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Genomic full‐length sequence of HLA‐B*40:96 was identified by a group‐specific sequencing approach in a Chinese individual. [ABSTRACT FROM AUTHOR]

The HLA genes are associated with various autoimmune pathologies, with the control of the immune response also being significant in organs and cells transplantation. The aim of the study is to identify the HLA-A, HLA-B, and HLA-C alleles frequencies in the analyzed Romanian cohort. We performed HLA typing using next-generation sequencing (NGS) in a Romanian cohort to estimate class I HLA allele frequencies up to a six-digit resolution. A total of 420 voluntary donors from the National Registry of Voluntary Hematopoietic Stem Cell Donors (RNDVCSH) were included in the study for HLA genotyping. Peripheral blood samples were taken and brought to the Fundeni Clinical Institute during 2020–2021. HLA genotyping was performed using the Immucor Mia Fora NGS MFlex kit. A total of 109 different alleles were detected in 420 analyzed samples, out of which 31 were for HLA-A, 49 for HLA-B, and 29 for HLA-C. The most frequent HLA-A alleles were HLA-A*02:01:01 (26.11%), HLA-A*01:01:01 (12.5%), HLA-A*24:02:01 (11.67%), HLA-A*03:01:01 (9.72%), HLA-A*11:01:01, and HLA-A*32:01:01 (each with 8.6%). For the HLA-B locus, the most frequent allele was HLA-B*18:01:01 (11.25%), followed by HLA-B*51:01:01 (10.83%) and HLA-B*08:01:01 (7.78%). The most common HLA-C alleles were HLA-C*07:01:01 (17.36%), HLA-C*04:01:01 (13.47%), and HLA-C*12:03:01 (10.69%). Follow-up studies are ongoing for confirming the detected results. [ABSTRACT FROM AUTHOR]

Background: Amoxicillin (AMX) is among the most prescribed and the best tolerated antimicrobials worldwide. However, it can occasionally trigger severe cutaneous adverse reactions (SCAR) with a significant morbidity and mortality. The genetic factors that may be relevant to AMX-induced SCAR (AMX-SCAR) remain unclear. Identification of the genetic risk factor may prevent patients from the risk of AMX exposure and resume therapy with other falsely implicated drugs. Methodology: Four patients with AMX-SCAR, 1,000 population control and 100 AMX-tolerant individuals were enrolled in this study. Both exome-wide and HLA-based association studies were conducted. Molecular docking analysis was employed to simulate the interactions between AMX and risk HLA proteins. Results: Compared with AMX-tolerant controls, a significant association of HLAB* 15:01 with AMX-SCAR was validated [odds ratio (OR) = 22.9, 95% confidence interval (CI): 1.68-1275.67; p=7.34 × 10-3]. Moreover, 75% carriers of HLA-B*15:01 in four patients with AMX-SCAR, and the carrier frequency of 10.7% in 1,000 control individuals and 11.0% in 100 AMX-tolerant controls, respectively. Within HLA-B protein, the S140 present in all cases and demonstrated the strongest association with AMX-SCAR [OR = 53.5, p = 5.18 × 10-4]. Molecular docking results also confirmed the interaction between AMX and S140 of the HLA-B protein, thus eliminating the false-positive results during in association analysis. Conclusion: Our findings suggest that genetic susceptibility may be involved in the development of AMX-SCAR in Han Chinese. However, whether the HLA-B variants observed in this study can be used as an effective genetic marker of AMXinduced SCAR still needs to be further explored in larger cohort studies and other ethnic populations. [ABSTRACT FROM AUTHOR]

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

Globally, SARS-CoV-2 has negatively impacted many lives and industries due to its rapid spread, severe outcomes, and the need for the implementation of lockdown strategies across the world. SARS-CoV-2 disease severity varies among different populations. Host genetics have been associated with various diseases, and their ability to alter disease susceptibility and severity. In addition, Human Leukocyte Antigen (HLA) expression levels and alleles vary significantly among ethnic groups, which might impact the host's response to SARS-CoV-2. Our previous study highlighted that HLA-A might have an effect on COVID-19 disease severity across ethnicities. Therefore, in this study, we aim to examine the effect of HLA-B and C expression levels on COVID-19 disease severity. To achieve this, we used real-time PCR to measure the HLA mRNA expression levels of SARS-CoV-2-infected individuals from a South African cohort and compared them across ethnic groups, disease outcomes, gender, comorbidities, and age. Our results show (1) that the effect of HLA-B mRNA expression levels was associated with differences in disease severity when we compare symptomatic vs. asymptomatic (p < 0.0001). While HLA-C mRNA expression levels were not associated with COVID-19 disease severity. (2) In addition, we observed that HLA-B and HLA-C mRNA expression levels were significantly different between South African Black individuals and South African Indian individuals (p < 0.0001, p < 0.0001). HLA-B mRNA expression levels among symptomatic South African Black individuals were significantly higher than symptomatic South African Indian individuals (p < 0.0001). In addition, the HLA-B mRNA expression levels of symptomatic South African Black individuals were significantly higher than asymptomatic South African Black individuals (p > 0.0001). HLA-C mRNA expression levels among symptomatic South African Black individuals were significantly higher than among symptomatic South African Indian individuals (p = 0.0217). (3) HLA-C expression levels were significantly different between males and females (p = 0.0052). In addition, the HLA-C expression levels of asymptomatic males are higher than asymptomatic females (p = 0.0375). (4) HLA-B expression levels were significantly different between individuals with and without comorbidities (p = 0.0009). In addition, we observed a significant difference between individuals with no comorbidities and non-communicable diseases (p = 0.0034), in particular, hypertension (p = 0.0487). (5) HLA-B expression levels were significantly different between individuals between 26–35 and 56–65 years (p = 0.0380). Our work is expected to strengthen the understanding of the relationship between HLA and COVID-19 by providing insights into HLA-B and C expression levels across ethnic populations in South Africa among COVID-19-symptomatic and asymptomatic individuals. Our results highlight that HLA-B mRNA expression levels contribute to COVID-19 severity as well as variation in ethnicities associated with COVID-19. Further studies are needed to examine the effect of HLA expression levels across various ethnic groups with contributing factors. [ABSTRACT FROM AUTHOR]

Eight novel HLA class I alleles detected by next‐generation sequencing. [ABSTRACT FROM AUTHOR]

Background: Oxcarbazepine is thought to be better-tolerated and less susceptible to drug–drug interactions than its predecessor, carbamazepine. Genetic testing for HLA-B*15:02 is recommended in specific populations to identify those at high risk of severe hypersensitivity reactions; however, other pharmacologic and pharmacogenetic factors that can impact drug disposition may be involved. Methods: We present a case of an 8-year-old boy treated with oxcarbazepine who developed drug reaction with eosinophilia and systemic symptoms (DRESS) with Stevens–Johnsons syndrome overlap and was negative for HLA-B*15:02. We review the extant literature related to oxcarbazepine disposition, and potential pharmacogenetic variants in aldoketoreductase 1C (AKR1C)2–4 that may contribute to this risk. Results: Genetic variability in oxcarbazepine disposition pathways may contribute to tolerability and toxicity, including the development of hypersensitivity reactions. Conclusions: While preemptive genetic testing for HLA-B*15:02 in individuals of Asian ancestry is recommended to prevent severe hypersensitivity reactions to oxcarbazepine, oxcarbazepine concentrations and AKR1C variation may contribute to the risk of severe adverse reactions. We provide recommendations for future study to elucidate whether these individual factors are important for reducing the risk of severe adverse events. [ABSTRACT FROM AUTHOR]

Eight novel HLA class I alleles have been identified using full gene sequencing. [ABSTRACT FROM AUTHOR]

The novel HLA‐B*18:37:03 allele, first described in a potential bone marrow donor from Brazil. [ABSTRACT FROM AUTHOR]

HLA‐B*49:01:01:22 differs from HLA‐B*49:01:01:01 by a single nucleotide C‐>G change in intron 5 at gDNA 2451. [ABSTRACT FROM AUTHOR]

B*54:47 allele differs from B*54:01:01:01 in codon 74 in exon 2. [ABSTRACT FROM AUTHOR]

Whether polymorphic Human Leukocyte Antigen (HLA)-A, HLA-B and HLA-DRB1 alleles were associated with acute liver disease after hepatitis B virus (HBV) infections was investigated. In this study, from initially 100 participants in each group, HLA-A, HLA-B and HLA-DRB1 sequences were available from 86 acute hepatitis B (AHB) patients and from 84 HBV-resistant individuals (controls), using sequencing-based typing allele groups and alleles that exhibited differences in distribution between the case and control groups were subjected to chi-squared and logistic regression analyses to identify those associated with AHB. A dose response analysis was also performed on the effect of HLA-A*24:02 allele number on acute liver disease following HBV infection. The frequency distribution of HLA-B and HLA-DRB1 alleles in the control group were in Hardy-Weinberg Equilibrium (P >.05). HLA-A*24:02 (χ2 = 6.949, P =.008) occurred most frequently in the AHB and HLA-DRB1*12:02 (χ2 = 7.768, P =.005) in the control group. With adjustment for sex, the logistic regression model showed that the HLA-A*24:02 allele was significantly associated with AHB liver injury (P =.0326, OR = 2.270, 95% CI: 1.070–4.816), whereas the other HLA-A, HLA-B, and HLA-DRB1 alleles were not (P >.05). A linear response was observed for the association between HLA-A*24:02 allele number and acute liver disease after HBV infections (χ2 = 4.428, P =.025). The HLA-A*24:02 allele may influence the severity of the cellular response to HBV infection, increasing the elimination of HBV-infected hepatocytes. The HLA-A*24:02 allele may be a potential screening marker for identifying people or regional populations in China at higher risk of acute liver disease following HBV infection. [ABSTRACT FROM AUTHOR]

HLA‐B is among the most variable gene in the human genome. This gene encodes a key molecule for antigen presentation to CD8+ T lymphocytes and NK cell modulation. Despite the myriad of studies evaluating its coding region (with an emphasis on exons 2 and 3), few studies evaluated introns and regulatory sequences in real population samples. Thus, HLA‐B variability is probably underestimated. We applied a bioinformatics pipeline tailored for HLA genes on 5347 samples from 80 different populations, which includes more than 1000 admixed Brazilians, to evaluate the HLA‐B variability (SNPs, indels, MNPs, alleles, and haplotypes) in exons, introns, and regulatory regions. We observed 610 variable sites throughout HLA‐B; the most frequent variants are shared worldwide. However, the haplotype distribution is geographically structured. We detected 920 full‐length haplotypes (exons, introns, and untranslated regions) encoding 239 different protein sequences. HLA‐B gene diversity is higher in admixed populations and Europeans while lower in African ancestry individuals. Each HLA‐B allele group is associated with specific promoter sequences. This HLA‐B variation resource may improve HLA imputation accuracy and disease‐association studies and provide evolutionary insights regarding HLA‐B genetic diversity in human populations. [ABSTRACT FROM AUTHOR]

In order to expand the promise of regenerative medicine using allogeneic induced pluripotent stem cells (iPSCs), precise and efficient genome editing of human leukocyte antigen (HLA) genes would be advantageous to minimize the immune rejection caused by mismatches of HLA type. However, clinical-grade genome editing of multiple HLA genes in human iPSC lines remains unexplored. Here, we optimized the protocol for good manufacturing practice (GMP)-compatible CRISPR-Cas9 genome editing to deplete the three gene locus (HLA-A, HLA-B, and CIITA genes) simultaneously in HLA homozygous iPSCs. The use of HLA homozygous iPSCs has one main advantage over heterozygous iPSCs for inducing biallelic knockout by a single gRNA. RNA-seq and flow cytometry analyses confirmed the successful depletion of HLAs, and lineage-specific differentiation into cardiomyocytes was verified. We also confirmed that the pluripotency of genome-edited iPSCs was successfully maintained by the three germ layers of differentiation. Moreover, whole-genome sequencing, karyotyping, and optical genome mapping analyses revealed no evident genomic abnormalities detected in some clones, whereas unexpected copy number losses, chromosomal translocations, and complex genomic rearrangements were observed in other clones. Our results indicate the importance of multidimensional analyses to ensure the safety and quality of the genome-edited cells. The manufacturing and assessment pipelines presented here will be the basis for clinical-grade genome editing of iPSCs.

HLA‐B*13:179 differs from HLA‐B*13:99 by one nucleotide substitution at position 829(A>G) in exon 4. [ABSTRACT FROM AUTHOR]

HLA‐B*14:118 differs from HLA‐B*14:93 by two non‐synonymous and one synonymous nucleotide substitution in exon 2. [ABSTRACT FROM AUTHOR]

The coding sequence of HLA‐B*40:540N differs from HLA‐B*40:02:01:01 by a non‐synonymous nucleotide substitution in exon 3. [ABSTRACT FROM AUTHOR]

The novel HLA‐B*18:243 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]

We examined the correlation between class I HLA evolutionary divergence (HED), a surrogate for the capacity to present different peptides, and the outcomes of 234 adult inpatients with confirmed SARS-CoV-2 infection. Genomic DNA was extracted from peripheral blood and genotyped by next-generation sequencing (NGS). HED scores for HLA class I (HLA-A, -B, and -C) genotypes were calculated using Grantham's distance. Higher HED scores for HLA-B, but not HLA-A or -C, are significantly associated with a decreased probability of poor outcomes including ICU admission, mechanical ventilation, and death (OR = 0.93; P = 0.04) in the univariate analysis. In the multivariate analysis, increased HLA-B HED score, younger age, and no comorbidity were independently associated with favorable outcomes (P = 0.02, P = 0.01, and P = 0.05, respectively). This finding is consistent with the notion that broader peptide repertoires presented by class I HLA may be beneficial in infection control. [ABSTRACT FROM AUTHOR]

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.

Abstract Objectives To determine the association of Human leukocyte antigen B (HLA‑B) alleles with ankylosing spondylitis and the allelic association of HLA‐B27 with endoplasmic reticulum aminopeptidase 1 (ERAP1) single‐nucleotide polymorphism (SNP) rs30187 in patients with ankylosing spondylitis (AS). Methods We studied 48 consecutively enrolled well‐defined AS patients and 48 healthy controls recruited from the outpatient clinic of the rheumatology department of Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh. To genotype HLA‐B alleles from peripheral blood DNA, we designed sequence‐specific primers for polymerase chain reaction. Sanger's sequencing method was used to detect the ERAP1 rs30187 SNP. The HLA‐B allele distributions were compared between cases and controls. To infer an allelic association between HLA‐B27 and ERAP1, allele distributions from both loci were compared using cross‐tabulations. Chi‐squared test or Fisher's exact test was used to quantify the association, and their strength of association was tested by odds ratio (OR) with 95% confidence interval (CI). Results The frequency of HLA‐B27 was found to be higher in AS patients (60.4%) than in healthy controls (8.3%). HLA‐B27 allele had an OR of 16.8 (95% CI = 5.2–54.4) for the development of AS. Overall, 4% of AS patients had both HLA‐B27 and HLA‐B40. No significant association was found between ERAP1 rs30187 SNP and HLA‐B27 in patients with AS (OR = 1.7, 95% CI = 0.5–5.6). Conclusions HLA‐B27 was significantly associated with AS in patients in Bangladesh. However, no association between ERAP1 rs30187 SNP and HLA‐B27 was observed.

Antipsychotic-induced parkinsonism is an undesirable reaction from the extrapyramidal system that occurs against the background of taking antipsychotics (AP), more often in patients with schizophrenia. Antipsychotic-induced parkinsonism belongs to the group of secondary parkinsonism. Its prevalence in the world is about 36%. It is assumed that this undesirable AP reaction is genetically determined. In recent years, numerous associative genetic studies of predisposition to the development of antipsychotic-induced parkinsonism have been conducted. However, the research results are contradictory.Purpose. Review of the results of studies of genetic predictors of antipsychotic-induced parkinsonism in patients with schizophrenia.Materials and methods. We searched for full-text publications in Russian and English in the RSCI, PubMed, Web of Science, Springer databases using keywords and combined searches for words over the past decade.Results. The review considers candidate genes encoding proteins/enzymes involved in the pharmacodynamics and pharmacokinetics of AP. We analyzed 23 genome-wide studies examining 108 genetic variations, including SNV/polymorphisms of 26 candidate genes involved in the development of AIP in schizophrenic patients. Among such a set of obtained results, only 22 positive associations were revealed: rs1799732 (141CIns/Del), rs1800497 (C/T), rs6275 (C/T) DRD2; rs167771 (G/A) DRD3; VNTR*9R DAT1; rs4680 (G/A) СOMT; rs6311 (C/T) 5HTR2A; rs6318 (C/G), rs3813929 (С/Т), haplotype-997G, -759C, -697C и 68G HTR2C; rs2179652 (C/T), rs2746073 (T/A), rs4606 (C/G), rs1152746 (A/G), rs1819741 (С/Т), rs1933695 (G/A), haplotype rs1933695-G, rs2179652-C, rs4606-C, rs1819741-T и rs1152746-G, haplotype rs1933695-G, rs2179652-T, rs4606-G, rs1819741-C и rs1152746-A RGS2; haplotype TCCTC ADORA2A; rs4795390 (C/G) PPP1R1B; rs6265 (G/A) BDNF; rs12678719 (C/G) ZFPM2; rs938112 (C/A) LSMAP; rs2987902 (A/T) ABL1; HLA-B44; rs16947 (A/G), rs1135824 (A/G), rs3892097 (A/G), rs28371733 (A/G), rs5030867 (A/C), rs5030865 (A/C), rs1065852 (C/T), rs5030863 (C/G), rs5030862 (A/G), rs28371706 (C/T), rs28371725 (A/G), rs1080983 (A/G) CYP2D6. However, at the present time it should be recognized that there is no final or unique decision about the leading role of any particular SNV/polymorphism in the development of AIP.Conclusion. Disclosure of genetic predictors of AP-induced parkinsonism development may provide a key to the development of a strategy for personalized prevention and treatment of the neurological complication of AP-therapy of schizophrenia in real clinical practice.

The novel HLA‐B*39:189 allele was characterized using next generation sequencing technology. [ABSTRACT FROM AUTHOR]

HLA‐B*58:138 differs from HLA‐B*58:01:01:01 by one nucleotide substitution in exon 3 at codon 145. [ABSTRACT FROM AUTHOR]

Compared with HLA‐B*40:01:02:01, the alleles HLA‐B*40:495 and HLA‐B*40:512 each show one nucleotide substitution, respectively. [ABSTRACT FROM AUTHOR]

Background: HLA and NLRP3 play an important role in the development of various autoimmune and autoinflammatory diseases. Gout is an autoinflammatory disease associated with multiple genetic and environmental factors. The objective of the present study was to evaluate the interaction and association between genetic polymorphisms of HLA-B and the NLRP3 gene in Mexican patients with gout. Methods and results: Eighty-one patients with gout were included and compared with 95 healthy subjects. The polymorphisms rs4349859, rs116488202, rs2734583 and rs3099844 (within the HLA-B region) and rs3806268 and rs10754558 of the NLRP3 gene were genotyped using TaqMan probes in a Rotor-Gene device. The interactions were determined using the multifactorial dimensionality reduction (MDR) method, while the associations were determined through logistic regression models. The MDR analysis revealed significant interactions between the rs116488202 and rs10754558 polymorphisms with an entropy value of 4.31% (p < 0.0001). Significant risk associations were observed with rs4349859 and rs116488202 polymorphisms (p < 0.01); however, no significant associations were observed with the polymorphisms of the NLRP3 gene. Conclusions: The results suggest that HLA-B polymorphisms and their interaction with NLRP3 may contribute to the genetic susceptibility of gout. [ABSTRACT FROM AUTHOR]

Nucleotide substitutions in the 5′UTR and exon 2 of HLA‐B*35:01:01:05 result in a novel allele, HLA‐B*35:01:77. [ABSTRACT FROM AUTHOR]

A novel HLA‐B*35 allele, officially designated HLA‐B*35:594, was identified by next‐generation sequencing. [ABSTRACT FROM AUTHOR]

HLA‐B*40:06:01:18 differs from HLA‐B*40:06:01:02 by one nucleotide change in the 5′UTR (T > C). [ABSTRACT FROM AUTHOR]

HLA‐B*58:01:40 differs from HLA‐B*58:01:01 by a single nucleotide change in exon 3, 507 C‐ > T (codon 145.3 CGC‐ > CGT). [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]

HLA‐B*07:458 has one non‐synonymous nucleotide compared with HLA‐B*07:02:01 in codon‐21. [ABSTRACT FROM AUTHOR]

Background: The HLA-B is the most polymorphic gene, play a crucial role in drug-induced hypersensitivity reactions. There is a lot of evidence associating several risk alleles to life-threatening adverse drug reactions, and a few of them have been approved as valid biomarkers for predicting life-threatening hypersensitivity reactions. Objectives: The objective of this present study is to present the progression of HLA-B pharmacogenomics (PGx) testing in the Thai population during a 10‐year period, from 2011 to 2020. Methods: This was a retrospective observational cohort study conducted at the Faculty of Medicine Ramathibodi Hospital. Overall, 13,985 eligible patients who were tested for HLA-B risk alleles between periods of 2011–2020 at the study site were included in this study. Results: The HLA PGx testing has been increasing year by year tremendously, 94 HLA-B testing was done in 2011; this has been raised to 2,880 in 2020. Carbamazepine (n = 4,069, 33%), allopurinol (n = 4,675, 38%), and abacavir (n = 3,246, 26%) were the most common drugs for which the HLA-B genotyping was performed. HLA-B*13:01, HLA-B*15:02 and HLA-B*58:01 are highly frequent, HLA-B*51:01 and HLA-B*57:01 are moderately frequent alleles that are being associated with drug induced hypersensitivity. HLA-B*59:01 and HLA-B*38:01 theses alleles are rare but has been reported with drug induced toxicity. Most of the samples were from state hospital (50%), 36% from private clinical laboratories and 14% from private hospitals. Conclusion: According to this study, HLA-B PGx testing is increasing substantially in Thailand year after year. The advancement of research in this field, increased physician awareness of PGx, and government and insurance scheme reimbursement assistance could all be factors. Incorporating PGx data, along with other clinical and non-clinical data, into clinical decision support systems (CDS) and national formularies, on the other hand, would assist prescribers in prioritizing therapy for their patients. This will also aid in the prediction and prevention of serious adverse drug reactions. [ABSTRACT FROM AUTHOR]

Background: The HLA-B is the most polymorphic gene, play a crucial role in drug-induced hypersensitivity reactions. There is a lot of evidence associating several risk alleles to life-threatening adverse drug reactions, and a few of them have been approved as valid biomarkers for predicting life-threatening hypersensitivity reactions.Objectives: The objective of this present study is to present the progression of HLA-B pharmacogenomics (PGx) testing in the Thai population during a 10‐year period, from 2011 to 2020.Methods: This was a retrospective observational cohort study conducted at the Faculty of Medicine Ramathibodi Hospital. Overall, 13,985 eligible patients who were tested for HLA-B risk alleles between periods of 2011–2020 at the study site were included in this study.Results: The HLA PGx testing has been increasing year by year tremendously, 94 HLA-B testing was done in 2011; this has been raised to 2,880 in 2020. Carbamazepine (n = 4,069, 33%), allopurinol (n = 4,675, 38%), and abacavir (n = 3,246, 26%) were the most common drugs for which the HLA-B genotyping was performed. HLA-B*13:01, HLA-B*15:02 and HLA-B*58:01 are highly frequent, HLA-B*51:01 and HLA-B*57:01 are moderately frequent alleles that are being associated with drug induced hypersensitivity. HLA-B*59:01 and HLA-B*38:01 theses alleles are rare but has been reported with drug induced toxicity. Most of the samples were from state hospital (50%), 36% from private clinical laboratories and 14% from private hospitals.Conclusion: According to this study, HLA-B PGx testing is increasing substantially in Thailand year after year. The advancement of research in this field, increased physician awareness of PGx, and government and insurance scheme reimbursement assistance could all be factors. Incorporating PGx data, along with other clinical and non-clinical data, into clinical decision support systems (CDS) and national formularies, on the other hand, would assist prescribers in prioritizing therapy for their patients. This will also aid in the prediction and prevention of serious adverse drug reactions.

Introduction: Since HLA-B*15:02 is a biomarker for carbamazepine-induced Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in certain Asian populations, the United States food and drug administration (USFDA) recommends HLA-B*15:02 screening before carbamazepine administration in Asian and other communities. Several published reports across the globe suggested a strong association of HLA-B*15 with carbamazepine-induced hypersensitivity reactions. Methods: This study was conducted to estimate the prevalence and the genetic polymorphism of HLAB* 15 in the North Indian population (N=5469) by PCR sequence-specific oligonucleotide probe (SSOP) genotyping of the HLA-B locus. Results: The total allelic variants of HLA-B*15 identified amongst the studied samples were 17. The most frequent among these was HLA-B*15:17 (2.030%). Subsequently, HLA -B* 15:01 (1.463%) and B*15:02 (1.225%) were more frequent. Further, 185 HLA-B*15 genotypes were seen among the studied population with which the most frequent were HLA-B*15:17-40:06(0.402%), HLA-B*15:17-35:03 (0.366%) and HLA-B*15:02-40:06 (0.347%). Conclusion: This information highlights the prevalence and diversity of HLA-B*15 genotyping and its importance in the screening of carbamazepineinduced SJS/TEN in the North Indian population where the prevalence of HLA-B*15 allelic variants was on the higher side. Further, this baseline information could be further explored in the understanding of the pathogenesis of the disease and may contribute valuable information for designing effective vaccines and clinical trials. [ABSTRACT FROM AUTHOR]

HLA‐B*40:01:02:47 differs from HLA‐B*40:01:02:01 by one nucleotide change in the 3′UTR at position 2739 (A>T). [ABSTRACT FROM AUTHOR]

HLA‐B*15:05:01:02 differs from HLA‐B*15:05:01:01 by one nucleotide change in intron 2 at position 517 (C > A). [ABSTRACT FROM AUTHOR]

The HLA‐B*53:69 allele differs from HLA‐B*53:01:01:01 by two nucleotide changes in exon 3. [ABSTRACT FROM AUTHOR]

HLA‐B*57:168 differs from HLA‐B*57:01:01:01 by one nucleotide substitution at codon 325 (TGC > TCC) in exon 7. [ABSTRACT FROM AUTHOR]

HLA‐B*58:01:43 differs from HLA‐B*58:01:01:01 by one synonymous nucleotide substitution in codon 197. [ABSTRACT FROM AUTHOR]

Four new HLA‐B alleles were identified in Brazilian individuals using next generation sequencing. [ABSTRACT FROM AUTHOR]

The novel HLA‐B*49:81 allele differs by one nucleotide change from HLA‐B*49:01:01. [ABSTRACT FROM AUTHOR]

HLA‐B*37:108 and ‐B*38:108, two novel alleles detected in Russian individuals by next generation sequencing. [ABSTRACT FROM AUTHOR]

One nucleotide substitution in codon 336 of HLA‐B*39:01:01:01 results in the novel allele, HLA‐ B*39:198. [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]

Breast cancer is the second most common malignancy in the world. Many studies have demonstrated the association between human leukocyte antigen (HLA) and cancer. This study discusses the relationships between female breast cancer occurrence in Guangxi and HLA-A and HLA-B allele polymorphisms, to provide a theoretical basis for defining the role of HLA gene polymorphism in breast cancer occurrence and the possible mechanism. Methods: Peripheral blood samples were collected from 88 female breast cancer patients and 81 healthy women from Guangxi. DNA was extracted, and HLA-A and HLA-B gene polymorphisms were identified by sequence-specific primer polymerase chain reaction (PCR-SSP). HLA-A and HLA-B genotypes were compared between the breast cancer patients and control women using the χ2 test. For HLA-A2, HLA-A3, HLA-A11, HLA-A24, HLA-A29, HLA-A30, HLA-A31, HLA-A33, and HLA-A74 gene frequencies, there were no significant differences between the breast cancer patient and control groups. Nineteen HLA-B alleles including HLA-B7, HLA-B13, HLA-B27, HLA-B38, HLA-B39, HLA-B46, HLA-B48, HLA-B50, HLA-B51, HLA-B52, HLA-B54, HLA-B55, HLA-B56, HLA-B58, HLA-B60, HLA-B61, HLA-B62, HLA-B71(70), and HLA-B75(15) were detected in the breast cancer patient and control groups. The HLA-B39 frequency was lower in the breast cancer group than in the control group. There were no significant differences in the gene frequencies of the remaining 18 alleles between the two groups. The HLA-B39 gene may be a protective genotype of female breast cancer in Guangxi, China, and no associations between the HLA-A alleles and female breast cancer in Guangxi were found. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has caused a health crisis worldwide; therefore, it is necessary to understand the factors related to its prognosis. In this study, we hypothesized that SARS-CoV-2-derived antigens presented by MHC class I may correlate with mortality in COVID-19 because they induce adaptive immune responses. Antigen coverage at the national level was inferred using country-specific HLA allele frequencies and relative predictions of binding antigens. We performed regression analysis between antigen coverage and the death rate due to COVID-19 across countries and found a negative correlation, although it was statistically significant only in HLA-B. This negative correlation was corroborated in multiple regression analysis with known risk factors, such as the prevalence of underlying disease. Furthermore, we analyzed antigen coverage in accordance with SARS-CoV-2 domains and identified a significant negative correlation when it was derived from the spike domain, which is reported to be favorable for COVID-19 prognosis. Taken together, the results indicate that the antigen coverage of SARS-CoV-2 specifically presented by HLA-B may act as a favorable factor when explaining COVID-19-induced mortality

The Major Histocompatibility Complex Class I-related chain A gene (MICA) is a highly polymorphic functional gene located close to the HLA - B locus. Certain MICA alleles have been related to inflammatory and autoimmune diseases while MICA antibodies have been implicated in organ allograft rejection or graft-versus-host disease (GVHD). The aim of this study was to identify the frequencies of MICA alleles and MICA ~ HLA-B haplotypes in the Greek population since, as far as we know, these data are still limited. DNA was obtained from 277 unrelated healthy Greek individuals of Caucasian origin, volunteer donors of blood stem cells. HLA - B * and MICA * genotyping was performed by reverse PCR-SSOP. A total of 18 MICA alleles were defined in the present study. The five most frequent alleles in the Greek population were MICA * 008 (24.6%), MICA * 009 (22.36%), MICA * 018 (16.03%), MICA * 002 (8.02%) and MICA * 004 (7.17%) which altogether account for 77.8% of all alleles. The most common MICA ~ HLA - B haplotypes were MICA * 018 ~ B*18 (12.5%) and MICA * 009 ~ B*51 (11.5%). The five most frequent MICA alleles in the Greek population were * 008 , * 009 , * 018 , * 002 , * 004. In other Caucasian populations, two of these alleles (* 008 , and * 004) were observed in similar frequencies. MICA * 002 was observed less frequently (8.02%) in the Greek population compared to other Caucasian groups (frequencies > 15%). Also, MICA * 009 and MICA * 018 had elevated frequencies (above 15%) whereas in other Caucasian populations they were found around 10% or less. These data may be important for the elucidation of the role that MICA polymorphisms play in organ and stem cell transplantation and to identify the relation of certain MICA with susceptibility to specific diseases. [ABSTRACT FROM AUTHOR]