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Background: The fibrosis-4 (FIB-4) index is a non-invasive method to assess the severity of liver fibrosis. The development of liver fibrosis is influenced by genetic predisposition and dietary factors. However, the modulating effect of dietary factors on the genetic susceptibility of liver fibrosis remains unclear. The study aims to investigate the role of dietary factors in modulating the genetic susceptibility of liver fibrosis. Methods: Here, we conducted a genome-wide association study (GWAS) of FIB-4 index-directed liver fibrosis risk, adjusted with diet, lifestyle factors, and hepatitis serological markers. The high (N = 1,476) and low (N = 36,735) liver fibrosis risk groups were defined with a FIB-4 > 2.67 and < 1.3, respectively. Results: The age-related FIB-4 variation showed subjects with a FIB-4 > 2.67 (3.8%), indicating high fibrosis risk, occurred predominantly among individuals above 60 years old. The multivariable analysis showed that tea intake is significantly associated with a reduced risk of liver fibrosis. The GWAS adjusted for sex, age, age2, dietary factors (tea and coffee consumption, vegetarian preference), lifestyle (alcohol consumption, physical activity), hepatitis serological markers (anti-HCV, HBsAg, HBeAg), and the top ten principal components indicated 25 genome-wide significant signals (p < 5 × 10− 8). Two variants (rs56293029 and rs9389269) were previously associated with the FIB-4 index in alcohol-related cirrhosis, while the 23 SNPs remaining were novel. The rs9399136 (HBS1L) is a protective variant, and rs9274407 (HLA-DQB1) is a risk variant, both contributing to liver fibrosis development. Our results showed that genetic factors play a major role in liver fibrosis, while dietary factors have minor effects on disease progression. Pathway analysis suggested the potential of immune response and hematopoietic systems function in the pathogenesis of liver disease. Conclusions: The studies not only revealed the protective role of rs9399136 (HBS1L) and the risk effect of rs9274407 (HLA-DQB1) toward liver fibrosis in a Taiwanese population, but also demonstrated that individual consumption patterns, such as tea uptake, have a minor impact on liver fibrosis prevention. The pathway analysis from GWAS variants further indicated the importance of immune responses in the pathogenesis of liver fibrosis. [ABSTRACT FROM AUTHOR]

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]

Abstract Background The fibrosis-4 (FIB-4) index is a non-invasive method to assess the severity of liver fibrosis. The development of liver fibrosis is influenced by genetic predisposition and dietary factors. However, the modulating effect of dietary factors on the genetic susceptibility of liver fibrosis remains unclear. The study aims to investigate the role of dietary factors in modulating the genetic susceptibility of liver fibrosis. Methods Here, we conducted a genome-wide association study (GWAS) of FIB-4 index-directed liver fibrosis risk, adjusted with diet, lifestyle factors, and hepatitis serological markers. The high (N = 1,476) and low (N = 36,735) liver fibrosis risk groups were defined with a FIB-4 > 2.67 and 2.67 (3.8%), indicating high fibrosis risk, occurred predominantly among individuals above 60 years old. The multivariable analysis showed that tea intake is significantly associated with a reduced risk of liver fibrosis. The GWAS adjusted for sex, age, age2, dietary factors (tea and coffee consumption, vegetarian preference), lifestyle (alcohol consumption, physical activity), hepatitis serological markers (anti-HCV, HBsAg, HBeAg), and the top ten principal components indicated 25 genome-wide significant signals (p

Identification of seven new HLA alleles by next‐generation sequencing. [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. [ABSTRACT FROM AUTHOR]

HLA‐DQB1*06:432 differs from HLA‐DQB1*06:09:01:01 by a nonsynonymous nucleotide substitution in codon 186, changing Valine to Methionine. [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]

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.

The novel HLA‐DQB1*06:02:62 allele, first described in an individual from Brazil. [ABSTRACT FROM AUTHOR]

The novel allele, HLA‐DQB1*03:517, differs by a single nucleotide substitution in exon 3 to HLA‐DQB1*03:02:01:02. [ABSTRACT FROM AUTHOR]

The novel HLA‐DQB1*03:01:61 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]

Soetjipto,1,2,&ast; Nur Rochmah,2,3,&ast; Muhammad Faizi,2,3 Yuni Hisbiyah,2,3 Anang Endaryanto2,3 1Department of Medical Biochemistry, Faculty of Medicine, Universitas Airlangga, Surabaya, East Java, Indonesia; 2Doctoral Program of Medical Science, Faculty of Medicine, Universitas Airlangga, Surabaya, East Java, Indonesia; 3Faculty of Medicine, Department of Child Health, Dr. Soetomo General Hospital, Universitas Airlangga, Surabaya, East Java, Indonesia&ast;These authors contributed equally to this workCorrespondence: SoetjiptoDoctoral Program of Medical Science, Faculty of Medicine, Universitas Airlangga, Mayjend Prof. Dr. Moestopo No. 6-8, Surabaya, East Java, 60286, IndonesiaEmail Soetjipto1950@gmail.comBackground: More than 40 genes influence the progression of type 1 diabetes mellitus (T1DM), including human leukocyte antigen (HLA) alleles. Different HLA genotype patterns result in diverse rates of T1DM development. HLA class II DR, DQ, and DP vary among different populations and ethnicities. Data on HLA polymorphism in T1DM in Indonesia are lacking. Therefore, this study was designed to evaluate the gene polymorphism of HLA-DQA1 and HLA-DQB1 in Indonesian children with T1DM.Patients and Methods: In this study, 31 patients with T1DM and 31 controls were enrolled from April 2020 to April 2021. This study was conducted at Dr. Soetomo Hospital, Indonesia. We evaluated the gene polymorphism of HLA-DQA1 and HLA-DQB1 using polymerase chain reaction–restriction fragment length polymorphism. The primers used were as follows: for HLA-DQA1, DQAS34: 5ʹ-GGTGTAAACTTGTACCAG-3ʹ (forward) and DQAA261: 5ʹ-ATTGGTAGCAGCGGTAGA-3ʹ (reverse); for HLA-DQB1, DQBS43: 5ʹ-TGCTACT- TCACCAA(C/T)GGG-3ʹ (forward) and DQBA249: 5ʹ-GTAGTTGTGTCTGCA (C/T)AC-3ʹ (reverse).Results: The most common HLA-DQA1 subtype in the T1DM group was 0101/0102 accounting for 67.6%, and 01/03 and 02/03 were found in the T1DM group only. Meanwhile, the most common HLA-DQB1 subtype in the T1DM group was 0301, accounting for 54.8%. Most subjects in this study were Javanese.Conclusion: HLA-DQA1 0101/0102 and HLA-DQB1 0301 were commonly found in Indonesian children with T1DM.Keywords: T1DM, HLA-DQA1, HLA-DQB1, gene polymorphism

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.

Characterization of new alleles, three HLA‐DQA1 and one HLA‐DQB1, bearing non‐synonymous and synonymous mutations, respectively. [ABSTRACT FROM AUTHOR]

Narcolepsy is a chronic neurological and a genetic disorder of autoimmune origin, which is characterized by five main symptoms, including excessive day time sleepiness, sudden loss of muscle tone or cataplexy, sleep paralysis, hypnagogic hallucinations, and disturbed nocturnal sleep. While there are several diagnostic tests for Narcolepsy such as MSLT (mean sleep latency test), polysomnography and low range of hypocretin in cerebrospinal fluid (CSF), sensitivity and specificity in these methodologies are not sufficient enough. Therefore, methods with higher sensitivity for the accurate diagnosis and confirmation of the disease are necessary. According to the infrequent prevalence of narcolepsy disease, we scheduled a case-control association study with 20 narcoleptic patients and 150 healthy individuals in a high-resolution HLA typing procedure employing SSP-PCR. Our study demonstrates that the DQB1*06:02 allele provides the highest susceptibility with absolute risk of 0.13%, for Narcolepsy (P = 1x10−14, RR = 60.5, PcPPV = 0.13%), while, HLA-DQB1* 03:05 allele presents protection to Narcolepsy (P = 1x10−4, PcPPV = 3.19x10−4%). Furthermore, for the first time, the AA analysis displayed that AA serine182 and threonine185 located on epitope of DQβ1 chain receptor (DQB1Ser182,Thr185) present significant susceptibility for Narcolepsy (Pc= 87.03 × 10−13, PcPPV = 0.024%) while, asparagine182 located on epitope of DQβ1 protein receptor (DQB1Asn182) confers the highest protection against development of Narcolepsy (Pc= 2.16 × 10−5, PcPPV = 0.0012%). Thus, this can be proposed that the polymorphic differences in the epitope of the HLA receptor could contribute to their differential association with the Narcolepsy in Iranian population. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) affects more than 1% of children, and there is no viable pharmacotherapeutic agent to treat the core symptoms of ASD. Studies have shown that children with ASD show changes in their levels of immune response molecules. Our previous studies have shown that ASD is more common in children with folate receptor autoantibodies. We also found that children with ASD have abnormal gut immune function, which was characterized by a significant increase in the content of immunoglobulin A and an increase in gut-microbiota-associated epitope diversity. These studies suggest that the immune mechanism plays an important role in the occurrence of ASD. The present study aims to systematically assess gene mutations in immune mediators in patients with ASD. We collected genetic samples from 72 children with ASD (2–12 years old) and 107 healthy controls without ASD (20–78 years old). We used our previously-designed immune gene panel, which can capture cytokine and receptor genes, the coding regions of MHC genes, and genes of innate immunity. Target region sequencing (500×) and bioinformatics analytical methods were used to identify variants in immune response genes associated with patients with ASD. A total of 4 rare variants were found to be associated with ASD, including HLA-B: p.A93G, HLA-DQB1: p.S229N, LILRB2: p.R322H, and LILRB2: c.956-4C>T. These variants were present in 44.44% (32/72) of the ASD patients and were detected in 3.74% (4/107) of the healthy controls. We expect these genetic variants will serve as new targets for the clinical genetic assessment of ASD, and our findings suggest that immune abnormalities in children with ASD may have a genetic basis. [ABSTRACT FROM AUTHOR]

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

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]

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

ObjectiveTo evaluate the association between single-nucleotide polymorphisms (SNPs) in RNA-seq identified mRNAs and silicosis susceptibility.MethodsA comprehensive RNA-seq was performed to screen for differently expressed mRNAs in the peripheral blood lymphocytes of eight subjects exposed to silica dust (four silicosis cases and four healthy controls). Following this, the SNPs located on the shortlisted mRNAs, which may affect silicosis susceptibility, were screened through silicosis-related genome-wide association studies (GWAS) (155 silicosis cases and 141 healthy controls), whereas functional expression quantitative trait locus (eQTL)-SNPs were identified using the GTEx database. Finally, the association between functional eQTL-SNPs and silicosis susceptibility (194 silicosis cases and 235 healthy controls) was validated.ResultsA total of 70 differentially expressed mRNAs (fold change > 2 or fold change < 0.5, P < 0.05) was obtained using RNA-seq. Furthermore, 476 SNPs located on the shortlisted mRNAs, which may affect silicosis susceptibility (P < 0.05) were obtained using GWAS, whereas subsequent six functional eQTL-SNPs were identified. The mutant A allele of rs9273410 in HLA-DQB1 indicated a potential increase in silicosis susceptibility in the validation stage (additive model: odds ratio (OR)= 1.31, 95% confidence interval (CI) = 0.99–1.74, P = 0.061), whereas the combination of GWAS and the validation results indicated that the mutant A allele of rs9273410 was associated with increased silicosis susceptibility (additive model: OR = 1.35, 95% CI =1.09–1.68, P = 0.006).ConclusionThe mutant A allele of rs9273410 was associated with increased silicosis susceptibility by modulating the expression of HLA-DQB1.

HLA‐DQB1*06:465 differs from HLA‐DQB1*06:04:01:01 by a non‐synonymous nucleotide substitution in codon 38. [ABSTRACT FROM AUTHOR]

The sequence of HLA‐DQB1*04:01:01:04 differs from HLA‐DQB1*04:01:01:03 by four nucleotide deletion in intron 2. [ABSTRACT FROM AUTHOR]

One nucleotide substitution in codon 152 of HLA‐DQB1*06:03:01:01 results in a novel allele, HLA‐DQB1*06:474. [ABSTRACT FROM AUTHOR]

Identification of the novel HLA‐DQB1*04:72 allele that differs from DQB1*04:02:01:06 by two nucleotide substitutions. [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]

Severe bleeding is a major cause of death in acute leukemia (AL) patients with graft-versus-host disease (GVHD) after allogene hematopoietic stem-cell transplantation (allo-HSCT). However, the prognostic value and prediction of HSCT-associated severe bleeding in GVHD patients have not been reported in cohort studies. We did a retrospective analysis of 200 AL patients with GVHD after allo-HSCT from Feb 1, 2014, to Dec 1, 2015. Multivariate analysis showed that the severe bleeding class was associated with the risk of death (HR 2.26, 95% CI 1.31–3.92, p<0.001***). In order to predict severe bleeding and figure out the solution to bleeding events, we established a multiple logistic regression model. HLA-DQB1 unmatching, megakaryocyte reconsititution failure, and III or IV GVHD were the independent risk factors for severe bleeding. Among all the variations above, OR of HLA-DQB1 was the highest (OR: 16.02, 95% CI: 11.54–48.68). Adding HLA-DQB1 to other factors improved the reclassification for predicting severe bleeding (NRI=0.195, z=2.634, p=0.008**; IDI=0.289, z=3.249, p<0.001***). Lasso regression was used to select variants. A nomogram of the logistic model was generated and displayed. Calibration curve demonstrated excellent accuracy in estimating severe bleeding (C index of 0.935). HLA-DQB1 showed excellent efficacy of predicting severe bleeding in HSCT patients. [ABSTRACT FROM AUTHOR]

Background: We took advantage of the 2015-2016 Brazilian arbovirus outbreak (Zika [ZIKV]/dengue/chikungunya viruses) associated with neurological complications to type HLA-DRB1/DQA1/DQB1 variants in patients exhibiting neurological complications and in bone marrow donors from the same endemic geographical region.Methods: DRB1/DQA1/DQB1 loci were typed using sequence-specific oligonucleotides. In silico studies were performed using X-ray resolved dimer constructions.Results: The DQA1*01, DQA1*05, DQB1*02, or DQB1*06 genotypes/haplotypes and DQA1/DQB1 haplotypes that encode the putative DQA1/DQB1 dimers were overrepresented in the whole group of patients and in patients exhibiting peripheral neurological spectrum disorders (PSD) or encephalitis spectrum disorders (ESD). The DRB1*04, DRB1*13, and DQA1*03 allele groups protected against arbovirus neurological manifestation, being underrepresented in whole group of patients and ESD and PSD groups. Genetic and in silico studies revealed that DQA1/DQB1 dimers (1) were primarily associated with susceptibility to arbovirus infections; (2) can bind to a broad range of ZIKV peptides (235 of 1878 peptides, primarily prM and NS2A); and (3) exhibited hydrophilic and highly positively charged grooves when compared to the DRA1/DRB1 cleft. The protective dimer (DRA1/DRB1*04) bound a limited number of ZIKV peptides (40 of 1878 peptides, primarily prM).Conclusion: Protective haplotypes may recognize arbovirus peptides more specifically than susceptible haplotypes. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Liang Zhang,1 Mengxia Li,1 Bo Deng,2 Nan Dai,1 Yan Feng,1 Jinlu Shan,1 Yuxin Yang,1 Chengyi Mao,3 Ping Huang,1 Chengxiong Xu,1 Dong Wang11Cancer Center of Daping Hospital, Third Military Medical University, Chongqing 400042, People’s Republic of China; 2Thoracic Surgery Department of Daping Hospital, Third Military Medical University, Chongqing 400042, People’s Republic of China; 3Pathology Department of Daping Hospital, Third Military Medical University, Chongqing 400042, People’s Republic of ChinaBackground: Postoperative recurrence is the main cause of a poor prognosis in early-stage lung adenocarcinoma (LUAD). Factors that can predict recurrence risk are critically needed.Materials and methods: In this study, we designed a screening procedure based on gene profile data and performed validation using TCGA and Daping hospital’s cohorts. Differentially expressed genes (DEGs) between patients with recurrence-free survival (RFS) 3 years were identified, overlapping genes among these DEGs were selected as candidate biomarkers. A Cox proportional hazards model, immunohistochemistry and Kaplan-Meier survival analysis were performed to validate these biomarkers in two distinct validation sets.Results: SFTPB, SFTPD, SFTA1P, HLA-DQB1, ITGB8, ANLN, and LRRN1 were overlapped both in TCGA and Daping discovery sets. The Cox proportional hazards model analysis of the TCGA validation set showed that HLA-DQB1 was an independent prognostic factor for RFS (HR=0.686, 95% CI, 0.542–0.868). Immunohistochemistry and Kaplan-Meier analysis in Daping validation sets confirmed HLA-DQB1 expression on tumor cells (not interstitial cells) to be an effective predictor of postoperative recurrence. Further examination revealed that the level of HLA-DQB1 expression on tumor cells was positively correlated with CD4- and CD8-positive lymphocyte infiltration into the tumor.Conclusion: All results indicate that high expression of HLA-DQB1 on tumor cells is a good prognostic marker in early-stage LUAD, and the mechanism may be related to anti-tumor immune activity.Keywords: HLA-DQB1, lung adenocarcinoma, tumor recurrence, prognostic factor

Abstract Background Infection with the hepatitis B virus (HBV) is an independent risk factor for liver cirrhosis and hepatocellular carcinoma, polymorphisms in HLA-DQB1 play an important role in HBV infections. Methods This study examined the relationships between HLA-DQB1 alleles and HBV infection susceptibility among 256 HBV carriers and 433 healthy controls. Venous blood samples were subjected to DQB1 high-resolution typing and testing for interferon-gamma, interleukin-4 (IL-4), interleukin-10, and DQB1 mRNA expression. A meta-analysis was also performed using relevant case–control studies that evaluated the associations of HLA-DQB1 alleles with HBV infection and clearance. Results We found that HLA-DQB1*06:03 protected against HBV infection. Levels of IFN-γ and IL-4 were significantly elevated in HBV cases with HLA-DQB1*06:05 (vs. HLA-DQB1*05:03), and the HBV group had higher DQB1 mRNA expression than the healthy control group with HLA-DQB1*05:03 and HLA-DQB1*06:02. The meta-analysis revealed that HLA-DQB1*04:01, HLA-DQB1*05:02, HLA-DQB1*05:03, and HLA-DQB1*06:01 were risk factors for HBV infection susceptibility, while HLA-DQB1*05:01, HLA-DQB1*06:03, and HLA-DQB1*06:04 protected against HBV infection. Spontaneous HBV clearance was associated withHLA-DQB1*06:04, while chronic HBV infection was associated with HLA-DQB1*02:01 and HLA-DQB1*05:02. Conclusion DBQ1 typing can be used to identify patients who have elevated risks of HBV infection (i.e., patients with HLA-DQB1*04:01, HLA-DQB1*05:02, HLA-DQB1*05:03, and HLA-DQB1*06:01) or elevated risks of chronic HBV infection (i.e., patients with HLA-DQB1*02:01 and HLA-DQB1*05:02).

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 < 0.0001; TT vs. AA: OR = 8.72, 95% CI = 3.87–19.7, p < 0.0001; AT+TT vs. AA: OR = 3.87, 95% CI = 2.61–5.73, p < 0.0001; T vs. A: OR = 2.97, 95% CI = 2.20–4.01, p < 0.0001) except the recessive model which showed a significantly reduced risk (TT vs. AA+AT: OR = 0.20, 95% CI = 0.09–0.44, p = 0.0001). rs9272143 showed significantly reduced risk for the additive model 1, dominant model, and allelic model (TC vs. TT: OR = 0.46, 95% CI = 0.31–0.70, p = 0.0004; TC+CC vs. TT: OR = 0.47 95% CI = 0.32–0.70, p = 0.0002; C vs. T: OR = 0.56, 95% CI = 0.40–0.78, p = 0.0006, respectively). The third variant, rs7780883, was significantly associated with increased risk in additive model 2, dominant, and allelic models (AA vs. GG: OR = 5.08, 95% CI = 2.45–10.5, p < 0.0001; GA+AA vs. GG: OR = 1.54, 95% CI = 1.06–2.24, p = 0.0237; A vs. G: OR = 1.88, 95% CI = 1.34–2.52, p < 0.0001, consecutively), whereas recessive model reduced the risk of cervical cancer (AA vs. GG+GA: OR = 0.20, 95% CI = 0.09–0.41, p < 0.0001). Other models of these SNPs were not associated with cervical cancer. All significant associations for three SNPs withstand after Bonferroni correction except the additive model 2 of rs7780883. Conclusion: Our study concludes that INSIG2 rs6726538, HLA‐DRB1 rs9272143, and GCNT1P5 rs7780883 polymorphisms may contribute to the development of cervical cancer in the Bangladeshi population. [ABSTRACT FROM AUTHOR]

Given the potential link between genetic risk factors and clinical features of systemic lupus erythematosus (SLE), this study aimed to explore the relationship between human leukocyte antigen (HLA)-DRB1/DQB1 alleles and haplotypes and clinical sub-phenotypes of the disease in a group of Iranian SLE patients. HLA-DRB1 and HLA-DQB1 alleles were determined by PCR-SSP in 127 SLE patients and 153 ethnically-matched healthy controls. The relationships between various clinical manifestations and HLA alleles/haplotypes were analyzed in the patients. We observed the positive associations of DRB1*07 and DRB1*07-DQB1*02 haplotypes with articular and pulmonary involvement (p=0.006 and p

IgG4 autoimmune diseases (IgG4-AID) are an emerging group of autoimmune diseases that are caused by pathogenic autoantibodies of the IgG4 subclass. It has only recently been appreciated, that members of this group share relevant immunobiological and therapeutic aspects even though different antigens, tissues and organs are affected: glomerulonephritis (kidney), pemphigus vulgaris (skin), thrombotic thrombocytopenic purpura (hematologic system) muscle-specific kinase (MuSK) in myasthenia gravis (peripheral nervous system) and autoimmune encephalitis (central nervous system) to give some examples. In all these diseases, patients’ IgG4 subclass autoantibodies block protein-protein interactions instead of causing complement mediated tissue injury, patients respond favorably to rituximab and share a genetic predisposition: at least five HLA class II genes have been reported in individual studies to be associated with several different IgG4-AID. This suggests a role for the HLA class II region and specifically the DRβ1 chain for aberrant priming of autoreactive T-cells toward a chronic immune response skewed toward the production of IgG4 subclass autoantibodies. The aim of this review is to provide an update on findings arguing for a common pathogenic mechanism in IgG4-AID in general and to provide hypotheses about the role of distinct HLA haplotypes, T-cells and cytokines in IgG4-AID.

IgG4 autoimmune diseases (IgG4-AID) are an emerging group of autoimmune diseases that are caused by pathogenic autoantibodies of the IgG4 subclass. It has only recently been appreciated, that members of this group share relevant immunobiological and therapeutic aspects even though different antigens, tissues and organs are affected: glomerulonephritis (kidney), pemphigus vulgaris (skin), thrombotic thrombocytopenic purpura (hematologic system) muscle-specific kinase (MuSK) in myasthenia gravis (peripheral nervous system) and autoimmune encephalitis (central nervous system) to give some examples. In all these diseases, patients' IgG4 subclass autoantibodies block protein-protein interactions instead of causing complement mediated tissue injury, patients respond favorably to rituximab and share a genetic predisposition: at least five HLA class II genes have been reported in individual studies to be associated with several different IgG4-AID. This suggests a role for the HLA class II region and specifically the DRβ1 chain for aberrant priming of autoreactive T-cells toward a chronic immune response skewed toward the production of IgG4 subclass autoantibodies. The aim of this review is to provide an update on findings arguing for a common pathogenic mechanism in IgG4-AID in general and to provide hypotheses about the role of distinct HLA haplotypes, T-cells and cytokines in IgG4-AID. [ABSTRACT FROM AUTHOR]

Given the potential link between genetic risk factors and clinical features of systemic lupus erythematosus (SLE), this study aimed to explore the relationship between human leukocyte antigen (HLA)-DRB1/DQB1 alleles and haplotypes and clinical sub-phenotypes of the disease in a group of Iranian SLE patients. HLA-DRB1 and HLA-DQB1 alleles were determined by PCR-SSP in 127 SLE patients and 153 ethnically-matched healthy controls. The relationships between various clinical manifestations and HLA alleles/haplotypes were analyzed in the patients. We observed the positive associations of DRB1*07 and DRB1*07-DQB1*02 haplotypes with articular and pulmonary involvement (p=0.006 and p<0.001 respectively), DRB1*03 and DQB1*02 alleles, and DRB1*03-DQB1*02 haplotypes with cutaneous (p=0.03, p=0.004 and p=0.02 respectively) and renal involvement, and DRB1*13 as well as DRB1*13-DQB1*06 haplotypes with renal involvement. Conversely, negative associations of DRB1*13 with cutaneous and gastrointestinal disorders (p=0.004 and p=0.02 respectively) and DRB1*01 with renal involvement (p=0.03) were found in our patients. Patients carrying susceptible HLA-DRB1 alleles had a higher risk for expression of cutaneous involvement (p=0.03), anti-coagulant antibody development (p=0.01), and a lower risk for pulmonary disorders compared to patients' negatives for susceptible alleles (p=0.04). Our findings on associations between HLA risk allele (DRB1*03) as well as non-risk alleles with particular clinical manifestations and between the potentially protective allele (DRB1*01) and protection against renal involvement indicate the important role of HLA class II genes in predisposing of specific serological and clinical features of SLE disease which could be implicative for therapeutic applications and better management of SLE patients. [ABSTRACT FROM AUTHOR]

Background: Colon cancer (CC) is one of the most common malignancies worldwide. Characterization of new prognostic biomarkers for right-sided CC (RCC) and left-sided CC (LCC) may contribute to improving early detection. An association of human leukocyte antigens class II (HLA-II) with the predisposition to CC was suggested., Aim of the Study: We evaluated the association of DRB1 and DQB1 with the risk of LCC and RCC., Patients and Methods: Our study comprised 93 CC patients and 100 healthy controls. Genotyping of HLA class II alleles were performed by the Polymerase Chain Reaction Sequence-Specific Primers (PCR-SSP)., Results: DRB1*03 was positively associated with CC. In contrast, DRB1*11, DRB1*13, DQB1*03, and DQB1*05 were negatively linked to CC. Haplotype analysis revealed that DRB1*04-DQB1*04 and DRB1*09-DQB1*02 were positive, while DRB1*01-DQB1*05, DRB1*04-DQB1*03, DRB1*07-DQB1*02, DRB1*11-DQB1*03, DRB1*11-DQB1*05, and DRB1*13-DQB1*06 were negatively associated with CC. For sigmoid CC, DRB1*13, DRB1*11, and DQB1*05 were negative, while DRB1*04-DQB1*02, and DRB1*07-DQB1*03 were positively associated. DRB1*03 and DRB1*04-DQB1*04 were positive, while DRB1*11 and DQB1*03 were negatively linked to RCC. According to the LCC, DRB1*07, DRB1*11, DQB1*03, DQB1*05, and DRB1*07-DQB1*02 were negative. In contrast, DRB1*09-DQB1*02 was positively associated with LCC. Stratified analysis revealed that DRB1*11 is associated with higher risk of metastasis in CC and sigmoid CC, and tolerance to treatment in RCC. DQB1*03 was associated with lymph-node invasion in CC., Conclusion: DRB1 and DQB1 polymorphisms could be used as future biomarkers for the early detection of subjects at a higher risk of developing RCC and LCC, metastasis in sigmoid CC, and tolerance to treatment in RCC., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: We aimed to determine Human Leukocyte Antigen (HLA)-DRB1, DQB1, and MHC Class I related chain A (MICA) genotypes in patients with ulcerative colitis. Methods: HLA-DRB1, HLA-DQB1, MICA genotyping of patient (n:85) and controls (n:100) were performed by PCR-SSO Luminex (One Lambda genotyping kit). Results: We found significantly higher DRB1*01 (p:0.022, OR:0.23, CI:0.06–0.8) and MICA*0002/20/55 (p:0.03, OR:0.53, CI:0.29–0.93) alleles in control group whereas DRB1*14 (p:0.04, OR:2.25, CI:1–5.08), DRB1*15 (p:<0.0001, OR:4.54, CI:2.09–9.88) and MICA*0004 (p:0.01, OR:2.84, CI:1.2–6.7) alleles were higher in patient group. Conclusions: The present study will inform the MICA and HLA genotypes about the protective (DRB1*01, MICA*0002/20/55) or susceptible (DRB1*14, DRB1*15, MICA*0004) alleles of the disease and helps the literature on Turkish patients with ulcerative colitis. [ABSTRACT FROM AUTHOR]

A novel variant of HLA‐DQB1*03 differs from DQB1*03:02:01:01 by one nucleotide substitution in Exon 2. [ABSTRACT FROM AUTHOR]

Abstract Background Ankylosing spondylitis (AS) is a chronic rheumatic and autoimmune disease. Little is known about the potential role of DNA methylation in the pathogenesis of AS. This study was undertaken to explore the potential role of DNA methylation in the genetic mechanism of AS. Methods In this study, we compared the genome-wide DNA methylation profiles of peripheral blood mononuclear cells (PBMCs) between five AS patients and five healthy subjects, using the Illumina Infinium HumanMethylation450 BeadChip. Quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) was performed to validate the relevance of the identified differentially methylated genes for AS, using another independent sample of five AS patients and five healthy subjects. Results Compared with healthy controls, we detected 1915 differentially methylated CpG sites mapped to 1214 genes. The HLA-DQB1 gene achieved the most significant signal (cg14323910, adjusted P = 1.84 × 10–6, β difference = 0.5634) for AS. Additionally, the CpG site cg04777551 of HLA-DQB1 presented a suggestive association with AS (adjusted P = 1.46 × 10–3, β difference = 0.3594). qRT-PCR observed that the mRNA expression level of HLA-DQB1 in AS PBMCs was significantly lower than that in healthy control PBMCs (ratio = 0.48 ± 0.10, P

HLA-DMB allele frequencies and HLA-DBM-DRB1-DQB1 extended haplotypes were studied for the first time in Amerindians (Cuenca city area, Ecuador). It was found that most common extended haplotypes gathered the most frequent HLA-DRB1 Amerindian alleles. HLA-DMB polymorphism studies may be important to uncover HLA and diseases pathogenesis and also in an extended HLA haplotype frameshift. HLA-DM molecule has a crucial role together with CLIP protein in HLA class II peptide presentation. HLA extended haplotypes including complement and non classical genes alleles are proposed to HLA and disease studies. [ABSTRACT FROM AUTHOR]

Background: Although the precise mechanisms underlying the efficacy of allergen‐specific immunotherapy (AIT) are not clear, some evidence suggests that this may be linked to polymorphisms in HLA‐II gene. We aimed to investigate the correlation between HLA‐II gene polymorphisms and house dust mite (HDM)‐specific immunotherapy efficacy, and evaluate specific polymorphisms as potential biomarkers in allergic rhinitis (AR) patients who would benefit most from AIT. Methods: Fifty‐one Han Chinese patients with AR receiving HDM AIT were recruited. Genomic DNA was extracted from venous blood samples and genotyped for HLA‐DRB1 and HAL‐DQB1 alleles using the polymerase chain reaction sequence‐based genotyping method. Nasal and eye symptoms were investigated based on visual analogue scale and rhinoconjunctivitis quality of life. Results: Allele DRB1*04:06; DRB1*14:05 showed a positive correlation with improvements in nasal blockage, nasal itching, eye itching, and activities. Similarly, DQB1*03:02:01; DQB1*05:03: 01 was positively correlated with improvements in nose blocking, nasal itching, eye itching, behavioral problems, and nasal symptoms scores; and DRB1*03:01; DRB1*04:06 positively correlated with nasal symptoms scores. In contrast, DRB1*07:01:01; DRB1*11:01 was negatively correlated with non‐pollen symptoms, behavioral problems, and nasal symptoms. Conclusion: HLA‐DRB1 and HLA‐DQB1 gene polymorphism are associated with AIT efficacy in HDM‐sensitive Chinese patients with AR, of which DRB1*03:01; DRB1*04:06 and DQB1*03:02:01; DQB1*05:03:01 may be useful biomarkers of AR patient candidacy for effective AIT. [ABSTRACT FROM AUTHOR]

Background: Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is an uncommon T-cell lymphoma associated with textured-surface breast implants. Human leukocyte antigen (HLA) polymorphisms have been described with other forms of lymphoma, but have not been described for BIA-ALCL.Objectives: The aim of this study was to evaluate HLA polymorphisms in BIA-ALCL patients.Methods: We prospectively evaluated HLA alleles in patients with BIA-ALCL. HLA was analyzed by probe-based sequence-specific testing and sequence-based typing. The frequencies of HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 alleles were evaluated. Allele frequencies in the Caucasian European general population were obtained from the National Marrow Donor Program to serve as normative controls. We estimated the relative risk of BIA-ALCL with 95% confidence intervals from a t test.Results: Thirteen patients who had undergone BIA-ALCL and HLA testing were identified from 2017 to 2018. Patients carried 10, 11, and 9 HLA-A, HLA-B, and HLA-C alleles, respectively. There were 8 DRB1 alleles and 5 DQB1 alleles in the BIA-ALCL patients. The A*26 allele occurred significantly more frequently in the general population compared with BIA-ALCL patients (0.2992 vs 0.07692, P < 0.001).Conclusions: Our results identify a difference between HLA A*26 in patients who develop BIA-ALCL and the general population, and may signify genetic susceptibility factors responsible for germline genetic variation in HLA in patients with BIA-ALCL. Further work is needed to elucidate if these alleles are predictive for BIA-ALCL in women with textured-surface breast implants.Level of Evidence: 4. [ABSTRACT FROM AUTHOR]

Three new DQB1*03:02:33, DQB1*04:79 and DQB1*05:249 alleles detected in Russian individuals by next‐generation sequencing. [ABSTRACT FROM AUTHOR]

The potential impact of human leukocyte antigen (HLA) genotype variations on development of diabetic peripheral neuropathy (DPN) is not well determined. This study aimed to identify the association of HLA class II alleles with DPN in type 2 diabetes (T2D) patients. Totally 106 T2D patients, 49 with DPN and 57 without DPN, and 100 ethnic-matched healthy controls were analyzed. Both groups of the patients were matched based on sex, age, body mass index (BMI) and duration of T2D. Polyneuropathy was diagnosed using electrodiagnostic methods. HLA-DRB1 and DQB1 genotyping was performed in all subjects by the polymerase chain reaction with sequence-specific primers (PCR-SSP) method. T2D patients with DPN showed higher frequencies of HLA-DRB1*10 and DRB1*12 alleles compared to control group (P = 0.04). HLA-DQB1*02 allele and HLA-DRB1*07-DQB1*02 haplotype were associated with a decreased risk for developing DPN in T2D patients (P = 0.02 and P = 0.05 respectively). Also, patients with severe neuropathy showed higher frequencies of DRB1*07 (P = 0.003) and DQB1*02 (P = 0.02) alleles than those with mild-to-moderate form of neuropathy. The distribution of DRB1 and DQB1 alleles and haplotypes were not statistically different between all patients and healthy controls. Our findings implicate a possible protective role of HLA-DQB1*02 allele and HLA-DRB1*07-DQB1*02 haplotype against development of peripheral neuropathy in T2D patients. Therefore, variations in HLA genotypes might be used as genetic markers for prediction and potentially management of neuropathy in T2D patients.

HLA‐DQB1*06:427 differs from HLA‐DQB*06:01:01:01 by a single non‐synonymous nucleotide substitution in codon 83 of exon 2. [ABSTRACT FROM AUTHOR]