HLA-DQB1 Alleles Research Articles

Two novel HLA-DQB1 alleles identified in potential hematopoietic stem cell donors: DQB1*03:01:50 and -DQB1*03:453.

HLA-DQB1*03:01:50 and -DQB1*03:453, two novel alleles detected by next generation sequencing.

The detection of three novel HLA-DQB1 alleles: HLA-DQB1*02:186, -DQB1*06:02:49 and -DQB1*06:391.

Three novel HLA-DQB1 alleles HLA-DQB1*02:186, -DQB1*06:02:49, and -DQB1*06:391 alleles detected during routine next generation sequencing.

The novel HLA-DQB1 allele, DQB1*06:443.

HLA-DQB1*06:443 differs from HLA-DQB1*06:03:01:01 by a change in nucleotide 287.

Frequency and distribution of HLA-DQB1 alleles from 2076 cord blood samples of the Vietnamese cohort.

Human leucocyte antigen (HLA) alleles are very diverse and characterized by ethnicity. To date, information about the frequencies and distributions of HLA alleles among the Vietnamese population is still limited. In this study, HLA-DQB1 alleles of 2076 cord blood units from individuals belonging to Vietnam's Kinh ethnic people were genotyped using Luminex-based polymerase chain reaction sequence-specific oligonucleotide. The results of the study demonstrated that there were 23 alleles on the locus HLA-DQB1. Among those, there were six alleles with high frequencies of over 5%, including DQB1* 03:01 (35.9%), DQB1* 05:01 (12.8%), DQB1* 03:03 (12.2%); DQB1* 06:01 (7.20%), DQB1* 05:02 (6.62%) and DQB1* 02:01 (5.30%) and five rare alleles with low frequencies of below 0.1%. More importantly, this study for the first time reported the presence of two new rare alleles including DQB1* 01:01 and DQB1* 01:02. Conclusively, this study provided significant information about HLA-DQB1 alleles for further investigations and clinical applications.

Association of HLA DRB1-DQB1 Haplotypes with the Risk for Neuromyelitis Optica among South Indians.

Neuromyelitis optica (NMO) is an autoimmune demyelinating disorder, mainly characterized by severe optic neuritis, transverse myelitis and the high levels of antibodies against NMO-immunoglobulin G (IgG) or aquaporin-4 (AQP4). HLA-DR and HLA-DQ alleles within the HLA class II region on chromosome 6p21 are known to play a significant role in several autoimmune diseases including NMO. The rationale of the current case-control study is to explore the association of HLA-DRB1 and HLA-DQB1 alleles with the risk of NMO and its association with the clinical and serological markers. A total of 158 samples (38 NMO cases and 120-age and ethnicity matched controls) were genotyped for the HLA-DRB1 and HLA-DQB1 alleles by using PCR-SSP method. Our analysis showed significant association of HLA-DRB1*10 allele (OR 2.63, 95% CI: 1.18-5.83, p=0.02) with NMO whereas DRB1*14 showed protective role against NMO (OR 0.33: 95% CI: 0.11-0.94, p=0.043). HLA-DRB1*10 allele also showed significant association in patients with NMO-IgG positive antibody (OR 3.28: 95% CI: 1.42-7.5, p=0.006). There was no association of HLA DQB1 alleles with NMO and also with NMO-IgG antibody. Among the haplotypes groups, HLA-DRB1*10-DQB1*05 (OR 2.61, 95% CI: 1.11-6.1, p=0.03), HLA-DRB1*15-DQB1*03 (OR 4.5, 95% CI: 1.81-11.5, p=0.001) were strongly associated with the risk of NMO, whereas DRB1*14-DQB1*05 (OR 0.20, 95% CI: 0.060-0.721, p=0.008) showed negative association with NMO. From this study, it is concluded that the HLA-DRB1*10 and DRB1*10-DQB1*05 and HLA-DRB1*15-DQB1*03 haplotypes may influence the susceptibility to NMO among the South Indians. Additionally we found DRB1*14 allele and DRB1*14-DQB1*05 haplotype showed protective role for NMO.

PB1752: ANALYSIS OF HLA-PEPTIDE BINDING POCKETS IN PATIENTS WITH ACUTE LEUKEMIA UNDERGOING UMBILICAL CORD BLOOD TRANSPLANTATION

Background: Despite a better understanding of the genetic heterogeneity of both acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML), relapse rates remain high and long-term survival is suboptimal. In this context, the association between these malignancies and the human leukocyte antigens (HLA) has been widely studied. The highly polymorphic HLA loci have significance and relevance for disease susceptibility thanks to their peptide-binding grooves-dependent antigen presentation to effector cells. Such processes trigger an algorithm of immune responses based on multiple fine-tuned combinations of amino acid sequence interactions. Thus, the HLA genetic diversity has been a focus of interest in acute leukemia settings as exemplified by studies showing the implication of both HLA class I and II polymorphisms. However, there is scarce data regarding the diversity of peptide-binding pockets per se especially in the context of umbilical cord blood transplantation (UCBT). Aims: To analyze whether variants of HLA-DQB1 and -DRB1 peptide-binding groove pockets 4 and 9 and/or their amino acid positions are associated with the diagnosis of ALL or AML among patients undergoing UCBT. Methods: A retrospective analysis was performed including 849 patients with ALL and AML undergoing an UCBT. Demographics and genotyping data were obtained from the Eurocord database. Pockets and amino acids were imputed from the four-digit HLA genotypes of patients. Easy-HLA was used for haplotype inference when needed. Descriptive statistics were applied. Risk ratios (RRs) and 95% confidence intervals (CI) were estimated by applying log-binomial regression to compare the allelic frequencies between both types of leukemia. Results: ALL and AML were diagnosed in 50.2% and 49.8%, respectively. The median age at UCBT was 8.7 and 17.9 years. Overall, they were mostly pediatric patients (61.8%), males (52%), and in first complete remission (58.7%). From the ten variants analyzed in pocket 9 of the HLA-DQB1 allele, only the variant YYVSY, corresponding to the allele HLA-DQB1*05:02/04, was more frequent in ALL when compared to AML (RR=2.12, 95% CI: 1.30-3.44; p=0.001). Also, within the 21 analyzed pocket 4 variants of the HLA-DRB1 allele, RFDRAY, corresponding to DRB1*16:01/02, was the only variant with a significant higher frequency among ALL patients versus AML patients (RR=3.26, 95% CI: 1.81-5.99; p=0.001). No differences were observed when comparing ALL and AML at either pocket 4 of HLA-DQB1 allele or pocket 9 of HLA-DRB1 allele. Further amino acid analysis revealed that the frequency of serine 57 of the HLA-DQB1 pocket 9 was higher in ALL (RR=2.03, 95% CI: 1.26-3.27; p=0.037). None of the analyzed amino acid positions in HLA-DRB1 pockets was statistically enriched neither in ALL or AML. Summary/Conclusion: Our analyses suggest that specific variants in terms of HLA pockets and amino acids might be unique to ALL. As a result of expressing HLA molecules on their surface, leukemic cells may participate to the disease development and/or to immune evasion. Thus, the immune and genetic expression profile of the leukemic microenvironment has been described as a potential useful biomarker in guiding therapeutic approaches. Interestingly, peptide binding to HLA class II molecules is frequently viewed as a merger of detached anchor residue preferences for pockets 4 and 9. In our study, these associations, at a genotypic level, might be a stepping stone towards analyzing results in acute leukemia after UCBT as there is robust evidence supporting the impact of HLA on important post-transplant outcomes.

HLA Genotyping in Romanian Adult Patients with Celiac Disease, their First-degree Relatives and Healthy Persons.

Celiac disease is characterized by an inappropriate T-cell-mediated response to gluten in small bowel in genetically predisposed individuals, carriers of the DQ2 and/or DQ8 haplotypes of the human leukocyte antigen. The aim of our study was to asses HLA typing in adult patients with celiac disease, in their first degree relatives and in a healthy control group. We conducted a prospective observational study on three cohorts: 117 patients diagnosed with celiac disease, 41 first-degree relatives of celiac patients and 57 asymptomatic healthy volunteers. Low resolution HLA typing forDQ alleles was performed in all study subjects with DNA extracted from peripheral blood, using SSP HLA-DQB1 kit (Innotrain Diagnostik GmbH, Germany).Next Generation Sequencing (NGS) was used only in 18 patients for typing confirmation of DQB1 and DQA1 loci and whole gene sequencing. Prevalence of HLA-DQ2 was significantly higher in the CD group compared to the healthy subjects group (95.6% vs 29.8%, p <0.001), with no statistically significant differences in HLA-DQ8 and combined HLA-DQ2/DQ8 prevalences.Several HLA DQA1 and DQB1 alleles (HLA-DQA1* 05:01, HLA-DQB1*02:01, HLA-DQB1*02:02) and haplotypes (DQA1*02:01-DQB1*02:02,DQA1*05:01-DQB1*02:01) were strongly associated with celiac disease in our group: OR 4.28, 4.28, 4.67 and 5.43 and 4.28 respectively. Predominantly, patients presented with typical symptoms and iron deficiency anemia. 95.5% of them had histological Marsh type modifications ≥3a. A relatively poor response to gluten-free diet was observed and 9.4% developed complications (refractory celiac disease, enteropathy-associated T cell lymphoma, intestinal adenocarcinoma), with a death rate of 6.8%. 23% associated other autoimmune diseases.Screening adherence for 1st degree relatives was very low: only 16%. Familial screening diagnosed 4 cases of asymptomatic celiac disease. 32 relatives (78%) had HLA-DQ2 haplotype, 5 carried HLA-DQ8, 4 didn't carry any risk haplotype. This study demonstrated a higher prevalence of the HLA-DQ2 genotype in patients with celiac disease compared to the healthy population but not of HLA-DQ8 or combined HLA-DQ2/DQ8. Alleles HLA-DQA1* 05:01, HLA-DQB1*02:01, HLA-DQB1*02:02 and haplotypes (DQA1*02:01-DQB1*02:02,DQA1*05:01-DQB1*02:01) were strongly associated with celiac disease in our cohort.

Enhanced Extracellular Transfer of HLA-DQ Activates CD3+ Lymphocytes towards Compromised Treg Induction in Celiac Disease.

Celiac disease (CeD) manifests with autoimmune intestinal inflammation from gluten and genetic predisposition linked to human leukocyte antigen class-II (HLA-II) gene variants. Antigen-presenting cells facilitate gluten exposition through the interaction of their surface major histocompatibility complex (MHC) with the T cell receptor (TCR) on T lymphocytes. This fundamental mechanism of adaptive immunity has broadened upon recognition of extracellular exosomal MHC, raising awareness of an alternative means for antigen presentation. This study demonstrates that conditioned growth media (CGM) previously exposed to monocyte-derived dendritic cells from CeD significantly downregulates the CD3+ lineage marker of control T cells. Such increased activation was reflected in their elevated IL-2 secretion. Exosome localization motif identification and quantification within HLA-DQA1 and HLA-DQB1 transcripts highlighted their significant prevalence within HLA-DQB1 alleles associated with CeD susceptibility. Flow cytometry revealed the strong correlation between HLA-DQ and the CD63 exosomal marker in T cells exposed to CGM from MoDCs sourced from CeD patients. This resulted in lower concentrations of CD25+ CD127− T cells, suggestive of their compromised induction to T-regulatory cells associated with CeD homeostasis. This foremost comparative study deciphered the genomic basis and extracellular exosomal effects of HLA transfer on T lymphocytes in the context of CeD, offering greater insight into this auto-immune disease.

Role of HLA-DQB1 alleles in the risk, signs and symptoms, and severity of celiac disease in a Venezuelan population

Introduction and aimsCeliac disease (CD) is a complex condition, whose main genetic determinant involves HLA molecules, specifically the HLA-DQ2 and/or HLA-DQ8 heterodimers. Nevertheless, the frequency of the alleles encoding those molecules has not been reported in Venezuelan celiac patients. Therefore, the aim of our study was to evaluate the frequency of the HLA-DQB1 alleles in individuals with symptoms suggestive of CD and define the diagnostic markers of the condition in a Venezuelan population. Material and methodsA cross-sectional study included 516 individuals with symptoms suggestive of CD. Molecular typing of the HLA-DQB1 locus was performed using a polymerase chain reaction-sequence-specific oligonucleotide procedure (PCR-SSO). ResultsA total of 58.3% of the individuals with clinical manifestations consistent with CD presented with at least one risk allele (DQB1*0201 and/or DQB1*0302), and the diagnosis was confirmed in 40 of them. The patients with CD had a higher frequency of the DQB1*0201 risk allele (26.25%), followed by the DQB1*0302 (17.5%) allele. There was an association between the presence of risk alleles and the presence of lesions characteristic of CD (P = 0.001), and a correlation was found between the genetic predisposition to develop CD and the presence of anti-tissue transglutaminase antibodies (P = 0.0127). ConclusionsThe results support the role of the DQB1*02 and DQB1*0302 alleles in CD susceptibility and the histologic alterations of the intestinal mucosa, in a Venezuelan population.

Three HLA-DQB1 alleles, DQB1*03:432, DQB1*03:454 and DQB1*03:465 were identified in Chinese individuals.

Compared with HLA-DQB1*03: 01:01:01, the alleles HLA-DQB1*03:432, HLA-DQB1*03:454 and HLA-DQB1*03:465 each show one nucleotide substitution.

New HLA-DQB1 intronic variants detected by next-generation sequencing.

Four novel HLA-DQB1 alleles, -DQB1*02:02:01:08, -DQB1*02:01:01:11, -DQB1*03:01:01:30 and -DQB1*03:01:01:36, characterized in Spanish individuals.

Human leucocyte antigens profiling in Malay female patients with systemic lupus erythematosus: are we the same or different?

ObjectiveSLE is a heterogeneous autoimmune disease, in terms of clinical presentation, incidence and severity across diverse ethnic populations. We investigated the human leucocyte antigens (HLA) profile (ie, HLA-A, HLA-B and...

Association between human leukocyte antigen class II (HLA-DRB and -DQB) alleles and outcome of exposure to Mycobacterium tuberculosis: a cross-sectional study in Nairobi, Kenya.

Introductionhuman leukocyte antigen (HLA) class II alleles play an important role in the early immune response to tuberculosis (TB) by presenting antigenic peptides to CD4+ T cells, hence polymorphisms in those genes can influence the efficiency of the immune response to infection and progression to active disease.Methodsan analytical cross-sectional study of adult pulmonary tuberculosis (PTB) patients at Mbagathi County Hospital, Nairobi and their HHCs. Sociodemographic data were captured on questionnaires and clinical data extracted from patient files. Intravenous blood samples were drawn for interferon-gamma release assay (IGRA) to determine latent tuberculosis infection (LTBI) among HHCs, and for extraction of DNA used in typing of HLA-DQB1 and HLA-DRB1 alleles by PCR sequence specific primer amplification. Chi-square and Fisher's exact test were used to compare the HLA type II allele frequencies of LTBI negative HHCs, LTBI positive HHCs and active TB patients. Logistic regression was used to adjust for HIV status.Resultsthe HLA-DQB1 and HLA-DRB1 alleles were analyzed in 17 PTB and 37 HHCs. Nineteen (19) HHCs were LTBI positive, while 18 were LTBI negative. The frequency of DRB3*1 was 0.17-fold lower [95% CI=0.03-0.83] among PTB patients compared to HHCs before adjustment for HIV status (p=0.048). The frequency of the DRB5*2 allele was significantly higher (p=0.013) among PTB patients (23.5%) compared to HHCS (0.00%). After adjusting for HIV status, the frequency of DRB1*14 was 12-fold higher [95% CI=1.11-138.2] among PTB patients compared to HHCs (p=0.040).Conclusionthe higher frequencies of HLA-DRB5*2 and HLA-DRB1*14 alleles in PTB patients suggest a likely association with progression to active PTB. The higher frequency of HLA-DRB3*1 allele among LTBI negative HHCs shows its likely protective role against M. tuberculosis infection in this population.

Papel de los alelos HLA-DQB1 en el riesgo, signos y síntomas y gravedad de la enfermedad celíaca en la población venezolana

Introduction and aimsCeliac disease (CD) is a complex condition, whose main genetic determinant involves HLA molecules, specifically the HLA-DQ2 and/or HLA-DQ8 heterodimers. Nevertheless, the frequency of the alleles encoding those molecules has not been reported in Venezuelan celiac patients. Therefore, the aim of our study was to evaluate the frequency of the HLA-DQB1 alleles in individuals with symptoms suggestive of CD and define the diagnostic markers of the condition in a Venezuelan population. Material and methodsA cross-sectional study included 516 individuals with symptoms suggestive of CD. Molecular typing of the HLA-DQB1 locus was performed using a polymerase chain reaction-sequence-specific oligonucleotide procedure (PCR-SSO). ResultsA total of 58.3% of the individuals with clinical manifestations consistent with CD presented with at least one risk allele (DQB1*0201 and/or DQB1*0302), and the diagnosis was confirmed in 40 of them. The patients with CD had a higher frequency of the DQB1*0201 risk allele (26.25%), followed by the DQB1*0302 (17.5%) allele. There was an association between the presence of risk alleles and the presence of lesions characteristic of CD (P=.001), and a correlation was found between the genetic predisposition to develop CD and the presence of anti-tissue transglutaminase antibodies (P=.0127). ConclusionsThe results support the role of the DQB1*02 and DQB1*0302 alleles in CD susceptibility and the histologic alterations of the intestinal mucosa, in a Venezuelan population.

Global Meta-Analysis on the Association between Behcet Syndrome and Polymorphisms from the HLA Class I (A, B, and C) and Class II (DRB1, DQB1, and DPB1) Genes.

Behcet syndrome (BS) is a multisystemic perivasculitis whose genetic susceptibility is linked to HLA region. We first meta-analysed all HLA class I and II genes involved in BS susceptibility in all ethnic groups worldwide. We identified 1141 articles and finally included 31 case-control studies after multiple rounds of selection. We analysed frequencies for 24 HLA-A alleles (3 alleles for HLA-A∗26 at four digits), 50 HLA-B alleles (11 alleles for HLA-B∗51 at four digits), 15 HLA-C alleles, 16 HLA-DRB1 alleles, 6 HLA-DQB1 alleles, and 15 HLA-DPB1 alleles. We meta-analysed only HLA allelic frequencies from at least three studies; therefore, we investigated 21 alleles out of 140. Going from 7.00 to 1.6 OR, we found 11 class I alleles conferring risk for BS: B∗51 : 08, B∗51, B∗51 : 01, B∗51 : 02, DQB1∗03, A∗26 : 01, Cw∗14, Cw∗15, Cw∗16, B∗15, and A∗26. Overall, the studies included populations from Europe (Greece, Spain, Italy, Germany, and Ireland), Asia (Korea, China, China Han, and Thailand), Middle East (Israel, Saudi Arabia, and Iran), and Morocco (as no other North-African population was included). We collected a number of ethnical groups sufficient to conduct an ethnic-specific meta-analysis where Europeans showed 11.25 OR for B∗51:08 and Japan 3.50 OR for A∗26 : 01. A remarkable result was that the most frequent HLA − B∗51 two-digit alleles associated with BS were different among populations: HLA − B∗51 : 08 in Europe, HLA − B∗51 : 01 in Turkey, and HLA − B∗51 : 02 in Japan. Overall, we discussed our real-world results with other imputation studies.

HLA-DQA1*04:01 is related to a higher multiple sclerosis lesion load on T2/Flair MRI sequences.

The genetic predisposition to multiple sclerosis (MS) is associated with HLA alleles, especially HLA-DRB1*15:01. To identify associations between findings in magnetic resonance imaging (MRI) and genetic features in a Brazilian cohort of patients with MS. We retrospectively studied data from 95 consecutive patients with MS. Two independent observers who were blinded to the clinical data identified black holes and enhanced lesions on T1 MRI sequences, and counted and measured contrast-enhanced lesions on T2 and Flair (fluid attenuation inversion recovery) sequences. Cases were classified according to lesion size, number, and volume. The HLA-DRB1, HLA-DQB1, and HLA-DQA1 alleles, and the rs4774, rs3087456, rs6897932, rs731236, and rs1033182 single nucleotide polymorphisms were identified by polymerase chain reaction amplification with sequence-specific primers using the One Lambda Inc. Kit, Canoga Park, CA, USA. Patients with the HLA-DQA1*04:01 allele had lesion load (adjusted for age, sex, and MS duration) above median compared with patients with other HLA-DQA1 alleles (p=0.02). There were no differences among all the other HLA alleles and single nucleotide polymorphisms and lesion load. The correlation of the HLA-DQA1*04:01 allele with a higher lesion load on T2/Flair MRI sequences suggests that the presence of this allele is associated with the risk of greater MS severity.

Association of HLA–DRB1, DQA1 and DQB1 alleles and haplotype in Parkinson’s disease from South India

Parkinson’s disease (PD) is a chronic, neurodegenerative motor disease exhibiting familial and sporadic forms. The present study was aimed to elucidate the association of HLA-DRB1*, DQA1* and DQB1* alleles with PD. A total of 105 PD patients and 100 healthy controls were typed by PCR-SSP method. We further carried out high-resolution genotyping for DQB1 and DQA1. Results revealed the increased frequencies of alleles DRB1*04 (OR = 2.36), DRB1* 13 (OR = 4.04), DQA1* 01:04:01 (OR = 4.51), DQB1*02:01 (OR = 2.66) and DQB1*06:03 (OR = 2.65) in PD patients suggesting susceptible associations. Further, decreased frequencies observed for alleles DRB1*10 (OR = 0.34), DRB1*15 (OR = 0.44), DQA1*04:01 (OR = 0.28), DQA1*06:01 (OR = 0.11) and HLA-DQB1*05:01 (OR = 0.37) among patients have suggested protective associations. Significant disease associations were observed for two-locus haplotype such as DRB1*13-DQB1*06:03 (OR = 11.52), DQA1*01:041-DQB1*06:03 (OR = 16.50), DQA1*01:041-DQB1*05:02 (OR = 5.38) and DQA1*04:01-DQB1*06:03 (OR = 3.027). Protective associations were observed for haplotypes DRB1*10-DQB1*05:01 (OR = 0.21), DRB1*15-DQB1*06 (OR = 0.006), DQA1*04:01-DQB1*05:01 (OR = 0.400) and DQA1*04:01-DQB1*05:03 (OR = 0.196). The critical amino acid residue analyses have revealed strong susceptible association for the residues of DQB1 alleles such as: L26, S28, K71, T71 and A74, Y9, S30, D37, I37, A38, A57 and S57; and for the residues of DQA1 alleles such as: C11, F61, I74, and M76. Similarly, amino acid residues such as A13, G26, Y26, A71, S74, L9 and V38 of HLA-DQB1 alleles and residues such as Y11, G61, S74 and L76 of DQA1 alleles showed protective associations. Thus, our study documented the susceptible and protective associations of DRB1*, DQB1 and DQA1 alleles and haplotypes in developing the disease and their influence on longevity of PD patients in south India.

Association of HLA-DPA1, HLA-DPB1, and HLA-DQB1 Alleles With the Long-Term and Booster Immune Responses of Young Adults Vaccinated Against the Hepatitis B Virus as Neonates.

The neonatal hepatitis B vaccination (HBVac) was implemented 35 years ago in Taiwan, but many vaccinees exhibit inadequate long-term vaccine-induced seroprotective hepatitis B surface antibody (anti-HBs) levels. We investigated the association of the human leukocyte antigen (HLA) alleles (DPA1, DPB1, DQA1, and DQB1) with the long-term immunological response to the neonatal HBVac and adolescent booster HBVac in a Taiwanese cohort. We divided 281 Han students (median age 22, age range 17–29 years) into the following groups: (1) Group A (n = 61): anti-HBs titer ≥ 10 mIU/mL at the beginning of the study; (2) Group B (n = 75): anti-HBs level > 1000 mIU/mL after the first booster; (3) Group C (n = 37): anti-HBs level < 10 mIU/mL after the first booster; and (4) Group D (n = 5): anti-HBs level < 10 mIU/mL after three boosters. DQA1, DQB1, DPA1, and DPB1 typing of the participants was performed using sequence-specific oligonucleotides. Associations of HLA alleles and haplotypes with effects on neonatal HBVac and booster HBVac were examined through logistic regression analysis and Fisher’s exact test. A false discovery rate-based measure of significance, the q-value, was used for multiple comparisons, and an association was considered significant if the corresponding q-value was < 0.1. DPA1 alleles were associated with the long-term immunological response to the neonatal HBVac. The estimated odds ratio (OR) of the lack of HBV protective immunity when carrying an additional DPA1*01 and DPA1*02 was 0.36 [95% confidence interval (CI) = 0.17–0.76, p = 0.0076] and 2.39 (95% CI = 1.17–4.87, p = 0.016), respectively. DPB1 and DQB1 alleles were associated with a response to the adolescent booster vaccination. The estimated ORs of being nonresponsive to the first booster when carrying an additional DPB1*05 and DQB1*02 were 2.11 (95% CI = 1.13–3.93, p = 0.019) and 3.73 (95% CI = 1.43–9.71, p = 0.0070), respectively. All DPB1*03 carriers responded to the first booster (p of Fisher’s exact test = 0.0045). In our study, we discovered that HLA-DPA1 was primarily associated with the long-term response of primary infantile HBVac, and HLA-DPB1 and HLA-DQB1 exhibited associations with the HBV booster vaccination.

Next-Generation HLA Sequence Analysis Uncovers Shared Risk Alleles Between Clinically Distinct Forms of Childhood Uveitis.

PurposeClassical alleles of the human leukocyte antigen (HLA) complex have been linked to specific entities of pediatric noninfectious uveitis, yet genetic predisposition encoded by the HLA super-locus across the patient population remains understudied.MethodsWe performed next-generation full-length sequencing of HLA-A, HLA-B, HLA-C, HLA-DPB1, HLA-DQB1, and HLA-DRB1 in 280 cases. Dense genotype data from 499 Dutch controls from Genome of the Netherlands were imputed using an HLA-specific reference panel (n = 5225 samples from European ancestry). Cases and controls were compared using logistic regression models adjusting for sex.ResultsIn total, 179 common and rare alleles were detected. Considering all cases and controls, HLA-DQB1*04:02 and HLA-DRB1*08:01 were identified as the principal HLA association, which was mainly driven by 92 cases with juvenile idiopathic arthritis-associated uveitis (JIA-U). The HLA-DQB1*04:02-HLA-DRB1*08:01 haplotype was also the primary association for the phenotypically similar idiopathic chronic anterior uveitis without arthritis (CAU). Also, HLA-DQB1*05:03 was an independent risk allele for CAU, but not in JIA-U. Analysis of 185 cases with other forms of uveitis revealed HLA-wide associations (P < 2.79 × 10−4) for HLA-DRB1*01:02, HLA-DRB1*04:03, and HLA-DQB1*05:03, which could be primarily attributed to cases with panuveitis. Finally, amino acid substitution modeling revealed that aspartic acid at position 57 that distinguishes the risk allele HLA-DQB1*05:03 (for CAU and panuveitis) from nonrisk alleles, significantly increased the binding capacity of naturally presented ligands to HLA-DQ.ConclusionsThese results uncovered novel shared HLA associations among clinically distinct phenotypes of pediatric uveitis and highlight genetic predisposition affecting the antigen presentation pathway.

Relevance of autoantibody profile with HLA-DRB1 and -DQB1 alleles in a group of Iranian systemic lupus erythematosus patients

BackgroundOne of the most relevant genetic components in systemic lupus erythematosus (SLE) is human leukocyte antigen (HLA) gene complex which plays a central role in autoimmune responses. This study aimed to explore the associations of HLA-DRB1/-DQB1 alleles and haplotypes with SLE risk and the appearance of autoantibodies in SLE disease. MethodsA total of 127 SLE patients and 153 ethnically matched healthy controls were enrolled. HLA-DRB1 and HLA-DQB1 alleles were determined by PCR-SSP method and then HLA alleles and haplotypes frequencies were compared between two groups and among the patients in terms of autoantibodies spectrum. ResultsWe found that HLA-DRB1*03 and HLA-DRB1*16 alleles were significantly associated with increased risk (P = 0.008, PC=0.05 and P = 0.002, PC=0.02 respectively) and DRB1*01 conferred a potential protective role for disease (P = 0.03, PC=0.13). Similar associations were observed at haplotype level; DRB1*03~DQB1*02 (OR1.91,P = 0.01, PC=0.08), DRB1*16~DQB1*05 (OR3.65,P = 0.004,PC=0.06) and DRB1*01~DQB1*05 (OR0.36,P = 0.04, PC=0.22). Remarkably, we observed significantly associations of DRB1*03 with the appearance of anti-SSA/Ro (PC=0.02), anti-SSB/La (PC=0.002) and anti-coagulant (P = 0.007), DRB1*15 with anti-SSA/Ro (PC=0.04), DRB1*16 with anti-Sm (PC=0.02), DRB1*04 with anti-β2gpI (PC=3 * 10−5), anti-cardiolipin (P = 0.002) and rheumatoid factor (P = 0.004) and DRB1*13 with anti-Sm (PC=0.02) and anti-β2gpI (PC=0.01) antibodies. Also, negative associations of DRB1*04 with anti-Sm, anti-SSA/Ro, DQB1*03 with anti-Sm and DRB1*11 with anti-Sm and anti-β2gpI were observed. ConclusionsWe identified DRB1*03 and DRB1*16 as risk alleles and DRB1*01 as a potential protective allele for SLE disease. More importantly, we found a close link between genetic susceptibility for SLE and autoantibodies status that was more evident for DRB1*03 allele.