Search

Introduction: Kidney dysfunction is a highly significant disease, both in the United Kingdom and globally. Many previous studies have reported associations between human leukocyte antigens (HLA) and renal function; this systematic review attempts to identify, summarize and appraise all published studies of these associations. Methods: A literature search was performed using Medline, Embase and Cochrane Central Register of Controlled Trials to identify papers whose keywords included each of the following concepts: HLA, renal failure and genetic association. A total of 245 papers were identified and assessed for eligibility; 35 of these were included in the final study. Results: A total of 95 HLA types and 14 three‐locus haplotypes were reported to be associated with either increased or decreased renal function. A number of these findings were replicated by independent studies that reported 16 types were protective against renal dysfunction and 15 types were associated with reduced renal function. A total of 20 HLA types were associated with both increased risk of renal disease and decreased risk by independent studies. Discussion: There is very little consensus on which HLA types have a protective or deleterious effect on renal function. Ethnicity may play a role, with HLA types possibly having different effects among different populations, and it is possible that the different primary diseases that lead to ESRD may have different HLA associations. Some of the studies may contain type I and type II errors caused by insufficient sample sizes, cohort selection and statistical methods. Although we have compiled a comprehensive list of published associations between renal function and HLA, in many cases, it is unclear which associations are reliable. Further studies are required to confirm or refute these findings. [ABSTRACT FROM AUTHOR]

HLA‐G allele frequencies were studied in Yucatán (Mexico) Maya Amerindians by a direct exon DNA sequencing technique. It is described that Mayas are probably one of the first populations together with Olmecs that populated Meso America and that important HLA genetic differences between Mexican and Guatemalan Mayas support that Maya languages were imposed to several neighbouring Amerindian groups. HLA‐G*01:01:02, HLA‐G*01:01:01 and HLA‐G*01:04:01 are the most frequent alleles in this population. It is remarkable that HLA‐G*01:05N allele was not found in the population in accordance with similar results found in another Amerindians. Also, protein allele HLA‐G*01:04 frequency is found not to differ to those found in another far or close living Amerindians in contrast to other World populations. It seems that while high HLA‐G*01:05N frequency is found in Iran and Middle East populations, probably where this allele appeared within an ancestral HLA‐A*19 group of alleles haplotype and it is maintained by unknown evolutionary forces, Amerindians do not have a high frequency because a founder effect or because required natural evolutionary forces do not exist in America. Finally, we believe useful to study HLA‐G evolution for its physiopathology understanding in addition to the many papers on statistics on HLA‐G and in vitro models that are yearly published. [ABSTRACT FROM AUTHOR]

Numerous published studies have investigated the relationship between the CD14−260C>T (rs2569190) polymorphism and the risk of myocardial infarction (MI). However, the results are still conflicting and inconclusive. Potentially eligible published articles were searched in four databases including PubMed, Web of Science, EMBASE and Chinese Biomedical Database (CBM). The odds ratio (OR) with its 95% confidence interval (CI) was used to estimate the strength of the associations. Thirteen papers including 17 case–control studies were included, reporting a total of 6,443 MI patients and 6,315 controls. A significant increase in overall MI susceptibility was identified in the homozygote model. In the subgroup analysis, with respect to the type of MI, a significantly increasing acute MI susceptibility was found in the homozygote model. In the subgroup analysis for ethnicity, a significant increased susceptibility was found in Asian populations in allele, homozygote, recessive and dominant models. However, no significant association was found among Caucasian populations. In conclusion, there may be a moderate association between the CD14−260C>T polymorphism and acute MI susceptibility. This association may be different between ethnicities with the CD14−260C>T polymorphism being a risk factor for myocardial infarction in Asian populations. [ABSTRACT FROM AUTHOR]

The article presents editorial policy regarding publication in the Immunogenetics community, while mentioning that reviewers to accept invitations and complete reviews in a timely manner, and also mentions the working of authors, reviewers and editorial board members.

Periodic fever syndromes (PFSs) are a family of clinical disorders, which are characterized by recurrent episodes of fever in the absence of microbial, autoimmune or malign conditions. Most common types of PFSs are associated with four genes: MEFV, MVK, TNFRSF1A and NLRP3. This paper aims to add new data to the genotype–phenotype association of MVK-, TNFRSF-1A- and NLRP3‐associated PFSs. A total number of 211 patients were evaluated. Two different approaches were used for the molecular genetic evaluation of MVK-, TNFRSF-1A- and NLRP3‐associated PFSs. For the first 147 patients, Sanger sequence analysis of selected exons of MVK, TNFRSF1A and NLRP3 genes was done. For subsequent 64 patients, targeted NGS panel analysis, covering all exons of MVK, TNFRSF1A and NLRP3 genes, was used. A total number of 48 variants were detected. The "variant detection rate in index patients" was higher in the NGS group than Sanger sequencing group (19% vs. 15,1%). For the variant positive patients, a detailed genotype–phenotype table was built. In PFSs, lack of correlation exists between genotype and phenotype in the general population and even within the families. In some cases, mutations behave differently and yield unexpected phenotypes. In this study, we discussed the clinical effects of eight different variants we have detected in the MVK, TNFRSF1A and NLRP3 genes. Four of them were previously identified in patients with PFS. The remaining four were not reported in patients with PFS. Thus, we had to interpret their clinical effects by analysing their frequencies and in silico analysis predictions. We suggest that new studies are needed to evaluate the effects of these variants more clearly. To be able to demonstrate a clearer genotype–phenotype relationship, all PFS‐related genes should be analysed together and the possibility of polygenic inheritance should be considered. [ABSTRACT FROM AUTHOR]

The FCGR locus is characterized by high polymorphism and sequence homology. In particular, the Ile232Thr polymorphism in the FCGR2B gene results in inaccurate genotyping in most published papers. The purpose of the study was to develop an accurate genotyping assay able to discriminate this polymorphism. [ABSTRACT FROM AUTHOR]

Cytotoxic T lymphocyte‐associated antigen‐4 (CTLA‐4) is involved in the regulation of immune responses mediated by T cells. This study aimed to explore the correlation between CTLA‐4 gene polymorphisms and the risk of gastric cancer (GC) in the Bai minority population of southwestern China. A total of 422 GC patients and 397 healthy controls (HC) were included in this case–control study. Four single nucleotide polymorphism sites of CTLA‐4 gene (rs231775, rs733618, rs16840252 and rs3087243) were selected and analysed. The results showed a significant difference in the rs733618 loci between GC and HC groups. The frequency of the rs733618 polymorphism 'TC' genotype was significantly lower in GC group compared to the HC group [odds ratio (OR), 95% confidence interval (CI):.47 (.35–.63), p <.001]. GC cases with dominant genetic model 'TC + CC' had a 47% reduced risk of GC [OR, 95%CI:.53 (.40–.71), p <.001]. Subgroup analyses revealed that the rs733618 'TC + CC' genotype was associated with a lower risk of GC in male patients [OR, 95%CI:.42 (.31–.58), p <.001], those aged ≤60 years old [OR, 95%CI:.27 (.18–.42), p <.001], non‐drinkers [OR, 95%CI:.21 (.13–.33), p <.001], non‐smokers [OR, 95%CI:.38 (.25–.57), p <.001] and individuals without Helicobacter pylori infection [OR, 95%CI:.16 (.10–.26), p <.001]. Further multivariated analyses indicated that individuals with the 'TC + CC' rs733618 genotype who were aged ≤60 years old [OR, 95%CI:.42 (.29–.83), p =.032] and had no H. pylori infection [OR, 95%CI:.35 (.28–.76), p =.018] were found to have a protective effect against GC. Additionally, soluble CTLA‐4 were significantly lower in GC patients with 'TC' and 'TC + CC' genotypes (all p <.05). Our findings suggest that the rs733618 polymorphism of CTLA‐4 gene may play a critical role in the prevention of GC. [ABSTRACT FROM AUTHOR]

B Alison Cleaton b , I Emma Burrows, Kimberley Robinson, Michael Richardson, Deborah Pritchard, Tracey Rees i I Welsh Blood Service, Ely Valley Road, Talbot Green, UK i Regular HLA antibody testing is undertaken for patients awaiting renal transplantation, using LABScreen™ HLA antibody assays. Three of these patients were HLA antibody negative and one patient was HLA antibody positive but HLA DSA negative. The HLA antibody results from samples prior to and following COVID-19 infection were analysed for changes in existing HLA antibody levels (increased Luminex Median Fluorescent Intensity (MFI) values), or expanded antibody profiles (increased cRF). P11 Improving the Laboratory Turnaround Time for Live Kidney Donor Transplant Compatibility T... B Deborah Pritchard b I Welsh Transplantation Laboratory, Pontyclun, UK i Immunological compatibility testing for potential live kidney donors and patients requires multiple tests on patient and donor samples (HLA typing, HLA antibody testing, crossmatch assessment). [Extracted from the article]

The inducible T‐cell costimulator (ICOS) may play an important role in adaptive immunity by regulating the interaction between T cells and antigen‐presenting cells. Disruption of this molecule can lead to autoimmune diseases, in particular systemic lupus erythematosus (SLE). In this study, we aimed to explore the possible association between ICOS gene polymorphisms and SLE as well as their influence on disease susceptibility and clinical outcomes. A further objective was to assess the potential impact of these polymorphisms on RNA expression. A case–control study, including 151 patients with SLE, and 291 unrelated healthy controls (HC) matched in gender, and geographical origin, was performed to genotype two polymorphisms located in the ICOS gene: rs11889031 (−693 G/A) and rs10932029 (IVS1 + 173 T/C); using the polymerase chain reaction (PCR)‐restriction fragment length polymorphism method. The different genotypes were validated by direct sequencing. The expression level of ICOS mRNA was assessed by quantitative PCR in peripheral blood mononuclear cells of SLE patients and HC. The results were analysed using Shesis and spss.20. Our results revealed a significant association between ICOS gene rs11889031 > CC genotype and SLE disease (codominant genetic model 1, (C/C vs. C/T), p =.001, odds ratio [OR] = 2.18 IC [1.36–3.49]); codominant genetic model 2, (C/C vs. T/T) p =.007, OR = 15.29 IC [1.97–118.5]); dominant genetic model, (C/C vs. C/T + T/T) p =.0001, OR = 2.44 IC [1.53–3.9]). Besides, there was a marginal association between rs11889031 > TT genotype and T allele with a protective role from SLE (recessive genetic model, p =.016, OR = 0.08 IC [0.01–0.63] and p = 7.6904E − 05, OR = 0.43 IC = [0.28–0.66], respectively). Moreover, statistical analysis indicated that the rs11889031 > CC genotype was linked with clinical and serological manifestations of SLE, including blood pressure, and anti‐SSA antibodies production in SLE patients. However, the ICOS gene rs10932029 polymorphism was not associated with susceptibility to SLE. On the other side, we did not note any effect of the two selected polymorphisms on the level of ICOS mRNA gene expression. The study showed a significant predisposing association of the ICOS rs11889031 > CC genotype with SLE, in contrast to a protective effect of rs11889031 > TT genotype in Tunisian patients. Our results suggest that ICOS rs11889031 may act as a risk factor for SLE and could be used as a genetic susceptibility biomarker. [ABSTRACT FROM AUTHOR]

Genetic polymorphisms of human leucocyte antigen (HLA)-DRB1, -DQA1 and -DQB1 among four main ethnic groups including Han (n = 70), Uyghur (n = 71), Kazakh (n = 52) and Hui (n = 40) subjects from Xinjiang Uyghur Autonomous Region were investigated using a polymerase chain reaction-sequence-based typing (PCR-SBT). In total, 32 HLA-DRB1 alleles, eight HLA-DQA1 alleles and 14 HLA-DQB1 alleles were identified. The most predominant HLA-DRB1, -DQA1 and -DQB1 alleles were DRB1*15:01 (12.50%), DQA1*01:02 (21.43%) and DQB1*03:01 (19.29%) in Han; DRB1*07:01 (18.48%), DQA1*05:01/03/05 (24.65%) and DQB1*02:01/02 (31.69%) in Uyghur; and DRB1*13:01 (13.64%), DQA1*05:01/03/05 (28.85%) and DQB1*02:01/02 (27.88%) in Kazakh, respectively. In Hui, DRB1*07:01, DRB1*11:01 and DRB1*14:01 were the most dominant alleles with the same frequency of 11.8%, while the predominant DQA1 and DQB1 alleles were DQA1*03:01/02/03 (23.75%) and DQB1*02:01/02 (16.25%), respectively. In addition, the most common two-locus haplotypes were DQA1*05:01/03/5-DQB1*03:01 (10.0%) in Han; DQA1*02:01-DQB1*02:01/02 (18.31%) in Uyghur; DQA1*05:01/03/05-DQB1*02:01/02 (15.38%) in Kazakh; and DQA1*03:01/02/03-DQB1*03:03 (11.25%) in Hui. The phylogenetic dendrograms constructed based on the allele frequencies of HLA-DRB1, -DQA1 and -DQB1 in 13 populations (e.g. Asian, Central Asian and European) revealed that the Han and Hui populations were clustered together and closest to Han population from China, while the Kazakh and Uyghur populations were closest to each other and two ethnic groups were clustered together with Central Asian and European populations., (© 2021 John Wiley & Sons Ltd.)

Contributions of candidate-gene associations studies and genome-wide association studies (GWAS) to identification of genetic variations associated with asthma. By focusing on unexpected and potentially confounding genetic variations, we can expand our understanding of the genetic factors associated with asthma susceptibility and identify new therapeutic targets for the treatment of this condition (Friedrich et al., [1]). Thank you for your comment on the publication 'Associations between interleukin 17A and 17F polymorphisms and asthma susceptibility: A meta-analysis' (Lee & Song, [2]). [Extracted from the article]

Owing to their role in inflammatory reactions and immunological responses as well as their chromosomal location, interleukin (IL) 17A and 17F are regarded as candidate causal genes associated with asthma. The aim of this study was to determine whether IL17 polymorphisms are associated with susceptibility to asthma. We used the PubMed/Medline and Embase databases to search for studies reporting IL17 polymorphisms in patients with asthma and healthy controls. Meta‐analyses were conducted to determine the associations between IL17A rs8193036 (−737C/T), rs2275913 (−197G/A), rs3819024 (A/G), rs3748067 (C/T), and rs4711998 (A/G) and IL17F rs763780 (7488A/G), rs2397084 (T/C), rs1889570 (C/T), rs11465553 (G/A), and rs1266828 (T/C) polymorphisms and asthma susceptibility. A total of 20 studies were included in this meta‐analysis. Our results revealed the IL17A rs8193036 CC genotype was associated with asthma susceptibility (odds ratio [OR] = 1.490, 95% confidence interval [CI] = 1.027–2.161, p =.036). However, stratification by ethnicity indicated no association between this polymorphism and asthma in European and Asian subjects. Furthermore, no association was found between this polymorphism and asthma using the allele contrast, dominant or homozygous contrast models. No evidence of an association was found between any of the other IL17A and IL17F polymorphisms and asthma susceptibility in this meta‐analysis. This meta‐analysis showed that, among the studied polymorphisms, only the CC genotype of IL17A rs8193036 is associated with asthma susceptibility. [ABSTRACT FROM AUTHOR]

HLA‐DPA1 intralocus recombination between DPA1*04:01:01:03 and DPA1*01:03:01:27, or closely related other alleles, results in a novel allele HLA‐DPA1*01:03:43. [ABSTRACT FROM AUTHOR]

Coronavirus disease‐2019 (COVID‐19) is pro‐inflammatory disorder characterized by acute respiratory distress syndrome. Interleukin‐6, a cytokine secreted by macrophages, which mediates an inflammatory response, is frequently increased and associated with the severity in COVID‐19 patients. The differential expression of IL6 cytokine in COVID‐19 patients may be associated with the presence of single nucleotide polymorphisms (SNPs) in regulatory region of cytokine genes. The aim of this study is to investigate the role of two promoter polymorphisms of the IL6 gene (–597G > A and –174G > C) with the severity of COVID‐19. The study included 242 patients, out of which 97 patients with severe symptoms and 145 patients with mild symptoms of COVID‐19. Genotyping of two selected SNPs, rs1800795 (–174G > C) and rs1800797 (–597G > A) of promoter region of IL6 gene, was performed by polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP). In our study, individuals with GC genotypes of IL6 (–174G > C) polymorphism showed significantly higher risk of severity [adjusted odds (OR) 3.86, p <.001] but we did not observe any association of COVID‐19 severity with rs1800797 (–597G > A) polymorphism. The COVID‐19 severity was significantly higher in individuals having 'C' allele of IL6 (–174G > C) polymorphism (p =.014). Linkage disequilibrium between rs1800795 (–174G > C) and rs1800797 (–597G > A) showed that individuals having AC* haplotype significantly association with COVID‐19 severity (p =.034). Our results suggest that 'C' allele of rs1800795 (–174G > C) polymorphism of IL6 may be the risk allele for severity of COVID‐19 in North Indian population. [ABSTRACT FROM AUTHOR]

Human leucocyte antigen (HLA) alleles may generate antibodies that are undetectable by routine single-antigen beads (SABs) assays if their unique epitopes are unrepresented. We aimed to describe the prevalence and explore the potential impact of unrepresented HLA alleles in standard SAB kits in our cohort. All individuals who had undergone two-field HLA typing (HLA-A/B/C/DRB1/DQA1/-DQB1/-DPA1/-DPB1) from February 2021 to July 2023 were included. Two-field HLA-DRB3/4/5 typing was imputed. Each unrepresented allele was compared with the most similar represented allele in the standard LABScreen, LABScreen ExPlex (One Lambda) and the LIFECODES (Immucor) SAB kits. Differences in eplet expression (HLA Eplet Registry) were identified. Differences in three-dimensional molecular structures were visualized using generated models (SWISS-MODEL). Two-field HLA typing was performed for 116 individuals. Overall, 16.7% of all HLA alleles, found in 36.2% of individuals, were unrepresented by all SAB test kits. Four eplets, found in 12.9% of individuals, were unrepresented in at least 1 SAB kit. Non-Chinese individuals were more likely to have unrepresented HLA alleles and eplets than Chinese individuals. There were differences in HLA allele and eplet representation amongst the different SAB test kits. Use of supplementary SAB test kits may improve HLA allele and eplet representation. Although some HLA alleles were unrepresented, most epitopes were represented in current SAB kits. However, some unrepresented alleles may contain epitopes which may generate undetectable antibodies. Further studies may be needed to investigate the potential clinical impact of these unrepresented alleles and eplets, especially in certain ethnic populations or at-risk individuals., (© 2023 John Wiley & Sons Ltd.)

Haplotyping or determination of genetic phase has always played a pivotal role in MHC (HLA studies) both in helping to understand inheritance patterns in diseases such as type 1 diabetes (T1D) and in ensuring better matching in transplantation scenarios such as haematopoietic stem cell transplantation (HSCT), using donors genetically related to the patient. In recent years the need to establish genetic phase in a number of clinical scenarios has become apparent. These include: Genetic phasing for hematopoietic stem cell transplants using unrelated donors, where the HLA haplotypes are not known but where haplotype‐matched recipients fare better clinically than allele matched, but haplotype mismatched patients.The use of checkpoint inhibitors is one of the most innovative and exciting developments in cancer treatment in years. An example is the use of the monoclonal ipilimumab to block the CTLA‐4 receptor which is known to contain polymorphic sites. Until the phase of these polymorphisms is known it will not be possible to determine how effectively this monoclonal will perform in individual patients.The role of miRNA single strand molecules and their effect on gene expression. Thousands of non‐coding genes have been identified and have been shown to be polymorphic, as have their target genes. Genetic phasing of polymorphism both in the miRNA source genes and their targets is clearly a fertile area of researchIn areas such a drug metabolism where the polymorphic family of CYP genes is responsible for the metabolism of the majority of prescription drugs, determining phase of SNPs is critical to understanding drug metabolism and efficacy.In multigenic disease studies combinations of single nucleotide polymorphisms (SNPs) in participating genes require accurate phasing in order to fully appreciate their role in the disease process. In addition, the level of expression of genes (point 3) is also important in understanding disease processes at the functional level.This review outlines the techniques that are currently available for approximating phase and discusses the clinical relevance of establishing genetic phase in areas of clinical medicine outlined in points 1–3. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "The association of 330 interleukin-2 gene polymorphism and hla-dr15 allele in iranian patients with multiple sclerosis" by A. Sayad.

A review of the British Society for Histocompatibility and Immunogenetics (BSHI) Guideline 'HLA matching and donor selection for haematopoietic progenitor cell transplantation' published in 2016 was undertaken by a BSHI appointed writing committee. Literature searches were performed and the data extracted were presented as recommendations according to the GRADE nomenclature. [ABSTRACT FROM AUTHOR]

The development of donor‐specific antibodies (DSAs) is a major complication in transplantation, which is associated with inferior graft survival, impaired quality of life, and increased healthcare costs. DSA develop upon recognition of nonself HLA by the recipient's immune system. HLA molecules contain epitopes, which are the surface regions of HLA molecules recognized by antibodies. HLAMatchmaker is an algorithm for assessing donor:recipient HLA compatibility at the level of structurally defined HLA targets called eplets. The consideration of eplets, rather than the whole HLA molecule, could offer some advantages when classifying the immune risk associated with particular donor:recipient pairs. Assessing compatibility at the level of HLA eplets could decrease misclassification of post‐transplant immune risk by improving specificity, when antibodies are confirmed to be directed against donor eplets missing from the recipient's repertoire of eplets. Consideration of eplets may also increase the sensitivity of immune risk assessment, when identifying mismatched eplets that could give rise to new, not previously detected, donor‐specific antibodies post‐transplant. Eplet matching can serve as a rational strategy for immune risk mitigation. Herein, we review the evolution of HLA (in) compatibility assessment for organ allocation. We outline challenges in the implementation of eplet‐based donor:recipient matching, including unavailability of allele‐level donor genotypes for 11 HLA loci at the time of organ allocation and difficulty in assessing the hierarchy of immune risk associated with particular HLA eplet mismatches. Opportunities to address some of the current shortcomings of donor genotyping and HLAMatchmaker are also discussed. While there is a demonstrated benefit in the application of HLAMatchmaker for donor: recipient HLA (in)compatibility assessment, evolving long‐read genotyping methods, compilation of large data sets with allele‐level genotypes, and standardization of methods to verify eplets as determinants of immune‐mediated injuries are required before HLA eplet matching is implemented in organ allocation to improve upon transplant outcomes. [ABSTRACT FROM AUTHOR]

Background: The published evidences on the correlations of toll‐like receptor 4 (TLR4) and TLR9 gene polymorphisms and ankylosing spondylitis (AS) were conflicting. The purpose of this study was to investigate whether TLR4 and TLR9 gene polymorphisms conferred susceptibility to AS through a meta‐analysis approach. Methods: Databases of PubMed, Web of Science, EMBASE, Cochrane Library, CNKI and Wanfang were retrieved for relevant publications up to 20 June 2020. Study quality was assessed based on Newcastle‐Ottawa scale (NOS). Odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to judge the associations. Results: Totally, 13 articles with 3,055 AS cases and 4,238 controls were incorporated into this meta‐analysis, and four most widely reported polymorphisms (TLR4‐rs4986790, TLR4‐rs4986791, TLR9‐rs55704465 and TLR9‐rs187084) were analysed. All included studies were in high quality. The pooled data did not support any significant association between the four studied polymorphisms and AS susceptibility. Conclusions: The present meta‐analysis suggests there is no significant association between TLR4‐rs4986790, TLR4‐rs4986791, TLR9‐rs55704465 and TLR9‐rs187084 polymorphisms and AS. [ABSTRACT FROM AUTHOR]

HLA donor‐specific antibodies developed de novo after transplant remain a major cause of chronic allograft dysfunction. Our study main purpose was to determine whether HLA MM, assessed traditionally and by HLA total and AbVer eplet mismatch load (EptMM and EpvMM) assessed with HLAMatchMaker, had impact on dnDSA development after living donor kidney transplantation (LDKT). We retrospectively analysed a cohort of 96 LDKT between 2008 and 2017 performed in Hospital Santo António. Seven patients developed dnDSA‐II and EpvMM and EptMM were greater in dnDSA‐II group compared to the no dnDSA‐II (18.0 ± 8.7 versus 9.9 ± 7.9, p =.041 and 41.3 ± 18.9 versus 23.1 ± 16.7, p =.018), which is not observed for AgMM (2.29 versus 1.56; p =.09). In a multivariate analysis, we found that preformed DSA (HR = 7.983; p =.023), living unrelated donors (HR = 8.052; p =.024) and retransplantation (HR = 14.393; p =.009) were predictors for dnDSA‐II (AUC = 0.801; 0.622–0.981). HLA‐II EpvMM (HR = 1.105; p =.028; AUC = 0.856) showed to be a superior predictor of dnDSA‐II, when compared to AgMM (HR = 1.740; p =.113; AUC = 0.783), when adjusted for these clinical variables. Graft survival was significantly lower within dnDSA‐II patient group (36% versus 88%, p <.001). HLA molecular mismatch analysis is extremely important to minimize risk for HLA‐II dnDSA development improving outcome and increasing chance of retransplant lowering allosensitization. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV)‐infected individuals may have a faster progression of liver fibrosis, cirrhosis and hepatocellular carcinoma (HCC) development when influenced by host, viral and environmental factors. Hepatitis C virus disease progression is also associated with genetic variants of specific killer cell immunoglobulin‐like receptors (KIRs) and genes of the major histocompatibility complex (MHC). The aim of the present study was to correlate clinical, virologic and biochemical parameters and to evaluate the possible influence of KIR genes and their HLA class I ligands in patients infected with hepatitis C virus. The present study analysed a total of 127 chronic HCV‐infected patients for various biochemical and genetics factors that can influence disease progression and prognosis. Liver function parameters such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma‐glutamyl transferase (GGT), direct bilirubin (DB), alpha‐fetoprotein (AFP), HCV RNA levels and fibrosis indices were analysed using well‐established biochemical methods. At the same time, KIR and HLA genotyping was performed using a polymerase chain reaction sequence‐specific primer technique. Analysis of HLA class I and HLA ligands revealed that HLA‐C*12:02 and HLA‐A3 and HLA‐A11 were positively associated with the F3‐F4 fibrosis group (p =.026; OR = 8.717, CI = 1.040–73.077; respectively, p =.047; OR = 2.187; 95% CI = 1.066–4.486). KIR2DL2‐positive patients had high median levels of AST after treatment and direct bilirubin levels when compared to KIR2DL2‐negative patients (p =.013, respectively, p =.028). KIR2DL2/KIR2DL2‐C1C1 genotype was associated with increased AST, ALT and GGT levels. A higher GGT level was also observed in KIR2DS2‐C1‐positive patients when compared to KIR2DS2‐C1‐negative patients. The present research demonstrates several links between specific clinical, virologic and biochemical parameters and the expression of KIR genes and their HLA ligands in HCV‐infected patients. These connections should be taken into account when considering disease development and treatment. [ABSTRACT FROM AUTHOR]

B and T lymphocyte attenuator (BTLA) is an immune‐inhibitory receptor that negatively regulates the lymphocyte activation. A few studies have been devoted to the relationship between BTLA gene variations and cancer's risk. It has been essentially demonstrated to be involved in increasing cancer risk in chronic lymphocyte leukaemia, renal cell carcinoma, breast and colorectal cancer predispositions in Asian population. The aim of this study was to evaluate the association between BTLA gene polymorphisms and the risk of lung cancer in the Tunisian population. In a case–control study, three BTLA single‐nucleotide polymorphism (SNP): rs1982809 (A > G), rs9288952 (G > A) and rs9288953(C > T) were genotyped with the use of TaqMan probes in 169 lung cancer patients and in 300 controls. The rs1982809 SNP was significantly associated with an increased risk of lung cancer compared with controls in codominant and dominant models. The heterozygous rs1982809‐AG genotype carriers had a higher risk of developing lung cancer when compared to AA genotype carriers in Tunisian population (OR (95%CI) = 1.63 (1.09–2.42), p =.01]. The AG genotype is an important risk factor associated with lymphatic invasion (OR = 3.71) and large‐sized lung tumour (OR = 1.80). It is also a risk factor for the development of an adenocarcinoma subtype (OR = 2.08). However, the BTLA rs9288953 and rs9288952 SNPs were not associated with susceptibility for lung cancer (p >.05). Haplotype comparison did not show any significant association in our research. For the survival analysis, there was no impact of BTLA SNPs on the mortality risk associated to lung cancer in Tunisian patients. The current study is the first to demonstrate an association between BTLA rs1982809 polymorphism and an increased lung cancer risk in the Tunisian population. [ABSTRACT FROM AUTHOR]

We analysed data from 80 patients who tested positive for SARS‐CoV‐2 RNA who had previously been HLA typed to support transplantation. Data were combined from two adjacent centres in Manchester and Leeds to achieve a sufficient number for early analysis. HLA frequencies observed were compared against two control populations: first, against published frequencies in a UK deceased donor population (n = 10,000) representing the target population of the virus, and second, using a cohort of individuals from the combined transplant waiting lists of both centres (n = 308), representing a comparator group of unaffected individuals of the same demographic. We report a significant HLA association with HLA‐ DQB1*06 (53% vs. 36%; p <.012; OR 1.96; 95% CI 1.94–3.22) and infection. A bias towards an increased representation of HLA‐A*26, HLA‐DRB1*15, HLA‐DRB1*10 and DRB1*11 was also noted but these were either only significant using the UK donor controls, or did not remain significant after correction for multiple tests. Likewise, HLA‐A*02, HLA‐B*44 and HLA‐C*05 may exert a protective effect, but these associations did not remain significant after correction for multiple tests. This is relevant information for the clinical management of patients in the setting of the current SARS‐CoV‐2 pandemic and potentially in risk‐assessing staff interactions with infected patients. [ABSTRACT FROM AUTHOR]

Susceptibility to viral infection, development of immunity, response to treatment and patient clinical outcomes are all under the control of heritable factors in the host. In the context of the current SARS‐Cov‐2 pandemic, this review considers existing immunogenetic knowledge of virus‐immune system interactions. A major focus is to highlight areas in which work is required in order to improve understanding of antiviral immune responses and to move towards improved patient management. [ABSTRACT FROM AUTHOR]

Autoimmune thyroid diseases (AITD) including Graves' disease (GD) and Hashimoto's thyroiditis (HT) are complex genetic diseases. Th2 cytokines act on the development of AITD. This study was conducted on Tunisian patients with AITD to investigate the association of Th2 cytokine gene polymorphisms and haplotype combination with GD or HT risk. A total of 156 controls, 160 patients with HT and 88 patients with GD were genotyped for IL‐4 rs2243250, IL‐5 rs2069812, IL‐6 rs1800796 and IL‐13 rs1800925 polymorphisms by PCR‐RFLP. The AITD risk was assessed by a logistic regression analysis using the SNP stats statistical program. False‐positive report probability (FPRP) was estimated to evaluate significant findings. IL‐13 rs1800925 was associated with GD, after adjustment for age and gender, in codominant, dominant and allele genetic models (p =.0072; p =.0018; p =.012, respectively). Significant association of the IL‐6 rs1800796C/G genotype with GD was also detected (p =.025). Furthermore, increased risk of HT was still found for IL‐13 rs1800925T allele (p =.039, OR = 1.39) and for IL‐4 rs2243250T/T genotype both in codominant (p =.033, OR = 2.59) and recessive (p =.011, OR = 2.73) models after adjustment for age and gender. Interestingly, haplotype analysis performed on the IL‐4, IL‐5 and IL‐13 genes revealed a high risk of HT with CTT haplotype (p =.008, OR = 2.12). However, the CCT haplotype is a protective factor (OR = 0.36). Patients carrying the CT haplotype with only one minor allele had a moderate risk of HT (OR = 1.56). The FPRP analysis showed that the association of IL‐13 rs1800925 polymorphism with GD and HT and the association of CTT haplotype with HT were noteworthy. In conclusion, the IL‐4, IL‐5, IL‐6 and IL‐13 polymorphism may play a role in susceptibility to GD and HT in the Tunisian population. Furthermore, gene–gene interaction between the IL‐4, IL‐5 and IL‐13 significantly increases the risk of AITD. Further studies with larger numbers of individuals are needed to confirm the results. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is referred to as an organ‐specific T‐cell‐mediated autoimmune disease of the central nervous system (CNS). Different genetic and environmental factors increase the risk of developing MS. In recent years, microchimerism (Mc) has been widely studied in autoimmune diseases, although the exact role of this phenomenon in human health is not known well. Microchimerism is the low level presence of DNA or cells from one individual into the tissue or circulation of another individual. In the current study, we evaluated the association of fetal microchimerism (FMc) with MS in Isfahan province. In this study, we enrolled 68 women in four groups. Two groups were MS patients with or without a pregnancy for a son, and the other two groups were MS‐negative patients with or without a pregnancy for a son. The presence of the male genome assessed and compared in these groups. Four millilitres of peripheral blood were collected from all subjects in the tube containing EDTA and DNA was extracted. Real‐time PCR assay was used for the DAZ (deleted in azoospermia) region Yq 11.23 as a marker for male microchimerism in all subjects. Our results showed that the percentage of DAZ (male genome)‐positive women was significantly higher in MS‐positive women given birth to a son in comparison with the other three groups. Our results also revealed no significant correlation between the percentage of DAZ‐positive women and Expanded Disability Status Scale (EDSS) score and age of onset in the patients' group. For future studies, we suggest enrolling subjects who MS diagnosis occurred before and after pregnancy with a son. Comparing FMc in these two groups might provide a better understanding of the possible role of FMc in later development of MS. [ABSTRACT FROM AUTHOR]

Endometrial cancer (EC) is one of the most common malignant tumours of the female genital tract, and it has become a serious malignant disease of the female genital tract in China. Existing researches have revealed the association between polymorphisms of IL‐1A and several gynaecological diseases. In this research, we analysed the association between IL‐1A gene polymorphisms and endometrial cancer susceptibility in Chinese female population. A total of 81 patients and 198 healthy people were selected. Odds ratio (OR) and 95% confidence intervals (CIs) were calculated using unconditional logistic regression. Genetic models and analyses showed that IL‐1A rs3783550 TT and rs3783546 CC increased the risk of endometrial cancer under the recessive model, respectively (rs3783550: OR = 2.80, 95%CI: 1.32–5.92, p =.008; rs3783546: OR = 2.79, 95%CI: 1.32–5.89, p =.008). In the recessive model, we also found that both IL‐1A rs1609682 and IL‐1A rs3783521 increased the risk of endometrial cancer, respectively (rs1609682: OR = 2.79, 95%CI: 1.32–5.89, p =.0081; rs3783521: OR = 2.80, 95%CI: 1.32–5.92, p =.008). Haplotype analysis was performed that did not reveal any significant results. In summary, IL‐1A rs3783550, rs3783546, rs1609682 and rs3783521 polymorphisms may be associated with an increased risk of endometrial cancer in Chinese female populations. [ABSTRACT FROM AUTHOR]

Since the beginning of life, every multicellular organism appeared to have a complex innate immune system although the adaptive immune system, centred on lymphocytes bearing antigen receptors generated by somatic recombination, arose in jawed fish approximately 500 million years ago. The major histocompatibility complex MHC, named the Human leucocyte antigen (HLA) system in humans, represents a vital function structure in the organism by presenting pathogen‐derived peptides to T cells as the main initial step of the adaptive immune response. The huge level of polymorphism observed in HLA genes definitely reflects selection, favouring heterozygosity at the individual or population level, in a pathogen‐rich environment, although many are located in introns or in exons that do not code for the antigen‐biding site of the HLA. Over the past three decades, the extent of allelic diversity at HLA loci has been well characterized using high‐resolution HLA‐DNA typing and the number of new HLA alleles, produced through next‐generation sequencing methods, is even more rapidly increasing. The level of the HLA system polymorphism represents an obstacle to the search of potential compatible donors for patients affected by haematological disease proposed for a hematopoietic stem cell transplant (HSCT). Data reported in literature clearly show that antigenic and/or allelic mismatches between related or unrelated donors and patients influences the successful HSCT outcome. However, the recent development of the new transplant strategy based on the choice of haploidentical donors for HSCT is questioning the role of HLA compatibility, since the great HLA disparities present do not worsen the overall clinical outcome. Nowadays, NGS has contributed to define at allelic levels the HLA polymorphism and solve potential ambiguities. However, HLA functions and tissue typing probably need to be further investigated in the next future, to understand the reasons why in haploidentical transplants the presence of a whole mismatch haplotype between donors and recipients, both the survival rate and the incidence of acute GvHD or graft rejection are similar to those reported for unrelated HSCTs. [ABSTRACT FROM AUTHOR]

This short review will be concerned with the literature that has developed connected with the immunogenetic and tissue compatibility aspects of hand transplantation and will also draw on connected work in the more general area of vascularized composite allotransplantation (VCA) which includes face, abdominal wall uterus and larynx. [ABSTRACT FROM AUTHOR]

The UK hand transplantation programme is hosted by the Department of Plastic and Reconstructive Surgery at Leeds Teaching Hospitals under the leadership of Professor Simon Kay. Since programme launch in 2013, ten procedures in six individuals have been performed involving unilateral or bilateral transplants. The multi‐disciplinary team that delivers the programme includes the transplant immunology service. The laboratory experience in programme support is reported here. [ABSTRACT FROM AUTHOR]

HLA gene expression has an important role in the autoimmune disease predisposition. We investigated the mRNA expression profile of the risk alleles HLA‐DRB1*15 and HLA‐DRB1*13 in a cohort of subjects both multiple sclerosis (MS) patients and healthy controls. Moreover, we explored the expression of the allele HLA‐DRB1*11 that is very frequent in our cohort from southern Italy. We found that the expression of MS‐associated alleles in heterozygous MS patients was always higher than the nonassociated alleles. The differential risk allele expression occurred also in nonaffected subjects, though with a lower increment compared to MS patients. [ABSTRACT FROM AUTHOR]

The detection and semiquantitative measurement of circulating human leucocyte antigen (HLA)‐specific antibodies is essential for the management of patients before and after transplantation. In addition, the pretransplant cross‐match to assess the reactivity of recipient HLA antibody against donor lymphocytes has long been the gold standard to prevent hyperacute rejection. Whilst both of these tests assume that recipient HLA‐specific antibody is the only variable in the assessment of transplant risk, this is not the case. Transplant immunologists recognize that some HLA antigens are expressed at levels a magnitude lower than others (e.g., HLA‐C, HLA‐DQ), but within loci, and between different cell types there are many factors that influence HLA expression in both resting and activated cells. HLA is not usually expressed without the specific promoter proteins NLRC5, for HLA class I, and CIITA, for class II. The quantity of HLA protein production is then affected by factors including promoter region polymorphisms, alternative exon splice sites, methylation and microRNA‐directed degradation. Different loci are influenced by multiple combinations of these control mechanisms making prediction of HLA regulation difficult, but an ability to measure the cellular expression of each HLA antigen, in conjunction with knowledge of circulating HLA‐specific antibody, would lead to a more informed algorithm to assess transplant risk. [ABSTRACT FROM AUTHOR]

Polymorphic Alu insertions (POALINs) are found throughout the human genome and have been used in various studies to infer geographic origin of human populations. The main aim of this study was to determine the allele and haplotype frequencies of five POALINs, AluHF, AluHG, AluHJ, AluTF and AluMICB, within the major histocompatibility complex (MHC) class I region of 95 UAE Arabs, and correlate their frequencies to those of the HLA‐A, HLA‐C and HLA‐B class I allele lineages. Evolutionary relationships between the POALINs of the Arabs and those previously studied in populations of African, Asian and European descent were compared. At each of the five Alu loci (AluHF, AluHG, AluHJ, AluTF and AluMICB), Alu insertion was designated as Alu(locus)*02 and absence was Alu(locus)*01. The AluHG insertion (AluHG*02) had the highest frequency (0.332), followed by AluHF*02 (0.300), AluHJ*02 (0.263), AluMICB*02 (0.111) and AluTF*02 (0.058). Of the 270 Alu‐HLA haplotypes pairs in the UAE Arabs, 110 had no Alu insertion, and 54 had an Alu insertion at >50% per haplotype. An Alu insertion >75% per haplotype was found between AluMICB*02 and HLA‐B*14, HLA‐B*22, HLA‐B*44, HLA‐B*55, HLA‐B*57 and HLA‐B*73, and with HLA‐C*01 and HLA‐C*18; AluHJ*02 with HLA‐A*01, HLA‐A*19, HLA‐A*24 and HLA‐A*32; AluHG*02 with HLA‐A*02 and HLA‐B*18; and AluHF*02 with HLA‐A*10. The genotyped allele and haplotype frequencies of the MHC POALINs in UAE Arabs were compared with the results of 30 previously published Asian, European, American and African populations. Phylogenetic and multidimensional scaling (MDS) analysis of the relative MHC POALINs allele and haplotype frequencies revealed that the UAE Arabs have a similar lineage to Caucasians and the most distant genetic relationship to the Waorani native American population of Ecuador. The structure of both the phylogenetic tree and the MDS analysis supports the Out of Africa theory of human evolution. The nature of the clusters suggests the Arabian Middle East represents a crossroads from which human populations migrated towards Asia in the east and Europe to the north‐west. [ABSTRACT FROM AUTHOR]

LILR and KIR receptors recognize HLA‐B27 and may influence immune response in ankylosing spondylitis (AS) development. Purpose of the study was to analyse LILRB1/LILRA3 polymorphisms in AS. We observed a possible protective effect of the T allele of LILRB1 rs1061680:T>C and no association with insertion/deletion polymorphisms of LILRA3 with AS. [ABSTRACT FROM AUTHOR]

Despite the apparent simplicity of the body organization of echinoderms, their immune system is competent to perform a complex innate immune response, which is far from being well understood. The echinoderms represent the most advanced invertebrates that form a bridge with the primitive chordates. In fact, they possess numerous receptors and effectors that are used to obtain a fast immune response. After an infection, the humoral and cellular immune response determines a network in which the main protagonists are membrane and endosomal receptors. The recognition of nonself molecules by specific membrane receptors triggers the immune response, stimulating consecutive intracellular events. We have previously shown how the polyinosinic–polycytidylic acid (polyI:C) that mimics a viral infection is able to induce an immune response in the sea urchin Paracentrotus lividus immune cells. It activates a specific membrane receptor belonging to the Toll‐like receptor (TLR) family. Here, we show the activated expression pattern of some genes involved in the downstream cascade of TLR signalling pathway, such as Pl‐Tbk and Pl‐Irf, whose partial sequence was isolated from P. lividus immune cells. Their mRNA expression increases consequentially to the polyI:C stimulation and in a temporal way. In addition, we analysed the expression of Pl‐NF‐kB and we found that its upregulation was time‐dependent, preceding Pl‐Tbk and Pl‐Irf increase. Protein analysis showed that also some cytokine (TNF‐α and IL‐1α) expression increased after polyI:C insult. Therefore, the purpose of this study was to discover the molecular mechanisms of the innate defence strategies, similarly to vertebrates, implemented by the sea urchins in order to cope with viral infection challenge. [ABSTRACT FROM AUTHOR]

Knowledge on blood group phenotypes is of key importance in clinical practice. It used in blood transfusion practice to determine the direction of recruitment of voluntary donors as required for each population within a country, and for disease association and population genetics studies. This study aimed at reporting the frequency of ABO and Rhesus (Rh) groups in the population of the Greater‐Accra region of Ghana and amongst their various ethnic groups. A retrospective study in 11 main hospitals within the region was done. Data collected provided information on the blood group status of persons (both blood donors and recipients) who visited the selected hospitals. Medical records used were within the years 2012–2017. A total of 42,317 (26,802 males and 15,515 females) data were retrieved and analysed. The frequencies of the blood groups O, A, B and AB were 50.0%, 24.3%, 20.7% and 5.0%, respectively. Rhesus‐positive to negative ratio was 93.2%/6.2%. Frequencies of blood group O was highest (49.1%–53.6%) in all ethnic groups. The second most dominant blood group was B (24.2%–25.4%) in the Ga‐Adamgbe, Akan and Ewe ethnic groups, whilst blood group A (25.0%–26.9%) was the second most dominant in the Northerners and non‐Ghanaians. Blood group distribution amongst gender and different age groups showed no significant differences but followed the same pattern for the general population. The study provides data on the ethnic distribution and frequency of ABO and Rhesus blood groupings in the Greater‐Accra region of Ghana. It also informs the need for blood banks in the region to increase the proportion of stockpiled Rhesus‐positive blood groups especially for O, B and A that may be high in demand. [ABSTRACT FROM AUTHOR]

The importance of HLA alleles in the process of haematopoietic stem cell transplantation, especially the process of unrelated donor search, is enormous. Macedonian Bone Marrow Donor Registry was established in 2010 and has registered volunteer donors from different nationalities that live in the Republic of Macedonia. The aim of this study was to determine the HLA allele and haplotype frequencies of the volunteer donors from the Macedonian Bone Marrow Donor Registry and to compare this results with the Macedonians from a family study. We analyzed 1,541 donors, with different nationalities, Macedonian, Albanian and Macedonian Muslims that were most numerous in MBMDR, and typed them for HLA‐A, ‐B, ‐C, ‐DRB1, whereas Macedonian also for HLA‐DQA1 and HLA‐DQB1 by SSO method (One Lambda, CA, USA). The most frequent alleles in Macedonians were HLA‐A*02, 01, 24; HLA‐B*35, 18, 51; HLA‐C*07, 04, 12; HLA‐DRB1*11, 16, 13; HLA‐DQA1*01, 05 and HLA‐DQB1*05, 03, 06; in Albanians they were HLA‐A*02, 24,01; HLA‐B*51, 18, 35; HLA‐C*07, 04, 12, HLA‐DRB1*11, 13,16; and in Macedonian Muslims they were HLA‐A*02, 01, 24; HLA‐B*18, 51, 35, HLA‐C*07, 04, 02 and HLA‐DRB1*11, 16, 14. The most common haplotype in Macedonian was HLA‐A*01‐B*08‐C*07‐DRB1*03, whilst in Albanian and Macedonian Muslims HLA‐A*02‐B*18‐C*07‐DRB1*11. The comparison of the HLA allele groups between Macedonian from MBMDR and family study showed similar distribution. This study confirmed the close relationship between the populations that live in the Balkan Peninsula. [ABSTRACT FROM AUTHOR]

Loss of heterozygosity is considered to be the most common type of tumour‐specific somatic mutation of the human leucocyte antigens (HLA) genes in patients with haematological malignancies. Nevertheless, subtle DNA sequence changes, namely short insertions/deletions, may also abolish the expression of HLA molecules and interfere with routine HLA typing. Two male patients with acute myelogenous leukaemia (AML) were indicated for the search of a suitable donor for allogeneic haematopoietic stem cell transplantation (aHSCT). The patients and their relatives were initially HLA typed by serological and DNA techniques at a low‐resolution level. The HLA high‐resolution (HR) type was obtained by means of sequencing‐based typing (SBT). In both cases, anomalous frameshifts in the sequence were observed in the HLA‐B gene, namely in exon 3 (Case 1, heterozygous deletion of two bases) and exon 4 (Case 2, heterozygous insertion of two bases). In the second case, the insertion variant was associated with a loss of HLA‐B8 expression. To reveal whether these sequence patterns may be caused by somatic mutations in the malignant cells, blood sample in remission (Case 1) and buccal swab sample (Case 2) were collected from the patients. In an important manner, the SBT in these germline samples revealed common HLA‐B*07:02,*15:01 (Case 1) and HLA‐B*08:01,*35:02 (Case 2) types with no evidence for the sequence alteration observed in the initial samples. In conclusion, the insertion/deletion sequence variants of the HLA‐B gene in two patients were limited to the initial blood samples with a substantial proportion of AML cells and thus may be attributed to the somatic mutation in the malignant cells. HLA somatic mutations should be taken into account in patients with haematological malignancies to prevent HLA mistyping and inappropriate selection of an aHSCT donor. [ABSTRACT FROM AUTHOR]

Abstract: The distribution of human leucocyte antigen (HLA) allele and haplotype varied among different ethnic populations. In this study, we investigated the allele and haplotype frequencies of HLA‐A, HLA‐B and HLA‐DRB1 loci in the Nanning Han population who live in Guangxi province of China. We identified 26 HLA‐A, 56 HLA‐B and 31 HLA‐DRB1 alleles in 562 Nanning individuals of Han ethnic group by sequence‐based typing method. Of these, the three most common alleles in HLA‐A, HLA‐B and HLA‐DRB1 loci, respectively, were A*11:01 (32.12%), A*02:07 (12.54%), A*24:02 (12.01%); B*46:01 (14.41%), B*15:02 (13.61%), B*40:01 (11.48%); DRB1*15:01 (14.15%), DRB1*16:02 (11.57%) and DRB1*12:02 (10.14%). With the exception of HLA‐DRB1, the p values of the HLA‐A and HLA‐B loci showed that the HLA allelic distribution in this population was in accordance with Hardy–Weinberg expectation (p > 0.05). A total of 173 HLA~A‐B~DRB1 haplotype with a frequency of >0.1% were presented and the three most common haplotype were HLA‐A*33:03~B*58:01~DRB1*03:01 (6.12%), HLA‐A*11:01~B*15:02~DRB1*12:02 (3.39%) and HLA‐A*11:01~B*15:02~DRB1*15:01 (3.22%). The phylogenetic tree and the principal component analysis suggested that Nanning Han population had a relative close genetic relationship with Chinese Zhuang population and a relative distant genetic relationship with Northern Han Chinese. The information will be useful for anthropological studies, for HLA matching in transplantation and disease association studies in the Chinese population. [ABSTRACT FROM AUTHOR]

We determined the high-resolution allele and haplotype frequencies at the human leucocyte antigen ( HLA)A, B and DRB1 loci in the Han population of Hubei province, the TB endemic area of Central China, with pulmonary tuberculosis ( PTB), and established the relationship between HLA-A, B and DRB1 alleles as well as haplotypes and susceptibility to multidrug-resistant and rifampicin-resistant tuberculosis ( MDR/ RR- TB). Blood samples were drawn from 174 patients with MDR/ RR- TB and 838 patients with drug-susceptible PTB in ethnic Han population from Hubei province (central China). Four-digit allele genotyping of HLA- A, B and DRB1 loci was performed using polymerase chain reaction with sequence-specific oligonucleotide probes (PCR- SSOP). The allele and haplotype frequencies of HLA-A, B and DRB1 were determined and compared between patients with MDR/ RR- TB and patients with drug-susceptible PTB. Statistical analysis of the generated data indicated no departure from expectation of Hardy-Weinberg equilibrium ( HWE) at all loci of the control group. Multivariate analysis identified allele DRB1*08:01 ( p < .0001; OR = 174.5, 95% CI 15.3-1987.2) as independent predictor of MDR/ RR- TB, except for old age ( p < .0001; OR = 10. 9, 95% CI 7.6-15.8), previous treatment history ( p < .0001; OR = 11.0, 95% CI 7.2-16.7) and poor compliance to treatment ( p < .0001; OR = 12.9, 95% CI 8.4-20.0). While in the subgroup of new TB cases, DRB1*08:01 ( p < .0001; OR = 80.3, 95% CI 7.0-917.1) and older age ( p < .0001; OR = 3.9, 95% CI 2.4-6.4) were independent susceptibility factors for primary MDR/ RR- TB. Our results suggest that a combination of clinical and host genetic information about tuberculosis patients may contribute to prediction and early detection of MDR/ RR- TB. [ABSTRACT FROM AUTHOR]

The major histocompatibility complex ( MHC) is located in chromosome 6p21 and contains crucial regulators of immune response, including human leucocyte antigen ( HLA) genes, alongside other genes with nonimmunological roles. More recently, a repertoire of noncoding RNA genes, including expressed pseudogenes, has also been identified. The MHC is the most gene dense and most polymorphic part of the human genome. The region exhibits haplotype-specific linkage disequilibrium patterns, contains the strongest cis- and trans- eQTLs/me QTLs in the genome and is known as a hot spot for disease associations. Another layer of complexity is provided to the region by the extreme structural variation and copy number variations. While the HLA-B gene has the highest number of alleles, the HLA- DR/ DQ subregion is structurally most variable and shows the highest number of disease associations. Reliance on a single reference sequence has complicated the design, execution and analysis of GWAS for the MHC region and not infrequently, the MHC region has even been excluded from the analysis of GWAS data. Here, we contrast features of the MHC region with the rest of the genome and highlight its complexities, including its functional polymorphisms beyond those determined by single nucleotide polymorphisms or single amino acid residues. One of the several issues with customary GWAS analysis is that it does not address this additional layer of polymorphisms unique to the MHC region. We highlight alternative approaches that may assist with the analysis of GWAS data from the MHC region and unravel associations with all functional polymorphisms beyond single SNPs. We suggest that despite already showing the highest number of disease associations, the true extent of the involvement of the MHC region in disease genetics may not have been uncovered. [ABSTRACT FROM AUTHOR]

Turner syndrome ( TS) is one of the most common sexual chromosome abnormalities and is clearly associated with an increased risk of autoimmune diseases, particularly thyroid disease and coeliac disease ( CD). Single-nucleotide polymorphism analyses have been shown to provide correlative evidence that specific genes are associated with autoimmune disease. Our aim was to study the functional polymorphic variants of PTPN22 and ZFAT in relation to thyroid disease and those of MYO9B in relation to CD. A cross-sectional comparative analysis was performed on Mexican mestizo patients with TS and age-matched healthy females. Our data showed that PTPN22 C1858T (considered a risk variant) is not associated with TS (X2 = 3.50, p = .61, and OR = 0.33 [95% CI = 0.10-1.10]). Also, ZFAT was not associated with TS (X2 = 1.2, p = .28, and OR = 1.22 [95% CI = 0.84-1.79]). However, for the first time, rs2305767 MYO9B was revealed to have a strong association with TS (X2 = 58.6, p = .0001, and OR = 10.44 [95% C = 5.51-19.80]), supporting a high level of predisposition to CD among TS patients. This report addresses additional data regarding the polymorphic variants associated with autoimmune disease, one of the most common complications in TS. [ABSTRACT FROM AUTHOR]

Although the TIM gene family plays important roles in immune responses, little is known about TIM regulation in the development of systemic lupus erythematosus ( SLE). This study aimed to investigate the association of two TIM-4 single nucleotide polymorphisms ( SNPs) rs6874202 (−1419G>A) and rs62382402 (−1609G>A) with SLE susceptibility in a Chinese Han population. The results showed no significant differences between patients with SLE and control group for rs6874202 and rs62382402 ( p = .72, .53 respectively). However, the anti-ds DNA levels in serum from SLE patients with GG genotype of TIM-4 gene at -1419 site were significantly higher than those with GA and AA genotype ( p = .0335), and C3 levels of SLE patients with GG and GA genotype were much lower than those with AA genotypes ( p = .0187). Moreover, the apoptotic cell levels of SLE patients with AA and GG genotypes were significantly higher than those with GA genotypes in patients with SLE ( p = .0393). In addition, the C3 concentration of SLE patients with the GG genotype of TIM-4 gene at -1609 site was found to be significantly higher than those with the GA genotype ( p = .0129). The results imply that GG genotype of the TIM-4 gene at -1419 site might be associated with the disease activity of SLE. [ABSTRACT FROM AUTHOR]