 flanking HLA loci. DRB1*07:01 homozygosity was associated with a doubling of risk (OR = 2.1, p = 0.010), suggesting causality. DRB1*07:01 negative subjects were younger (p = 0.003) and more frequently female (p = 0.015). Three patients with malignant thymomas did not carry DRB1*07:01, whereas patients with other tumors had high DRB1*07:01 frequency, suggesting that the presence of tumors other than thymomas may be coincidental and not causal. In both DRB1*07:01 heterozygous individuals and DRB1*07:01 negative subjects, DRB1*04:02 was associated with anti-LGI1 encephalitis, indicating an independent effect of this allele (OR = 6.85, p = 4.57 × 10-6 and OR = 8.93, p = 2.50 × 10-3, respectively). DRB1*04:02 was also independently associated with younger age at onset (β = -6.68, p = 9.78 × 10-3). Major histocompatibility complex peptide-binding predictions using LGI1-derived peptides revealed divergent binding propensities for DRB1*04:02 and DRB1*07:01 alleles, suggesting independent pathogenic mechanisms.DiscussionIn addition to the established primary DRB1*07:01 association in anti-LGI1 encephalitis, we observe a secondary effect of DRB1*04:02 with lower age at onset. Our study provides evidence for secondary effects within HLA locus that correlate with clinical phenotypes in anti-LGI1 encephalitis.

Project description:PurposeHuman leukocyte antigen (HLA) and immunity are related. Uveitis is also closely related to immunity. For example, the common presence of human leukocyte antigen (HLA)-DRB1*04 in the immune response is well known. The aim of this study was to investigate the relationship between visual prognosis and various HLA alleles before and after therapy in patients with unclassifiable uveitis, excluding those with Vogt-Koyanagi-Harada (VKH) disease.MethodsThis retrospective case series included 42 eyes from 22 consecutive patients with unclassifiable uveitis, excluding those with VKH disease. Visual acuity (VA), sex, refractive error, central retinal thickness (CRT), central choroidal thickness (CCT), and duration from onset to treatment were measured at initial and 6-month visits. Mean values of parameters were compared at each visit. Genotyping was performed by polymerase chain reaction amplification with sequence-specific primers.ResultsDRB1*04 showed a dominant change. No significant difference was observed in the other alleles. In DRB1*04, The mean differences in initial CCT, 6-month CCT, and 6-month VA showed statistically significant difference was found in best-corrected visual acuity (BCVA) between DRB1*04+ and DRB1*04- at the first visit. BCVA values at baseline and at the final visit were 0.13 ± 0.29 and 0.20 ± 0.36 in the DRB1*04+ and 0.00045 ± 0.20 and - 0.058 ± 0.11 in the DRB1*04- groups(p = 0.00465). Central Choroidal Thickness (CCT) values pretreatment and at the final visit after treatment were (pretreatment:361.00 ± 361.0 μm,after treatment: 286.00 ± 106.53 μm, p = 0.0174) in the DRB1*04+ group, and (pretreatment:281.3 ± 139.68 μm,after treatment:223.85 ± 99.034 μm, p = 0.0426) in the DRB1*04- group, respectively, indicating changes between baseline and the final visit. CCT was significantly greater in the DRB1*04+ group at both the initial visit and at 6 months. Multivariate analysis showed a significant difference between the presence or absence of DRB1*04 and sex.ConclusionHLA-DRB1*04 allele may affect visual prognosis and CCT in unclassifiable uveitis.

Project description:Gene-wide association and candidate gene studies indicate that the greatest effect on multiple sclerosis (MS) risk is driven by the HLA-DRB1*15:01 allele within the HLA-DR15 haplotype (HLA-DRB1*15:01-DQA1*01:02-DQB1*0602-DRB5*01:01). Nevertheless, linkage disequilibrium makes it difficult to define, without functional studies, whether the functionally relevant effect derives from DRB1*15:01 only, from its neighboring DQA1*01:02-DQB1*06:02 or DRB5*01:01 genes of HLA-DR15 haplotype, or from their combinations or epistatic interactions. Here, we analyzed the impact of the different HLA-DR15 haplotype alleles on disease susceptibility in a new "humanized" model of MS induced in HLA-transgenic (Tg) mice by human oligodendrocyte-specific protein (OSP)/claudin-11 (hOSP), one of the bona fide potential primary target antigens in MS. We show that the hOSP-associated MS-like disease is dominated by the DRB1*15:01 allele not only as the DRA1*01:01;DRB1*15:01 isotypic heterodimer but also, unexpectedly, as a functional DQA1*01:02;DRB1*15:01 mixed isotype heterodimer. The contribution of HLA-DQA1/DRB1 mixed isotype heterodimer to OSP pathogenesis was revealed in (DRB1*1501xDQB1*0602)F1 double-Tg mice immunized with hOSP(142-161) peptide, where the encephalitogenic potential of prevalent DRB1*1501/hOSP(142-161)-reactive Th1/Th17 cells is hindered due to a single amino acid difference in the OSP(142-161) region between humans and mice; this impedes binding of DRB1*1501 to the mouse OSP(142-161) epitope in the mouse CNS while exposing functional binding of mouse OSP(142-161) to DQA1*01:02;DRB1*15:01 mixed isotype heterodimer. This study, which shows for the first time a functional HLA-DQA1/DRB1 mixed isotype heterodimer and its potential association with disease susceptibility, provides a rationale for a potential effect on MS risk from DQA1*01:02 through functional DQA1*01:02;DRB1*15:01 antigen presentation. Furthermore, it highlights a potential contribution to MS risk also from interisotypic combination between products of neighboring HLA-DR15 haplotype alleles, in this case the DQA1/DRB1 combination.

Dataset Information

Human leukocyte antigen-A24:02-B40:247-C03:04-DRB116:02, a deduced probable human leukocyte antigen haplotype associated with a low-incidence human leukocyte antigen allele B*40:247 in Taiwanese individuals: A case analysis.

Publications

Human leukocyte antigen-A24:02-B40:247-C03:04-DRB116:02, a deduced probable human leukocyte antigen haplotype associated with a low-incidence human leukocyte antigen allele B*40:247 in Taiwanese individuals: A case analysis.

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Dataset Information

Human leukocyte antigen-A*24:02-B*40:247-C*03:04-DRB1*16:02, a deduced probable human leukocyte antigen haplotype associated with a low-incidence human leukocyte antigen allele B*40:247 in Taiwanese individuals: A case analysis.

Publications

Human leukocyte antigen-A*24:02-B*40:247-C*03:04-DRB1*16:02, a deduced probable human leukocyte antigen haplotype associated with a low-incidence human leukocyte antigen allele B*40:247 in Taiwanese individuals: A case analysis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Human leukocyte antigen-A24:02-B40:247-C03:04-DRB116:02, a deduced probable human leukocyte antigen haplotype associated with a low-incidence human leukocyte antigen allele B*40:247 in Taiwanese individuals: A case analysis.

Human leukocyte antigen-A24:02-B40:247-C03:04-DRB116:02, a deduced probable human leukocyte antigen haplotype associated with a low-incidence human leukocyte antigen allele B*40:247 in Taiwanese individuals: A case analysis.