Search

Objectives: Nasal polyposis (NP) is a common and recurrent condition of the sinonasal cavity which has significant impact on patients' quality of life. NP pathophysiology involves a complex interplay of genetic, environmental, and immunological factors. Several studies have explored the association between human leukocyte antigen (HLA) class II alleles and NP, but the results have been conflicting. The aim of this meta-analysis is to investigate the association between HLA class II alleles, specifically HLA-DQA1, HLA-DQB1, and HLA-DRB1and NP risk. Methods: A systematic review was conducted using electronic databases, including PubMed, Google Scholar, and Cochrane Library, to identify studies investigating the association between HLA class II alleles and NP. Eligible studies were identified by specific inclusion and exclusion criteria. The odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the association between HLA class II alleles and NP risk. A random-effects model was used to calculate the pooled OR and corresponding 95% CI, and a study required a heterogeneity assessment value I 2 < 25% to be considered for analysis. Study design: Meta-analysis. Results: A total of four studies were included in this meta-analysis, involving a total of 258 NP alleles and 802 control alleles. The analysis indicated that DQA1*0201 (OR = 3.08, 95% CI [1.70, 5.59]) and DRB1*7 (OR = 2.04, 95% CI [1.14, 3.66]) were significantly associated with increased risk of NP. The analysis of the NP risk alleles DQA1*0201 and DRB1*7 had an I2 < 0% representing low heterogeneity. Sensitivity analysis with LFK indices showed minor asymmetry in either allele. Conclusions: This meta-analysis provides evidence that the HLA-DQA1*0201 and HLA-DRB1*7 alleles are risk factors for the development of NP. These findings could contribute to a better understanding of the genetic predisposition of NP and may have implications for the development of novel approaches for the prevention and treatment of this condition. [ABSTRACT FROM AUTHOR]

The goal of the current study was to determine the high-resolution frequencies of the HLA-DRB1 alleles among the analyzed Romanian cohort of healthy stem cell donors. Using Next Generation Sequencing (NGS), we estimated class II HLA-DRB1 allele frequencies to a 6-digit resolution through HLA typing in a Romanian cohort of healthy individuals. The study for HLA genotyping included 420 willing donors from the National Registry of Voluntary Hematopoietic Stem Cell Donors (RNDVCSH). In 2020 and 2021, peripheral blood samples were collected and transported to the Fundeni Clinical Institute. We used the Immucor Mia Fora NGS MFlex kit for HLA genotyping. Forty-one different alleles were detected in 420 analyzed samples, out of which the most frequent HLA-DRB1 alleles were DRB1*16:01:01 (12.6%), DRB1*11:04:01 (12.1%) and DRB1*03:01:01 (12%). The HLA-DRB1*11:01:02 and -DRB1*08:04:01, -DRB1*05:01:01, -DRB1*13:05:01, -DRB1*14:07:01, -DRB1*09:01:02, -DRB1*11:02:01, -DRB1*04:07:01, -DRB1*15:03:01, -DRB1*03:02:01, -DRB1*04:06:02, -DRB1*04:08:01, -DRB1*14:05:01 were identified only once. The results revealed similarities with countries belonging to the Eastern Europe, the Balkans and the Caucasus regions. Further studies on larger Romanian cohorts are needed for confirming the current results.

Genome-wide association studies (GWAS) of Alzheimer's disease (AD) have identified a large number of susceptibility genes, but most of AD heritability remains unexplained, implying the existence of additional genes. Furthermore, the majority of the GWAS have been conducted in people of European descent, and the genes important for AD susceptibility in people of African descent have been underexplored. In this hypothesis-generating prospective cohort study, we genotyped 191 African Americans (AAs) from three longitudinal cohorts on aging for the IgG3 allotype GM6, which is expressed exclusively in people of African descent, and assessed its interaction with IGHG, FCGRIIB, and HLA-DRB1 genes. Cox proportional hazards modeling showed that GM6 by itself was not significantly associated with AD development. However, there was evidence of epistatic interaction: The risk of developing AD associated with GM6 positivity was significantly different (p = 0.0098) in non-GM17/GM17 participants compared with GM 17/GM17 participants. Specifically, in non-GM17/GM17 participants, the risk of AD was over fourfold higher in GM6-positive participants compared with GM 6-negative participants (HR = 4.63). Similarly, risk of developing AD associated with GM6 positivity was marginally different in non-FCGRIIB TT participants compared with FCGRIIB TT participants. In non-FCGRIIB TT participants, the risk of developing AD was over twofold higher in GM6-positive participants compared with GM6-negative participants (HR = 2.44). This is the first report suggesting that immunoglobulin GM allotypes might play a role in AD etiology among AAs; however, since this was largely a hypothesis-generating study, replication in larger cohorts would be required to confirm this finding. [ABSTRACT FROM AUTHOR]

Background and Objectives This study looked at the frequency of HLA alleles and their genetic diversity in specific Iranian ethnic groups. This is important for the successful transplantation of hematopoietic stem cells. Materials and Methods In this descriptive study, HLA-DRB1 alleles were determined in low resolution level for donors using the PCR-SSP method. By using the HLA lab data and the stem cell donors' information in Iranian Blood Transfusion Organization, the ethnic and HLA information from the Gilak (n = 510, 24.70%), Lur (n = 465, 22.53%), Kurd (n = 719, 34.84%), and Arab (n = 370, 17.93%) ethnicities were collected and analyzed. The relationship between alleles and ethnicity was examined, and a statistically significant relationship (p < 0.05) between the frequency of alleles in the studied ethnic groups was evaluated using the chi-square test. Results The low frequency allelic groups related to HLA-DRB1 were HLA-DRB1*09 (0.6%), HLADRB1*12 (0.8%), and HLA-DRB1*08 (1.6%). Allelic groups with higher frequency included HLA-DRB1*11 (22.7%), HLA-DRB1*03 (11.8%), HLA-DRB1*15 (11.7%), and HLADRB1*04 (11.1%). Among the allelic groups of HLA-DRB1, the frequency of 9 HLA-DRB1 allelic groups showed significant differences in the studied populations. Conclusions The frequency of several allelic groups showed significant differences among Iranian ethnicities. Identifying similarities and differences in the frequency of HLA alleles among Iranian ethnicities can help not only expand the pool of donors in registries but also assist in planning for providing of hematopoietic stem cell donors for patients from different Iranian ethnic groups. [ABSTRACT FROM AUTHOR]

Abstract The strongest genetic risk factor for rheumatoid arthritis (RA) has been known as HLA-DRB1 based on amino acid positions 11, 71, and 74. This study analyzed the association between specific HLA-DRB1 locus and treatment response to abatacept or TNF inhibitors (TNFi) in patients with seropositive RA. A total of 374 Korean RA patients were treated with abatacept (n = 110) or TNFi (n = 264). Associations between HLA-DRB1 and treatment response after 6 months were analyzed using multivariable logistic regression. Seropositive RA patients with HLA-DRB1 shared epitope (SE) had a favorable response to abatacept (OR = 3.67, P = 0.067) and an inversely associated response to TNFi (OR 0.57, P = 0.058) based on EULAR response criteria, but the difference was not statistically significant in comparison to those without SE. In analyses using amino acid positions of HLA-DRB1, a significant association was found between valine at amino acid position 11 of SE and good response to abatacept (OR = 6.46, P = 5.4 × 10–3). The VRA haplotype also showed a good response to abatacept (OR = 4.56, P = 0.013), but not to TNFi. Our results suggest that treatment response to abatacept or TNFi may differ depending on HLA-DRB1 locus in seropositive RA, providing valuable insights for selecting optimal therapy.

Background and Objectives: Chlamydia trachomatis (C. trachomatis) represents one of the most prevalent bacterial sexually transmitted diseases. This study aims to explore the relationship between HLA alleles/genotypes/haplotypes and C. trachomatis infection to better understand high-risk individuals and potential complications. Materials and Methods: This prospective study recruited participants from Transylvania, Romania. Patients with positive NAAT tests for C. trachomatis from cervical/urethral secretion or urine were compared with controls regarding HLA-DR and -DQ alleles. DNA extraction for HLA typing was performed using venous blood samples. Results: Our analysis revealed that the presence of the DRB1*13 allele significantly heightened the likelihood of C. trachomatis infection (p = 0.017). Additionally, we observed that individuals carrying the DRB1*01/DRB1*13 and DQB1*03/DQB1*06 genotype had increased odds of C. trachomatis infection. Upon adjustment, the association between the DRB1*01/DRB1*13 genotype and C. trachomatis remained statistically significant. Conclusions: Our findings underscore the importance of specific HLA alleles and genotypes in influencing susceptibility to C. trachomatis infection. These results highlight the intricate relationship between host genetics and disease susceptibility, offering valuable insights for targeted prevention efforts and personalized healthcare strategies. [ABSTRACT FROM AUTHOR]

Background: Previous genome-wide association studies investigating the relationship between the HLA-DRB1 and the risk of Parkinson’s disease (PD) have shown limited racial diversity and have not explored clinical heterogeneity extensively. Methods: The study consisted of three parts: a case–control study, a crosssectional study, and a longitudinal cohort study. The case–control study included 477 PD patients and 477 healthy controls to explore the relationship between rs660895 and PD susceptibility. The cross-sectional study utilized baseline data from 429 PD patients to examine the correlation between rs660895 and PD features. The longitudinal study included 388 PD patients who completed a 3-year follow-up to investigate the effects of rs660895 on PD progression. Results: In the case–control study, HLA-DRB1 rs660895-G allele was associated with a decreased risk of PD in allele model (adjusted OR=0.72, p  =  0.003) and dominant model (AG  +  GG vs. AA: adjusted OR  =  0.67, p  =  0.003). In the crosssectional analysis, there was no association between rs660895 and the onset age, motor phenotype, or initial motor symptoms. In the longitudinal analysis, PD patients with the G allele exhibited a slower progression of motor symptoms (MDS-UPDRS-III total score: β  = −5.42, p  <  0.001, interaction p time × genotype  <  0.001) and non-motor symptoms (NMSS score: β  = −4.78, p  =  0.030, interaction p time × genotype  <  0.001). Conclusion: Our findings support HLA-DRB1 rs660895-G allele is a protective genetic factor for PD risk in Chinese population. Furthermore, we also provide new evidence for the protective effect of rs660895-G allele in PD progression. [ABSTRACT FROM AUTHOR]

The strongest genetic risk factor for rheumatoid arthritis (RA) has been known as HLA-DRB1 based on amino acid positions 11, 71, and 74. This study analyzed the association between specific HLA-DRB1 locus and treatment response to abatacept or TNF inhibitors (TNFi) in patients with seropositive RA. A total of 374 Korean RA patients were treated with abatacept (n = 110) or TNFi (n = 264). Associations between HLA-DRB1 and treatment response after 6 months were analyzed using multivariable logistic regression. Seropositive RA patients with HLA-DRB1 shared epitope (SE) had a favorable response to abatacept (OR = 3.67, P = 0.067) and an inversely associated response to TNFi (OR 0.57, P = 0.058) based on EULAR response criteria, but the difference was not statistically significant in comparison to those without SE. In analyses using amino acid positions of HLA-DRB1, a significant association was found between valine at amino acid position 11 of SE and good response to abatacept (OR = 6.46, P = 5.4 × 10–3). The VRA haplotype also showed a good response to abatacept (OR = 4.56, P = 0.013), but not to TNFi. Our results suggest that treatment response to abatacept or TNFi may differ depending on HLA-DRB1 locus in seropositive RA, providing valuable insights for selecting optimal therapy. [ABSTRACT FROM AUTHOR]

Background: Keloids and hypertrophic scars are abnormal fibro-proliferative lesions. Associations between genes, the human leukocyte antigen (HLA) system in particular, and keloids have been studied in various ethnic groups but not in Thais. Objective: To investigate the association of HLA alleles with keloids and hypertrophic scars in Thais. Materials and Methods: The present study employed a retrospective case-control design. Scar assessment was performed on 139 kidney donors who underwent nephrectomy at Ramathibodi Hospital between January 2008 and December 2015. The wound scars after nephrectomy were evaluated and graded by a plastic surgeon using the modified Vancouver Scar Scale. Kidney donors who were unable to communicate well or who had autoimmune diseases or complications from surgery were excluded from the study. The diagnosis of a keloid scar, hypertrophic scar, and flat scar was made by clinical criteria. The donors were categorized into groups with three scar types, flat as the control group, hypertrophic, and keloid. The associations between the frequencies of HLA antigen with hypertrophic scar and keloids were measured with an odds ratio using logistic regression analysis. Results: Of the 139 living kidney donors, 15 (10.8%) had keloids, 46 (33.1%) had hypertrophic scars, and 78 (56.1%) had flat scars. Sixty-one HLA-A, -B, -DRB1, and -DQB1 alleles were evaluated in the present study. Compared with controls, the allele frequency of HLA-DRB1*15 was significantly higher in the keloid group at 43.33% versus 24.36% (odds ratio 2.37, 95% confidence interval 1.06 to 5.33, p=0.036). No significant association between HLA alleles and hypertrophic scars was found. Conclusion: The present study demonstrated the positive association of HLA-DRB1*15 with keloids in Thai individuals. The HLA-DRB1*15 could be a susceptibility factor for the development of keloids. [ABSTRACT FROM AUTHOR]

Studies concerning the genetic background of IgA vasculitis (IgAV), a small-vessel vasculitis occurring predominantly in childhood, have confirmed that the HLA-DRB1 gene showed a strong association with disease susceptibility. The objective was to investigate human leukocyte antigen (HLA) polymorphisms among Croatian patients with IgAV and their influence on disease susceptibility and clinical heterogeneity. Thus, 130 children with IgAV and 202 unrelated healthy individuals were enrolled in the study. Genomic DNA was extracted from whole peripheral blood, and HLA-A, -B, -DRB1 and -DQB1 gene polymorphism analysis was performed. HLA-A*03 (21.4% vs. 12.38%, p = 0.0092), HLA-B*37 (2.9% vs. 0.2%, p = 0.0054) and HLA-DRB1*12 (3.1% vs. 0.7%, p = 0.0216) alleles were significantly more frequent in IgAV patients than in controls. High-resolution typing revealed significantly higher frequency of HLA-DRB1*10:01 and -DRB1*11:03 among IgAV patients with gastrointestinal manifestations of the disease in comparison to controls (p = 0.0021 and p = 0.0301, respectively), while HLA-DRB1*14:01P occurred significantly more often in the group of patients who developed nephritis during the course of the disease (17.5% vs. 4.5%, p = 0.0006). Our results demonstrated that there is an association of HLA-A*03, HLA-B*37 and HLA-DRB1*12 alleles with susceptibility to IgAV in the examined Croatian pediatric population. Studies which aim to determine the HLA profile may contribute to the elucidation of the genetic background of autoimmune diseases, including IgAV. [ABSTRACT FROM AUTHOR]

Compared with HLA‐DRB1*08:03:02:01, the alleles HLA‐DRB1*08:03:13 and HLA‐DRB1*08:119 each show one nucleotide substitution, respectively. [ABSTRACT FROM AUTHOR]

The novel allele HLA‐DRB1*03:210 differs from HLA‐DRB1*03:01:01:01 by one non‐synonymous nucleotide substitution in exon 3. [ABSTRACT FROM AUTHOR]

Objectives: HLA-DRB1 is associated with an increased risk of cardiovascular disease in patients with rheumatoid arthritis (RA). This study aimed to determine the effect of HLA-DRB1 on atherosclerotic cardiovascular disease (ASCVD) using a novel mouse model. Methods: Mice transgenic for HLA-DRB1*04:01 (DR4tg) were crossed with low density lipoprotein receptor knock-out (Ldlr−/−) mice that develop atherosclerosis when fed a high fat, high cholesterol (HFHC) diet. Male and female DR4tgLdlr−/− (n = 48), Ldlr−/− (n = 24), DR4tg (n = 24), and C57Bl/6 (B6) background (n = 24) mice were fed HFHC or regular diet (RD) for 12 weeks. Blood samples were analyzed for serum lipoproteins using a colorimetric assay. C-reactive protein (CRP) and oxidized LDL (OxLDL) were measured using ELISA. Atherosclerosis in the aortas was assessed using the lipid stain, Sudan IV. The presence of citrulline in atherosclerotic plaque was determined by immunohistochemistry. Results: Sera low-density lipoprotein cholesterol (LDL-C) levels were higher in HFHC-fed Ldlr−/− versus DR4tgLdlr−/−-; p = 0.0056, but the aortic plaque burden and degree of citrullination in the plaque were similar for these two strains. The ratio of pro-atherogenic OxLDL to LDL levels was higher in DR4tgLdlr−/− than Ldlr−/−mice; p = 0.0017. All mice had an increase in CRP when fed a HFHC diet, most pronounced for DR4tgLdlr−/−; p = 0.0009. There were no significant sex differences for DR4tgLdlr−/− mice; however, male Ldlr−/− mice had worse atherosclerosis. B6 and DR4tg mice did not have significant elevations in serum cholesterol levels and did not develop atherosclerosis. Conclusions: Expression of HLA-DRB1 resulted in an elevation of OxLDL and a reduction in the male bias for atherosclerosis, mimicking what is observed in RA.

Evidence concerning the individual differences in neutralizing antibody responses after receiving the COVID-19 vaccine remains lacking. In this study, we collected the serum and Peripheral blood mononuclear cells(PBMC) of 16 subjects who had never suffered from COVID-19 before during the course of two vaccine doses. Microneutralization assay is used to determine the immune response intensity of vaccine subjects. we revealed the change trend of TCR diversity using T cell receptor (TCR) sequencing. Then, we analyzed the correlation between HLA class II allele frequencies and the intensity of immune response. Finally, we identified several CDR3 sequences related to the intensity of the immune response. We analyzed the differences in D50 (DD50) between different time points, and found that there were two patterns in the change trend of TCR diversity, and the increased diversity group has stronger immune response. The inactivated vaccine is different from the mRNA vaccine against the spike protein, resulting in differences in TCR repertoire response patterns and antibody responses, which are related to HLA-DRB1 * 09:01. The presence of specific CDR3 sequences in the increased diversity group, rather than gene usage of the VJ gene, determines the intensity and persistence of neutralizing antibody titers. Finally, We identified the different response patterns of the human TCR repertoire to inactivated vaccines. The pattern with increased diversity is more likely to appear strong and more lasting immune response. • This article focuses on vaccine injection subjects who have never been infected with COVID-19. • The correlation between immune response and TCR was longitudinal observed at different time points. • HLA-DRB1*09:01 was found to be related to the intensity of immune response. • TCR clonotypes related to immune response intensity were screened out. [ABSTRACT FROM AUTHOR]

• The existence of subphenotypes common to several autoimmune diseases (AIDs) suggests a shared physiopathology. Multiple autoimmune syndrome (MAS) is the paradigm of polyautoimmunity. • This study confirmed HLA-DRB1*03 as a risk factor and HLA-DRB1*13 as a protection factor for AIDs. HLA-DRB1*14 could be a protection factor. • HLA-DRB1*07 might have a protective role against multiautoimmunity in SLE patients. HLA-DRB1*15 could be a risk factor for sjögren's syndrome. • Anti-U1RNP could be used to ascertain probability of developing a second connective tissue disease on patients with an established AID. • The coexistence of AIDs contributes to a more severe disease course. The existence of subphenotypes common to several autoimmune diseases (AIDs) suggests a shared physiopathology - autoimmune tautology. Multiple Autoimmune Syndrome (MAS) - the coexistence of three or more AIDs in one person-, best illustrates that polyautoimmunity is more than a coincidence. Characterize and compare the monoautoimmune and MAS patients. Understand if clustering of AIDs leads to differences in disease severity, autoantibodies expression or genetic polymorphisms that could be markers for polyautoimmunity. Currently adult patients were selected from unit cohort. MAS was assumed when ≥3 AIDs were present. 343 patients were included after exclusion criteria: having two AIDs or undetermined diagnosis. Clinical and immunological data were collected from medical files. HLA-DRB1 was genotyped by PCR-SSP methodology and PTPN22(rs2476601) polymorphisms by TaqMan Real Time PCR. Data were analysed using Chi-Square, Fisher's exact tests and logistic regression. Odds ratios (OR) and 95% confidence intervals were calculated. In comparison with control population: HLA-DRB1*03 in study cohort (OR=3.68, p <0.001) and in monoautoimmune SLE (OR=2.79, p <0.001) and SjS (OR=8.27, p <0.001); HLA-DRB1*15 in monoautoimmune SjS (OR=2.39, p = 0.011); HLA-DRB1*16 in MAS SLE (OR=2.67, p = 0.031); PTPN22_T in all groups except monoautoimmune SjS and triple positive systemic MAS. HLA-DRB1*11 in study cohort (OR=0.57, p = 0.013), in MAS SLE (OR=0.39, p = 0.031) and monoautoimmune SjS (OR=0.10, p = 0.005); HLA-DRB1*13 in study cohort (OR=0.52, p = 0.001) and in monoautoimmune SLE (OR=0.53, p = 0.009) and SjS (OR=0.38, p = 0.031); HLA-DRB1*14 in study cohort (OR=0.32, p = 0.013) and monoautoimmune SLE (OR=0.21, p = 0.021); SLE group: HLA-DRB1*07 frequency was higher in monoautoimmune patients (OR=0.43, p = 0.023). MAS patients had significantly more NPSLE (OR=2.99, p <0.001), subacute cutaneous lesions (OR=2.30, p = 0.037), muscle&tendon (OR=2.00, p = 0.045), and haematological (OR=3.18, p = 0.006) involvement and Raynaud's (OR=2.94, p <0.001). SjS group: MAS patients had more frequently cryoglobulins (OR=2.96, p = 0.030), low complement (OR=2.43, p = 0.030) and Raynaud's (OR=4.38, p <0.001); monoautoimmune patients had more parotid enlargement (OR=0.12, p <0.001). APS group: MAS patients had more non-thrombotic manifestations (OR=4.69, p = 0.020) and Raynaud's (OR=9.12, p <0.001). Triple positive systemic MAS (SLE+SjS+APS) had more frequently severe kidney involvement (OR=11.67, p = 0.021) and CNS thrombosis (OR=4.44, p = 0.009). Anti-U1RNP increased frequency was transversally attributable to MAS. The coexistence of AIDs contributes to a more severe disease course. We confirmed previously established genetic risk and protection factors and suggest a new protective one - HLA-DRB1*14. HLA-DRB1*07 and anti-U1RNP could be markers for mono and polyautoimmunity, respectively; HLA-DRB1*13 could be a predictor for vascular risk in patients with multiple AIDs. PTPN22(rs2476601) polymorphism could be associated with less severe disease. [ABSTRACT FROM AUTHOR]

The novel HLA‐DRB1*16:79 allele, first described in an individual from Brazil. [ABSTRACT FROM AUTHOR]

Background and Objectives: Chlamydia trachomatis (C. trachomatis) represents one of the most prevalent bacterial sexually transmitted diseases. This study aims to explore the relationship between HLA alleles/genotypes/haplotypes and C. trachomatis infection to better understand high-risk individuals and potential complications. Materials and Methods: This prospective study recruited participants from Transylvania, Romania. Patients with positive NAAT tests for C. trachomatis from cervical/urethral secretion or urine were compared with controls regarding HLA-DR and -DQ alleles. DNA extraction for HLA typing was performed using venous blood samples. Results: Our analysis revealed that the presence of the DRB1*13 allele significantly heightened the likelihood of C. trachomatis infection (p = 0.017). Additionally, we observed that individuals carrying the DRB1*01/DRB1*13 and DQB1*03/DQB1*06 genotype had increased odds of C. trachomatis infection. Upon adjustment, the association between the DRB1*01/DRB1*13 genotype and C. trachomatis remained statistically significant. Conclusions: Our findings underscore the importance of specific HLA alleles and genotypes in influencing susceptibility to C. trachomatis infection. These results highlight the intricate relationship between host genetics and disease susceptibility, offering valuable insights for targeted prevention efforts and personalized healthcare strategies.

The aim of this study was to determine the Human Leukocyte Antigen (HLA) class II (DRB1 and DQB1) alleles and haplotype frequency in Rheumatoid Arthritis (RA) in the Sudanese population. The frequency of HLA-DRB1 and -DQB1 alleles and DRB1-DQB1 haplotypes were determined in 122 RA patients and 100 controls. HLA alleles were genotyped by the polymerase chain reaction-sequence specific primers (PCR-SSP) method. In RA patients, HLA-DRB1*04 and *10 alleles were high in frequency (9.6% vs 14.2%, P = 0.038 and P = 0.042, respectively), and dependently on anti-citrullinated protein antibodies (ACPAs) seropositivity (P = 0.044 and P = 0.027, respectively). In contrast, the frequency of the HLADRB1* 07 allele was significantly low in patients than in controls (11.7% vs 5.0%, P = 0.010). Moreover, the HLA-DQB1*03 allele was strongly associated with RA risk (42.2%, P = 2.2x10-8), whereas, HLA-DQB1*02 and *06 showed protective effects against RA (23.1% and 42.2%, P = 0.024 and P = 2.2x10-6, respectively). Five different HLA haplotypes, DRB1*03-DQB1*03 (P = 0.00003), DRB1*04-DQB1*03 (P = 0.00014), DRB1*08-DQB1*03 (P = 0.027), DRB1*13-DQB1*02 (P = 0.004), and DRB1*13-DQB1*03 (P = 3.79x10-8) were significantly associated with RA risk, while 3 protective haplotypes, DRB1*03-DQB1*02 (Pc = 0.008), DRB1*07-DQB1*02 (Pc = 0.004), and DRB1*13-DQB1*06 (Pc = 0.02) were identified. This is the first study determining the association between HLA class II alleles and haplotypes and RA risk in our population. [ABSTRACT FROM AUTHOR]

Background: Rheumatoid arthritis (RA) is an inflammatory immune disease that primarily affects the joints and has its root cause in immune system malfunction. It is unclear what causes RA, but research points to a combination of genetic predisposition, environmental exposures, and microbial infections. Objectives: This study aimed to illustrate the relationship between RA and Mycoplasma pneumoniae. Materials and Methods: The work was performed on 50 RA subjects of various ages, ranging from 25 to 75 years of age, who were treated at the rheumatology clinic in the city of Medical Marjan between February 2022 and October 2022. Blood samples were used for DNA extraction. VEGF-A.HLA-DRB1 and mycoplasma were detected by enzyme-linked immunosorbent assay. Results: The results show a significant increase in the serum concentration level of VEGF-A in RA patients infected with M. pneumoniae as compared to healthy individuals, but the results of RA patients with M. pneumoniae infections and RA patients without M. pneumoniae infections were nonsignificant (P > 0.05). The results showed a significant increase in the serum concentration level of HLA-DRB1 in the RA patients infected with M. pneumoniae as compared to the RA patients noninfected with M. pneumoniae and healthy individuals. Conclusions: In HLA-DRB1, the SNP rs35445101 shows that A allele behavior as recessive pathogenic allele in which the individual that carries AA genotype has a susceptibility to the disease 9.75 fold compared to an individual that carries GG and AG genotype (odds ratio 9.75 confidence interval 95% 1.19–79.78).

Taking into account the significance of the HLA complex in the inflammatory and immune responses, we can assume that the potential for limiting or developing pathology in the next generation will be determined at the stage of selection of certain alleles in the spousal genotype.The aim. To study the role of HLA assortativity in couples with healthy children and couples with children with congenital heart diseases (CHD) through the prism of immunogenetic mechanisms of mutual olfactory choice.Materials and methods. We studied the distribution of HLA-DRB1 alleles in married couples with healthy children and with children having CHD. To identify the associations of HLA-DRB1 alleles with odor preferences, we also studied the group included young males and females. HLA-DRB1 gene typing was carried out in all participants.Results. The combination of HLA-DRB1 alleles in couples with healthy children was similar to the combination of these alleles in the mutual olfactory sympathy between unfamiliar young males and females. Allele combinations in the spouses from the experimental group differ from the group of random selection. The frequency of matches for HLA-DRB1 alleles in married couples with children having CHD without was significantly higher than in the control group.Conclusion. The first stage of selection, associated with olfactory selection, is aimed to the whole population, and it is significantly manifested in the control group (married couples with healthy children). At the same time, in the experimental group (couples with children having CHD), some deviations from the main selection were discovered. Generally, specific HLA-DRB1 allele combinations obtained on the basis of olfactory assessments, indicate the involvement of HLA molecules in pheromone reception.

By presenting antigen peptides, HLA‐DRB1 plays an important role in the immune system. However, the allele frequency of HLA‐DRB1 exon 2 across China has not been comprehensively studied, especially in minority populations. We sampled 3757 individuals from 59 population. The HLA‐DRB1 region from 212 to 463 bp (NM_002124.4 exon 2) in each population was sequenced by Sanger sequencing and genotyped via SBTengine® software, and the allele frequency was calculated by GenAlEx 6.5. Eighty‐two DRB1 alleles were identified. The expected heterozygosity of DRB1 was lower in the south than in the north, which was inconsistent with the Y chromosome and mitochondrial DNA results. The Mantel test and nonparametric correlation analysis showed that the correlations of the genetic distance with geographical distance and of DRB1 allele frequencies with latitude weakened after the southern and northern groups were considered separately. Principal coordinate analysis showed that populations speaking the same languages were not codistributed. Compared with other genetic markers, the distribution of DRB1 seems less affected by geographic distance and ethnic origin. Local factors such as gene flow with neighbouring populations, geographic isolation or natural selection are important forces shaping the DRB1 gene pool of local populations. [ABSTRACT FROM AUTHOR]

The HLA system plays a significant role via the regulation of the immune system and contributes to the progression and protection of many diseases. In our previous study, several HLA‐DRB1 alleles were found to have a susceptible or protective role toward infection and neuroinvasion of West Nile Virus (WNV) in the Greek population. As expected, the majority of polymorphic positions are located in the peptide‐binding region of the molecule. In the present work, the structure of these alleles was studied in silico, to examine the effect of polymorphism on the conformation of DRB1 proteins, with the aspect of WNV association. More specifically, molecular dynamics simulations were used for structural prediction of 23 available alleles. These modeled alleles were evaluated using root‐mean‐square deviation (RMSD) and root‐mean‐square fluctuation analysis. Low RMSD values indicate that different alleles have similar structures. Furthermore, low fluctuation was observed in the peptide‐binding region between alleles with the higher and the lowest RMSD values. These findings indicate that probably variable residues do not affect the behavior of DRB1 alleles in WNV disease, by causing structural differences between them. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine the Human Leukocyte Antigen (HLA) class II (DRB1 and DQB1) alleles and haplotype frequency in Rheumatoid Arthritis (RA) in the Sudanese population. The frequency of HLA-DRB1 and -DQB1 alleles and DRB1-DQB1 haplotypes were determined in 122 RA patients and 100 controls. HLA alleles were genotyped by the polymerase chain reaction-sequence specific primers (PCR-SSP) method. In RA patients, HLA-DRB1*04 and *10 alleles were high in frequency (9.6% vs 14.2%, P = 0.038 and P = 0.042, respectively), and dependently on anti-citrullinated protein antibodies (ACPAs) seropositivity (P = 0.044 and P = 0.027, respectively). In contrast, the frequency of the HLA-DRB1*07 allele was significantly low in patients than in controls (11.7% vs 5.0%, P = 0.010). Moreover, the HLA-DQB1*03 allele was strongly associated with RA risk (42.2%, P = 2.2x10-8), whereas, HLA-DQB1*02 and *06 showed protective effects against RA (23.1% and 42.2%, P = 0.024 and P = 2.2x10-6, respectively). Five different HLA haplotypes, DRB1*03-DQB1*03 (P = 0.00003), DRB1*04-DQB1*03 (P = 0.00014), DRB1*08-DQB1*03 (P = 0.027), DRB1*13-DQB1*02 (P = 0.004), and DRB1*13-DQB1*03 (P = 3.79x10-8) were significantly associated with RA risk, while 3 protective haplotypes, DRB1*03-DQB1*02 (Pc = 0.008), DRB1*07-DQB1*02 (Pc = 0.004), and DRB1*13-DQB1*06 (Pc = 0.02) were identified. This is the first study determining the association between HLA class II alleles and haplotypes and RA risk in our population.

Studies concerning the genetic background of IgA vasculitis (IgAV), a small-vessel vasculitis occurring predominantly in childhood, have confirmed that the HLA-DRB1 gene showed a strong association with disease susceptibility. The objective was to investigate human leukocyte antigen (HLA) polymorphisms among Croatian patients with IgAV and their influence on disease susceptibility and clinical heterogeneity. Thus, 130 children with IgAV and 202 unrelated healthy individuals were enrolled in the study. Genomic DNA was extracted from whole peripheral blood, and HLA-A, -B, -DRB1 and -DQB1 gene polymorphism analysis was performed. HLA-A*03 (21.4% vs. 12.38%, p = 0.0092), HLA-B*37 (2.9% vs. 0.2%, p = 0.0054) and HLA-DRB1*12 (3.1% vs. 0.7%, p = 0.0216) alleles were significantly more frequent in IgAV patients than in controls. High-resolution typing revealed significantly higher frequency of HLA-DRB1*10:01 and -DRB1*11:03 among IgAV patients with gastrointestinal manifestations of the disease in comparison to controls (p = 0.0021 and p = 0.0301, respectively), while HLA-DRB1*14:01P occurred significantly more often in the group of patients who developed nephritis during the course of the disease (17.5% vs. 4.5%, p = 0.0006). Our results demonstrated that there is an association of HLA-A*03, HLA-B*37 and HLA-DRB1*12 alleles with susceptibility to IgAV in the examined Croatian pediatric population. Studies which aim to determine the HLA profile may contribute to the elucidation of the genetic background of autoimmune diseases, including IgAV.

The novel HLA‐DRB1*03:215 allele, first described in a potential bone marrow donor from Brazil. [ABSTRACT FROM AUTHOR]

Due to their pivotal role in orchestrating the immune response, HLA loci were recognized as candidates for genetic association studies related to the severity of COVID‐19. Since the findings on the effects of HLA alleles on the outcome of SARS‐CoV‐2 infection remain inconclusive, we aimed to elucidate the potential involvement of genetic variability within HLA loci in the molecular genetics of COVID‐19 by classifying the articles according to different disease severity/outcomes and by conducting a systematic review with meta‐analysis. Potentially eligible studies were identified by searching PubMed, Scopus and Web of Science literature databases. A total of 28 studies with 13,073 participants were included in qualitative synthesis, while the results of 19 studies with 10,551 SARS‐CoV‐2‐positive participants were pooled in the meta‐analysis. According to the results of quantitative data synthesis, association with COVID‐19 severity or with the lethal outcome was determined for the following alleles and allele families: HLA‐A*01, HLA‐A*03, HLA‐A*11, HLA‐A*23, HLA‐A*31, HLA‐A*68, HLA‐A*68:02, HLA‐B*07:02, HLA‐B*14, HLA‐B*15, HLA‐B*40:02, HLA‐B*51:01, HLA‐B*53, HLA‐B*54, HLA‐B*54:01, HLA‐C*04, HLA‐C*04:01, HLA‐C*06, HLA‐C*07:02, HLA‐DRB1*11, HLA‐DRB1*15, HLA‐DQB1*03 and HLA‐DQB1*06 (assuming either allelic or dominant genetic model). We conclude that alleles of HLA‐A, ‐B, ‐C, ‐DRB1 and ‐DQB1 loci may represent potential biomarkers of COVID‐19 severity and/or mortality, which needs to be confirmed in a larger set of studies. [ABSTRACT FROM AUTHOR]

Abstract Background Haplotypes defined by amino acids at HLA-DRB1 positions 11, 71 and 74 associated with susceptibility to rheumatoid arthritis (RA) are associated with radiological outcome, anti-TNF response and all cause-mortality in RA. RA is associated with cardiovascular (CV) morbidity and mortality, but the increased prevalence of risk factors of CV disease in RA only partially explains this association. The aim of this study was to investigate whether amino acids at positions 11, 71 and 74 of HLA-DRB1 are associated with cardiovascular (CV) mortality in inflammatory polyarthritis (IP). Methods The Norfolk Arthritis Register (NOAR) is an incidence register of IP: recruitment 1990–2007, final follow-up 2011. Two thousand five hundred fourteen patients had available genetic and mortality data. Amino acids at positions 11, 71 and 74 of HLA-DRB1 were determined. Univariate Cox proportional hazard models were applied to assess the association of genetic markers and both all-cause mortality and cardiovascular mortality. Results Among 2514 participants, 643 (25.6%) died during the study, and 343 (53.3%) of these deaths were attributed to CV causes. One thousand six hundred fifty (65.6%) participants were female, 709 (32.3%) were anti-CCP-positive and the median age of participants was 54. HLA-DRB1 haplotypes associated with susceptibility to rheumatoid arthritis (RA) consistently show the same magnitude and direction of association for overall and CV mortality in IP. For example, the SEA-haplotype, associated with the lowest susceptibility to RA, and the best radiographic outcome, was found to be associated with decreased CV mortality (HR 0.67, 95% CI 0.47, 0.91, p=0.023). Mediation analysis revealed associations were independent of anti-CCP status. Conclusions HLA-DRB1 haplotypes associated with susceptibility to RA also predispose to increased risk of CV mortality in IP, independent of known CV risk factors. Associations were independent of anti-CCP status, which suggests in the future, genetic factors will add to the prediction of risk of cardiovascular mortality beyond serological markers.

Abstract We explored the association between HLA‐B and HLA‐DRB1 polymorphisms and reviewed clinical characteristics of systemic lupus erythematosus (SLE) in Han population in Yunnan, China. Methods There were 295 patients and 265 healthy control subjects (HCs) enrolled in the study. Clinical data and blood samples were collected from the patients. The HLA‐B and HLA‐DRB1 genotypes were detected in SLE patients and HCs. Results A total of 74 genotypes on HLA‐B loci were determined in 288 patients as well as 57 genotypes in 265 HCs. The results showed SLE was associated with the HLA‐B*40:01 and HLA‐DRB1*08:03 alleles, and the HLA‐B*46:01, HLA‐DRB1*12:02, DRB1*04:03, DRB1*14:01, DRB1*04:06, and DRB1*11:01 alleles were less likely to appear in SLE patients. Additionally, HLA‐B*07:02 and B*40:06 were associated with disease activity. HLA‐DRB1*03:01, DRB1*13:02, and DRB1*12:01 were associated with proteinuria. Furthermore, HLA‐B*51:01, B*13:02, B*38:02, B*35:01, HLA‐DRB1*15:02, DRB1*15:04, DRB1*15:01, and DRB1*08:03 were correlated with inflammatory factors and immune dysfunction. HLA‐B*15:25 was related to the production of multiple antibodies. HLA‐DRB1*12:02 might be a protective factor for pancytopenia. The haplotype of HLA‐B*40:01/DRB1*08:03 was linked with SLE. Conclusion SLE in Han population in Yunnan province was associated with the HLA‐B*40:01 and HLA‐DRB1*08:03 alleles, and the haplotype HLA‐B*40:01/DRB1*08:03. Several alleles were associated with inflammation, immune disorders, and organ involvement in SLE. Those alleles might be potential genetic markers of SLE.

BackgroundThe genetic contributions to pediatric onset ulcerative colitis (UC), characterized by severe disease and extensive colonic involvement, are largely unknown. In adult onset UC, Genome Wide Association Study (GWAS) has identified numerous loci, most of which have a modest susceptibility risk (OR 0.84-1.14), with the exception of the human leukocyte antigen (HLA) region on Chromosome 6 (OR 3.59).MethodTo study the genetic contribution to exclusive pediatric onset UC, a GWAS was performed on 466 cases with 2099 healthy controls using UK Biobank array. SNP2HLA was used to impute classical HLA alleles and their corresponding amino acids, and the results are compared with adult onset UC.ResultsHLA explained the almost entire association signal, dominated with 191 single nucleotide polymorphisms (SNPs) (p = 5 x 10-8 to 5 x 10-10). Although very small effects, established SNPs in adult onset UC loci had similar direction and magnitude in pediatric onset UC. SNP2HLA imputation identified HLA-DRB1*0103 (odds ratio [OR] = 6.941, p = 1.92*10-13) as the most significant association for pediatric UC compared with adult onset UC (OR = 3.59). Further conditioning showed independent effects for HLA-DRB1*1301 (OR = 2.25, p = 7.92*10-9) and another SNP rs17188113 (OR = 0.48, p = 7.56*10-9). Two HLA-DRB1 causal alleles are shared with adult onset UC, while at least 2 signals are unique to pediatric UC. Subsequent stratified analyses indicated that HLA-DRB1*0103 has stronger association for extensive disease (E4: OR = 8.28, p = 4.66x10-10) and female gender (OR = 8.85, p = 4.82x10-13).ConclusionIn pediatric onset UC, the HLA explains almost the entire genetic associations. In addition, the HLA association is approximately twice as strong in pediatric UC compared with adults, due to a combination of novel and shared effects. We speculate the paramount importance of antigenic stimulation either by infectious or noninfectious stimuli as a causal event in pediatric UC onset.

Objective Systematic evaluation of the correlation of HLA-DQB1 and HLA-DRB1 allele polymorphisms with caries, to provide reference for caries prevention and treatment. Methods Relevant literature published before December 2020 was searched in the Cochrane Library, PubMed, Embase, Web of Science, Scopus, CNKI, Wanfang, VIP, and CBM databases. Meta-analysis was performed using the R4.0.2 software to test for heterogeneity and evaluate the publication bias. Results In total,10 case-control studies were included with 564 people in the case group and 676 people in the control group. The results of the Meta-analysis show that: ① HLA-DQB1*02 (OR=0.52, 95%CI=0.29-0.93, P < 0.05) and HLA-DRB1*09 (OR=0.34, 95%CI=0.21-0.58, P < 0.05) are protective factors of dental caries; ② HLA-DRB1*13 (OR=2.96, 95%CI=2.03-4.33, P < 0.05) and HLA-DRB1*14 (OR=1.95, 95%CI=1.26-3.02, P < 0.05) alleles are risk factors for the development of dental caries. The results of the subgroup analysis are: HLA-DRB1*07 is a caries susceptibility factor in the Chinese population (OR=0.48, 95% CI=0.24-0.97, P < 0.05), while it is not statistically significant in the Brazilian and Turkish populations; HLA-DRB1*11 is a caries protective factor in the saliva group (OR=2.26, 95% CI=1.46-3.52, P < 0.05). 3.52, P < 0.001), while it is a caries susceptibility factor in the blood group (OR=0.09, 95% CI=0.12-0.34, P < 0.001). Conclusion HLA-DRB1*13 and HLA-DRB1*14 alleles are caries susceptibility genes, and HLA-DQB1*02 and HLA-DRB1*09 have protective effects on the caries development. HLA-DRB1*07 is a caries susceptibility gene in the Chinese population; HLA-DRB1*11 is a caries protective gene in the saliva group. Due to the limited sample size and quality of the included studies, more high-quality studies will be included later for verification.

B cells, follicular helper T (Tfh) cells and follicular regulatory T (Tfr) cells are part of a circuit that may play a role in the development or progression of rheumatoid arthritis (RA). With the aim of providing further insight into this topic, here we evaluated the frequency of different subsets of Tfh and Tfr in untreated and long-term treated RA patients from a cohort of Argentina, and their potential association with particular human leukocyte antigen (HLA) class-II variants and disease activity. We observed that the frequency of total Tfh cells as well as of particular Tfh subsets and Tfr cells were increased in seropositive untreated RA patients. Interestingly, when analyzing paired samples, the frequency of Tfh cells was reduced in synovial fluid compared to peripheral blood, while Tfr cells levels were similar in both biological fluids. After treatment, a decrease in the CCR7loPD1hi Tfh subset and an increase in the frequency of Tfr cells was observed in blood. In comparison to healthy donors, seropositive patients with moderate and high disease activity exhibited higher frequency of Tfh cells while seropositive patients with low disease activity presented higher Tfr cell frequency. Finally, we observed that HLA-DRB1*09 presence correlated with higher frequency of Tfh and Tfr cells, while HLA-DRB1*04 was associated with increased Tfr cell frequency. Together, our results increase our knowledge about the dynamics of Tfh and Tfr cell subsets in RA, showing that this is altered after treatment.

Genome-wide association studies (GWAS) of Alzheimer's disease (AD) have identified a large number of susceptibility genes, but most of AD heritability remains unexplained, implying the existence of additional genes. Furthermore, the majority of the GWAS have been conducted in people of European descent, and the genes important for AD susceptibility in people of African descent have been underexplored. In this hypothesis-generating prospective cohort study, we genotyped 191 African Americans (AAs) from three longitudinal cohorts on aging for the IgG3 allotype GM6, which is expressed exclusively in people of African descent, and assessed its interaction with IGHG, FCGRIIB, and HLA-DRB1 genes. Cox proportional hazards modeling showed that GM6 by itself was not significantly associated with AD development. However, there was evidence of epistatic interaction: The risk of developing AD associated with GM6 positivity was significantly different (p = 0.0098) in non-GM17/GM17 participants compared with GM 17/GM17 participants. Specifically, in non-GM17/GM17 participants, the risk of AD was over fourfold higher in GM6-positive participants compared with GM 6-negative participants (HR = 4.63). Similarly, risk of developing AD associated with GM6 positivity was marginally different in non-FCGRIIB TT participants compared with FCGRIIB TT participants. In non-FCGRIIB TT participants, the risk of developing AD was over twofold higher in GM6-positive participants compared with GM6-negative participants (HR = 2.44). This is the first report suggesting that immunoglobulin GM allotypes might play a role in AD etiology among AAs; however, since this was largely a hypothesis-generating study, replication in larger cohorts would be required to confirm this finding., (© 2024. The Author(s).)

Background: Genetics influence the clinical picture in sarcoidosis, a granulomatous heterogeneous disease often accompanied by elevated serum angiotensin converting enzyme (s-ACE). We aimed to investigate if certain HLA-DRB1 alleles correlate with the levels of s-ACE, known as a marker of the granuloma burden., Methods: Medical journals of patients with sarcoidosis from a Swedish clinical registry were retrospectively examined to extract the highest recorded s-ACE value and analysed in relation to patient characteristics including phenotype [Löfgren syndrome (LS)/ non-LS], chest X-ray staging according to Scadding, treatment with immunosuppressants, presence of extrapulmonary manifestations (EPM), HLA-DRB1 alleles and prognosis (resolving vs. non-resolving disease within 2 years). Data were analysed with Fisher's exact test and Bonferroni correction was applied for HLA analyses., Results: Of 1204 patients included, 40% had s-ACE levels above reference value. In comparison with patients with normal s-ACE, those with elevated levels were more often classified into non-LS (78% vs 59%, p < 0.001), and Scadding stage II (50% vs 38%, p < 0.001) but less often Scadding stage I (33% vs 46%, p < 0.001) and had more often EPM (45% vs 23%, p < 0.001). The patients with HLA-DRB1×04 had more often elevated s-ACE (p < 0.01) while those with HLA-DRB1×03 commonly had normal levels (p < 0.001)., Conclusions: In this retrospective study, HLA alleles associated with s-ACE levels in sarcoidosis patients, which in turn correlated with occurrence of EPM. These findings shed some new light on possible mechanisms behind differences in s-ACE levels., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Masson SAS.)

Abstract Objective Cervical cancer is a gynecological health problem, affecting nearly 500,000 women each year worldwide. Genome‐wide association studies have revealed multiple susceptible genes and their polymorphisms for cervical carcinoma risk. We have carried out this case‐control study to investigate the association of INSIG2 rs6726538 (A; T), HLA‐DRB1 rs9272143 (T; C), and GCNT1P5 rs7780883 (G; A) with cervical cancer. Methods The present study recruited 234 cervical cancer patients as cases and 212 healthy females as controls. We have applied the tetra‐primer amplification refractory mutation system polymerase chain reaction (T‐ARMS‐PCR) method for genotyping. Results The SNP rs6726538 was significantly associated with increased risk of cervical cancer in all genetic models (AT vs. AA: OR = 3.30, 95% CI = 2.19–4.97, p

Congenital heart defects are anomalies that are becoming more and more frequent every year. Their specific weight is the highest among all the defects and malformations in fetus. Besides, children with sporadic congenital heart defects and malformations are still born rather frequently. We made an assumption that congenital heart defects (CHD) and congenital malformations (CM) were formed due to inflammatory process decompensation within «mother – fetus» system occurring in case of a conflict as per HLA between a semi-allogenic fetus and its mother’s microenvironment. A risk of such a conflict might be associated with certain HLA combinations in parents’ genotypes. Our research goal was to reveal peculiarities of HLA-DRB1 alleles combinations in married couples who had children with sporadic CHD and CM without any chromosome diseases and to determine whether such peculiarities could cause risks of congenital anomalies. We determined frequency of 14 alleles in HLA-DRB1 gene in all people who took part in the research. Our research allowed establishing that parents whose children suffered from CHD more frequently had common HLA-DRB104, female HLA-DRB107 with male HLA-DRB113, HLA-DRB117 and female HLA-DRB113 with male HLA-DRB114. Children who suffered from CM more frequently had parents who were homologous as per HLA-DRB112, as well as with female HLA-DRB112 and male HLA-DRB101, HLA-DRB104, HLA-DRB113, and HLA-DRB115; this greater frequency was statistically significant. We also detected an authentic increase in frequency of HLA-DRB112 allele in children against their parents. Children with CM also had HLA-DRB112 allele statistically significantly more frequently than healthy children. Peculiarities related to HLA-DRB1 alleles combination are genetic predictors of CHD and CM occurrence; their determination will allow minimizing risks of such disorders due to early diagnostics and timely prevention.

Pemphigus is a group of rare, lifethreatening bullous autoimmune diseases that affect the skin and mucous membranes and are associated with high morbidity and morbidity. HLA class II genes, particularly HLA-DRB1 and HLA-DQB1, play roles in pemphigus. The aim of this paper is to investigate the susceptibility of HLA class II DRB1 and DQB1 alleles in Vietnamese patients with pemphigus vulgaris (PV) or pemphigus foliaceus (PF). The study enrolled 31 participants (22 with PV, 9 with PF) with diagnoses confirmed by clinical manifestations, histopathology, and direct immunofluorescence from November 2019 to June 2020. The HLA polymorphisms were determined by Sanger sequencing. The HLA-DRB1 and HLA-DQB1 profiles of the 101 healthy individuals in the control group have been published previously. The frequencies of HLA-DRB1*14, DRB1*13:07, DRB1*04:04, DRB1*03:02, DQB1*02:02, and DQB1*05:03 were significantly higher, whereas those of DRB1*09:01, DRB1*12:02, DQB1*03:03, DQB1*05:01, and DQB1*06:01 were significantly lower, in the PV group than in the controls. The frequencies of DRB1*14:54, DRB1*13:07, and HLA-DQB1*03:02 were significantly higher in the PF group than in the controls. Alleles HLA-DRB1*14:54, DRB1*14:04, DRB1*14:03, DRB1*14:01, DRB1*14:12, DRB1*13:07, DRB1*04:04, DRB1*03:02, DQB1*02:02, and DQB1*05:03 were associated with an increased risk of PV, whereas alleles DRB1*09:01, DRB1*12:02, DQB1*03:03, DQB1*05:01, and DQB1*06:01 might protect against PV. In PF, DRB1*14:54, DRB1*13:07, and HLA-DQB1*03:02 are promising susceptibility alleles. [ABSTRACT FROM AUTHOR]

Background: Vitiligo is a multifactorial depigmentation condition, which is due to skin melanocyte destruction. Increased expression of HLA class II genes in patients with pre-lesions of Vitiligo suggests a crucial role for the participation of immune response in Vitiligo development. Recent studies progressively focused on HLA-DRB1 and DQB1 genes. In this study, we have evaluated the association and role of HLA-DRB4*01:01, -DRB1*07:01, and -DQB1*03:03:2 genes in different clinical subtypes of Vitiligo in the Iranian population. Methods: First, Genomic DNA from peripheral blood of 125 unrelated Vitiligo patients and 100 unrelated healthy controls were extracted through the salting-out method. Then, HLA class II genotyping was performed using the sequence-specific primer PCR method. Finally, the clinical relevance of the testing for these genotypes was evaluated by applying the PcPPV (prevalence-corrected positive predictive value) formula. Results: Our results indicated the positive associations of DRB4*01:01 and DRB1*07:01 allelic genes with early-onset Vitiligo (p = 0.024 and 0.022, respectively). DRB4*01:01 also showed strong protection against late-onset Vitiligo (p = 0.0016, RR = 0.360). Moreover, our data revealed that the DRB1*07:01 increases the susceptibility to Sporadic Vitiligo (p = 0.030, RR = 1.702). Furthermore, our findings proposed that elevated vulnerability of Vitiligo patients due to DRB4*01:01 and DRB1*07:01 alleles maybe is correlated with the presence of amino acid Arginine at position 71 at pocket 4 on the antigen-binding site of the HLA-DRB1 receptor. Conclusion: Our findings on different subtypes of Vitiligo suggest that, despite a more apparent autoimmune involvement, a non-autoimmune nature for the etiology of Vitiligo should also be considered. [ABSTRACT FROM AUTHOR]

Abstract Background Ovarian teratoma-associated anti-N-methyl-D-aspartate receptor encephalitis (NMDAR-E) is a severe autoimmune neurological disorder, and the influence of teratoma-induced autoantibodies on the pathogenesis remains unclear. Methods Ovarian teratoma tissues were collected from teratoma patients with and without NMDAR-E. Proteins were extracted and then analyzed using iTRAQ-coupled LC–MS/MS, which was followed by bioinformatics analysis. Candidate proteins were verified by Western blotting and immunohistochemistry. Results In total, 36 differentially expressed proteins (DEPs) were identified between the control group and NMDAR-E group, and the bioinformatics analysis revealed that the DEPs were mainly involved in immune-related pathways, especially HLA-A and HLA-DRB1. The western blotting results for HLA-A and HLA-DRB1 were consistent with the results of the iTRAQ analysis. Additionally, the immunohistochemical data revealed that the aggregation of HLA-A (+) and HLA-DRB1 (+) cells was more apparent in the teratoma tissues of NMDAR-E patients compared with that in the tissues of controls. Conclusion Our investigation indicated that HLA-A and HLA-DRB1 might be involved in mediating ovarian teratoma-associated NMDAR-E. These findings provide new insights into the pathophysiological mechanisms and provide information for the functional exploration of proteins in the future.

Recent systematic reviews and a meta-analysis have shown that there is insufficient evidence on the relationship of multiple sclerosis (MS) to vitamin D supplementationObjective: to assess the relationship of vitamin D status in MS patients to insolation, disease course, and HLA-DRB1 gene polymorphism. Patients and methods. The one-stage study enrolled 90 patients with relapsing-remitting MS (a study group) and 87 volunteers without this disease (a control group). The enrolled were born and live in the Altai Territory of the Russian Federation. The serum level of 25(OH)D was measured by enzyme immunoassay.Results and discussion. 25(OH)D

Gland and Hormonal Diseases (GHDs) constitute a class of non-communicable diseases that primarily results from either excessive or reduced secretion of hormones. Many of these diseases also have neurological manifestations. The need for their molecular understanding and subsequent effective drug target identification is paramount. Here, we have constructed Protein-Protein Interactions (PPI) networks by integrating intricate genomic and proteomic data available on various GHDs. From the network, hub proteins, key pathways, and gene ontologies were derived. The members of this network were then investigated for unraveling strong association with neurological disorders and a network of neurological disorder-associated genes was also constructed. Functional clusters in both the GHDs and neurological disorders were analyzed and compared. Based on our analyses, we have identified CBS, GJB2, KCNJ10, ERCC6, IGF1, HFE, GJB2, SOX2, SOX4, NTRK1, SOX9, BRCA1 and ERCC4 as common players in GHDs and neurological disorders. Hub proteins of GHDs include IGF1, TGFB1, JUN, and SMAD3 and those of neurological disorders include INS and IL6. These proteins could be considered as potential biomarkers. Our analysis suggest that perturbations in DNA damage repair, glucocorticoid hormone metabolism, interferon gamma mediated signaling pathway, and immune system regulation might promote GHDs while oxidative stress can do the same for neurological disorders. TGFB1 and SMAD3 agonists possess therapeutics potential against Alzheimer's disease. HLA-DRB1, HLA-DQB1 and TNF might have special role in either type of diseases. This study will pave the way for identification of biomarkers, drug targets and provide explanations regarding molecular and immunological pathogenesis in GHD-induced neurological disorders.

The novel HLA‐DRB1*16:01:19 allele differs by one nucleotide change from HLA‐DRB1*16:01:01. [ABSTRACT FROM AUTHOR]

The novel HLA‐DRB1*13:342 allele was characterized using next generation sequencing technology. [ABSTRACT FROM AUTHOR]

The novel HLA‐DQB1*05:323 allele was characterized using next generation sequencing technology. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV) infection is a necessary cause for cervical cancer (CC), but it also depends on genetic factors, such as HLA polymorphism. However, few reports addressed the role of amino acids residues at the HLA peptide‐binding cleft in HPV‐related cervical disease. Therefore, we aimed to investigate the association between HLA‐B, HLA‐C, and HLA‐DRB1 polymorphism and amino acid residues composing the pockets of the peptide‐binding cleft of the respective polypeptide chains with cervical intraepithelial neoplasia (CIN II/III). HLA typing was performed by PCR‐SSOP in 184 women with CIN II/III and 174 controls from South Brazil. Associations were estimated by multivariate logistic regression. FDR test was performed to correct the p‐value for multiple comparisons. HLA‐DRB1*13:01 was associated with protection against CIN II/III, while HLA‐C*03:04 was associated with susceptibility. The amino acid residues isoleucine, tyrosine, and leucine at positions 95, 116, and 163 of HLA‐C, respectively, were associated with CIN II/III susceptibility. In contrast, serine at positions 11 and 13 of HLA‐DRB1 was associated with protection against the disease. Our results confirm previously reported associations between HLA and cervical diseases caused by HPV and suggest a role for amino acid residues at different positions of HLA‐C and HLA‐DRB1 in CIN II/III. This finding may be further explored to better understand the genetic risk and the influence of immune response to CC development. [ABSTRACT FROM AUTHOR]

Human leukocyte antigen (HLA) genes with extreme diversity can make a contribution for individual variations to the immune response against SARS-COV-2 infection. This study aimed to explore the distributions of HLA class II alleles frequencies and their relations with disease severity in a group of Iranian COVID-19 patients. This prospective and case-control study was conducted on 144 COVID-19 patients including 46 cases with moderate form, 54 cases with severe and 44 cases with critical disease. HLA-DRB1 and -DQB1 allele families were determined by PCR-SSP method and compared between three groups of the patients and in comparison to 153 ethnic-matched healthy controls. The patients group showed lower frequencies of HLA-DRB1*15 (OR = 0.57, P = 0.06), DRB1*15 ~ DQB1*05 haplotype (P = 0.04) and DRB1*15/DRB1*04 genotype (P = 0.04) in compare with healthy controls. Moderate COVID-19 patients had higher frequencies of HLA-DRB1*04 (P = 0.03), HLA-DRB1*10 (P = 0.05) and DRB1*04/DRB1*11 genotype (P = 0.01). Also, a higher significantly frequency of HLA-DRB1*03 allele group was observed in the critical patients versus controls (P = 0.01). Multiple logistic regression analysis revealed that the presence of DRB1*04 allele group was negatively associated with development of severe and critical disease (OR: 0.289, P = 0.005). Our results indicate a possible contribution of some HLA class II alleles in disease severity and clinical features of COVID-19 disease. [ABSTRACT FROM AUTHOR]

• HLA genes are the most relevant genetic component for SLE disease risk and autoantibodies formation. • DRB1*03 allele was significantly associated with anti-SSA and anti-SSB antibodies production. • DRB1*16 genotypes either homozygote or heterozygote were positively associated with ANA and anti-Sm. • Dominant role of DRB1 over DQB1 alleles was observed for disease predisposition. One 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. A 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. We found that HLA-DRB1*03 and HLA-DRB1*16 alleles were significantly associated with increased risk (P = 0.008, P C =0.05 and P = 0.002, P C =0.02 respectively) and DRB1*01 conferred a potential protective role for disease (P = 0.03, P C =0.13). Similar associations were observed at haplotype level; DRB1*03~DQB1*02 (OR1.91, P = 0.01, P C =0.08), DRB1*16~DQB1*05 (OR3.65, P = 0.004,P C =0.06) and DRB1*01~DQB1*05 (OR0.36, P = 0.04, P C =0.22). Remarkably, we observed significantly associations of DRB1*03 with the appearance of anti-SSA/Ro (P C =0.02), anti-SSB/La (P C =0.002) and anti-coagulant (P = 0.007), DRB1*15 with anti-SSA/Ro (P C =0.04), DRB1*16 with anti-Sm (P C =0.02), DRB1*04 with anti-β2gpI (P C =3 * 10−5), anti-cardiolipin (P = 0.002) and rheumatoid factor (P = 0.004) and DRB1*13 with anti-Sm (P C =0.02) and anti-β2gpI (P C =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. We 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. [ABSTRACT FROM AUTHOR]

The analysis of polymorphic variations in the human major histocompatibility complex (MHC) class II genomic region on the short-arm of chromosome 6 is a scientific enquiry to better understand the diversity in population structure and the effects of evolutionary processes such as recombination, mutation, genetic drift, demographic history, and natural selection. In order to investigate associations between the polymorphisms of HLA-DRB1 gene and recent Alu insertions (POALINs) in the HLA class II region, we genotyped HLA-DRB1 and five Alu loci (AluDPB2, AluDQA2, AluDQA1, AluDRB1, AluORF10), and determined their allele frequencies and haplotypic associations in 12 minority ethnic populations in China. There were 42 different HLA-DRB1 alleles for ethnic Chinese ranging from 12 alleles in the Jinuo to 28 in the Yugur with only DRB1∗08:03, DRB1∗09:01, DRB1∗12:02, DRB1∗14:01, DRB1∗15:01, and DRB1∗15:02 present in all ethnic groups. The POALINs varied in frequency between 0.279 and 0.514 for AluDPB2, 0 and 0.127 for AluDQA2, 0.777 and 0.995 for AluDQA1, 0.1 and 0.455 for AluDRB1 and 0.084 and 0.368 for AluORF10. By comparing the data of the five-loci POALIN in 13 Chinese ethnic populations (including Han-Yunnan published data) against Japanese and Caucasian published data, marked differences were observed between the populations at the allelic or haplotypic levels. Five POALIN loci were in significant linkage disequilibrium with HLA-DRB1 in different populations and AluDQA1 had the highest percentage association with most of the HLA-DRB1 alleles, whereas the nearby AluDRB1 indel was strongly haplotypic for only DRB1∗01, DRB1∗10, DRB1∗15 and DRB1∗16. There were 30 five-locus POALIN haplotypes inferred in all populations with H5 (no Alu insertions except for AluDQA1) and H21 (only AluDPB2 and AluDQA1 insertions) as the two predominant haplotypes. Neighbor joining trees and principal component analyses of the Alu and HLA-DRB1 polymorphisms showed that genetic diversity of these genomic markers is associated strongly with the population characteristics of language family, migration and sociality. This comparative study of HLA-DRB1 alleles and multilocus, lineage POALIN frequencies of Chinese ethnic populations confirmed that POALINs whether investigated alone or together with the HLA class II alleles are informative genetic and evolutionary markers for the identification of allele and haplotype lineages and genetic variations within the same and/or different populations.

ObjectivesRheumatoid arthritis (RA) is associated with HLA-DRB1 genes encoding the shared epitope (SE), a 5-amino acid motive. RA is usually preceded by the emergence of anti-citrullinated protein/peptide antibodies (ACPAs). Citrulline is a neutral amino acid resulting from post-translational modification of arginine involved in peptidic bounds (arginyl residue) by PeptidylArginine Deiminases (PADs). ACPAs recognize epitopes from citrullinated human fibrin(ogen) (hFib) and can be specifically detected by the AhFibA assay. Five citrullinated peptides derived from hFib together represent almost all of the epitopes recognized by patients with ACPA-positive RA, namely: α36–50cit, α171–185cit, α501–515cit, α621–635cit, and β60–74cit. The use of antibody fine specificities as markers of clinical phenotypes has become a major challenge. Our objective was to study whether RA clinical characteristics and HLA-DRB1 genetic background were associated with a specific reactivity against the epitopes borne by the five peptides.Methods184 ACPA-positive RA patients fulfilling the 2010 ACR/EULAR criteria were studied. Patient characteristics including HLA-DRB1 genotype, were collected from their medical files. Anti-CCP2 antibodies, AhFibA, and antibodies against the five citrullinated hFib (hFib-cit) peptides were analyzed by ELISA.ResultsAnti-α505-515cit antibodies were associated with HLA-DRB1*04:01 (OR = 5.52 [2.00 – 13.64]; p = 0.0003). High level anti-α505-515cit antibodies were associated with rheumatoid nodules (OR = 2.71 [1.00 – 7.16], p= 0.044).ConclusionImmune complexes containing anti-α501-515cit antibodies and rheumatoid factors might be involved in the development of rheumatoid nodules on the HLA-DRB1*04:01 background. Apheresis of these epitope-specific antibodies might be a new therapeutic opportunity for patients with rheumatoid nodules.