HLA System Research Articles

Nomenclature for factors of the HLA system, update October, November and December 2022.

Nomenclature for factors of the HLA system, update October, November and December 2022.

Nomenclature for factors of the HLA system, update October, November and December 2022

Nomenclature for factors of the HLA system, update October, November and December 2022

Nomenclature for factors of the HLA system, update October, November and December 2022.

Nomenclature for factors of the HLA system, update October, November and December 2022.

The role of the HLA allelic repertoire on the clinical severity of COVID-19 in Canadians, living in the Saskatchewan province

AimsThe HLA system has been implicated as an underlying determinant for modulating the immune response to SARS-CoV-2. In this study, we aimed to determine the association of patients’ HLA genetic profiles with the disease severity of COVID-19 infection. MethodsProspective study was conducted on COVID-19 patients (n = 40) admitted to hospitals in Saskatoon, Canada, between March and December 2020. Next-generation sequencing was performed on the patient samples to obtain high-resolution HLA typing profiles. The statistical association between HLA allelic frequency and disease severity was examined. The disease severity was categorized based on the length of hospital stay and intensive care needs or demise during the hospital stay. ResultsHLA allelic frequencies of the high and low-severity cohorts were normalized against corresponding background allelic frequencies. In the high-severity cohort, A*02:06 (11.8-fold), B*51:01 (2.4-fold), B*15:01(3.1-fold), C*01:02 (3.3-fold), DRB1*08:02 (31.2-fold), DQ*06:09 (11-fold), and DPB1*04:02(4-fold) were significantly overrepresented (p < 0.05) making these deleterious alleles. In the low-severity cohort, A*24:02 (2.8-fold), B*35:01 (2.8-fold), DRB1*04:07 (5.3-fold), and DRB1*08:11 (22-fold) were found to be significantly overrepresented (p < 0.05) making these protective alleles. These above alleles interact with NK cell antiviral activity via the killer immunoglobulin-like receptors (KIR). The high-severity cohort had a higher predilection for HLA alleles associated with KIR subgroups; Bw4-80I (1.1-fold), and C1 (1.6-fold) which promotes NK cell inhibition, while the low-severity cohort had a higher predilection for Bw4-80T (1.6-fold), and C2 (1.6-fold) which promote NK cell activation. ConclusionIn this study, the HLA allelic repository with the distribution of deleterious and protective alleles was found to correlate with the severity of the clinical course in COVID-19. Moreover, the interaction of specific HLA alleles with the KIR-associated subfamily modulates the NK cell-mediated surveillance of SARS-CoV-2. Both deleterious HLA alleles and inhibitory KIR appear prominently in the severe COVID-19 group focusing on the importance of NK cells in the convalescence of COVID-19.

West Nile virus-associated HLA-DRB1 alleles in the Greek population: A structural perspective.

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

Nomenclature for factors of the HLA system, update April, May and June 2022

Nomenclature for factors of the HLA system, update April, May and June 2022

LncRNA HCG11 suppresses cell proliferation in hormone receptor-positive breast cancer via SRSF1/β-catenin.

Hormone receptor positive (HR-positive) breast cancer (BC) is the most common subtype of breast cancer. Despite adjuvant endocrine therapy and chemotherapy-based treatment, the therapeutic response is often not satisfactory in HR-positive BC patients. Therefore, elucidating the mechanisms that regulate the progression of HR-positive BC is urgently required to identify new therapeutic targets. Previously, HLA Complex Group 11 (HCG11), located on the major histocompatibility complex (MHC) region, was found to be abnormally expressed in a variety of tumor cells. However, the role of HCG11 in HR-positive BC cells has not been explored to date. In the current study, we found that HCG11 is downregulated in HR-positive BC tissues and cell lines. Both in vitro and in vivo, HCG11 acts as a tumor suppressor in HR-positive BC cells. Furthermore, the mechanistic details unraveled that HCG11 recruits Serine/arginine-rich splicing factor 1 (SRSF1) to target β-catenin mRNA for promoting the translation of β-catenin. Our study emphasizes the potential of HCG11 as a novel intervention target for HR-positive BC treatment.

A historical perspective on HLA.

The discovery of the history of the HLA system is reviewed from the earliest attempts at cancer transfers between mice, through the discovery of the mouse H-2 system on mouse red blood cells, the discovery of HLA class II and II antigens by use of sera from multiparous women, to the resolution of the HLA and H-2 functions explained by the attachment of intra cellular peptides to the HLA antigen grooves on the cell surface. The study of the associations between HLA types and diseases forms the basis for the subsequent extensive study of the genetics of human complex disease and phenotypes by GWAS (Genome Wide Association Studies).

LncRNA HLA Complex Group 11 Knockdown Alleviates Cisplatin Resistance in Gastric Cancer by Targeting the miR-144-3p/UBE2D1 Axis [Retraction

[This retracts the article DOI: 10.2147/CMAR.S329846.].

Retracted: Long Noncoding RNA HLA Complex Group 18 Improves the Cell Proliferation of Myocardial Fibroblasts by Regulating the Hsa-microRNA-133a/Epidermal Growth Factor Receptor Axis.

[This retracts the article DOI: 10.1155/2022/2668239.].

Olfatory HLA-associated mechanism of formation of married couples in the development of congenital heart diseases in children

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

The HLA profile and genetic affinities of three primitive Tamil-speaking endogamous groups: Kallars of Thanjavur, Piramalai Kallar and Vanniyar

BackgroundThe present study was aimed to study the frequencies of HLA-DRB1/-DQB1 alleles and haplotypes of three endogamous groups of Tamil Nadu state, South India. PCR-SSP typing of HLA-DRB1 and -DQB1 alleles were performed on 111 Kallars of Thanjavur, 80 Piramalai Kallar of Madurai and 119 Vanniyar. Genetic distances, neighbor-joining phylogenetic dendrograms and correspondence analysis have been performed.ResultsThe HLA class II alleles, DRB1*07 (25.2%), DRB1*15 (15.7%), DRB1*14 (11.7%) and DRB1*12 (9.90%) among Kallars of Thanjavur; DRB1*15 (28.7%), DRB1*04 (15.6%), DRB1*10 (14.3%), DRB1*13 (11.2%) and DRB1*03 (9.37%) among Piamalai Kallar and DRB1*15 (24.7%), DRB1*04 (15.9%), DRB1*07 (11.7%), DRB1*12 (11.3%) and DRB1*10 (10.0%) among Vanniyar were more frequent. Similarly, alleles DQB1*06 (31.0%), DQB1*02 (26.5%) and DQB1*05 (24.7%) among Kallars of Thanjavur; DQB1*05 (32.5%), DQB1*06 (31.8%), DQB1*02 (16.2%) and DQB1*03:02 (12.5%) among Piramalai Kallar and DQB1*05 (52.9%), DQB1*06 (22.6%) and DQB1*02 (11.3%) among Vanniyar were more frequent. We genotyped the two most frequent two-locus haplotypes, such as DRB1*15-DQB1*06 and DRB1*07-DQB1*02 for HLA-A/-B/–C alleles to identify the 5-locus extended haplotypes to extrapolate global affinities. We identified a number of five locus extended haplotypes among south Indian population with stronger global affinities. Further, we identified the presence of a highly unique extended haplotypes such as A*11-B*35-C*12-DRB1*07-DQB1*02 (HF:0.1458) in Kallars of Thanjavur, A*03-B*35-C*04-DRB1*15-DQB1*06 (HF:0.1833) in Piramalai Kallar and A*03-B*07-C*07-DRB1*15-DQB1*06 (HF: 0.1800) in Kallars of Thanjavur and (HF: 0.1081) in Vanniyar population.ConclusionsAllele distribution and haplotype analysis have demonstrated that the Kallars of Thanjavur, Piramalai Kallar and Vanniyar populations shared HLA alleles with other ethnic and other Indian populations, while showing population specific haplotypes. Analysis of population-specific distribution of HLA alleles is proved to be important in finding out the relatedness of the ethnic groups across continents. The extensive polymorphism of the HLA system also has useful application in the study of the origin, evolution and migration patterns of human populations.

LncRNA HCG18 Promotes Osteosarcoma Cells Proliferation, Migration, and Invasion in by Regulating miR-34a/RUNX2 Pathway.

Osteosarcoma (OS) is a type of tumor with high malignant behaviors. Increasing investigates have confirmed that long non-coding RNA HLA complex group 18 (lncRNA HCG18) acted as a tumor-promoting factor in multiple tumors. Nevertheless, the underlying mechanism of HCG18 on OS remains largely unclear. HCG18, miR-34a, and runt-related transcription factor 2 (RUNX2) expressions were detected by quantitative real-time PCR (RT-qPCR) or western blotting assays, respectively. The underlying tumorigenic phenotypes were detected by MTT, wound healing, transwell invasion, western blotting assays. Molecular interactions were verified by dual-luciferase report assay. HCG18 and RUNX2 were notably enhanced, whereas miR-34a was decreased in OS tumor tissues and cell lines. Functional experiments uncovered that HCG18 silencing significantly inhibited the capabilities of proliferation, migration, and invasion, while overexpression of HCG18 play the opposite roles. Furthermore, HCG18 directly bound to miR-34a, and miR-34a was confirm to be a negative regulator of RUNX2. Interestingly, the anti-tumor effects of HCG18 silencing were attenuated by miR-34a inhibitor and RUNX2 overexpression. Taken together, the present study suggested that HCG18 promoted the malignant biological behaviors of OS through regulating the miR-34a/RUNX2 pathway, implying HCG18 might serve as a new target for OS treatment.

Human leukocyte antigen system associations in Malassezia-related skin diseases.

The human leukocyte antigen system (HLA) is divided into two classes involved in antigen presentation: class I presenting intracellular antigens and class II presenting extracellular antigens. While susceptibility to infections is correlated with the HLA system, data on associations between HLA genotypes and Malassezia-related skin diseases (MRSD) are lacking. Thus, the objective of this study was to investigate associations between HLA alleles and MRSD. Participants in The Danish Blood Donor Study (2010-2018) provided questionnaire data on life style, anthropometric measures, and registry data on filled prescriptions. Genotyping was done using Illumina Infinium Global Screening Array, and HLA alleles were imputed using the HIBAG algorithm. Cases and controls were defined using filled prescriptions on topical ketoconazole 2% as a proxy of MRSD. Logistic regressions assessed associations between HLA alleles and MRSD adjusted for confounders and Bonferroni corrected for multiple tests. A total of 9455 participants were considered MRSD cases and 24,144 participants as controls. We identified four risk alleles B*57:01, OR 1.19 (95% CI: 1.09-1.31), C*01:02, OR 1.19 (95% CI: 1.08-1.32), C*06:02, OR 1.14 (95% CI: 1.08-1.22), and DRB1*01:01, OR 1.10 (95% CI: 1.04-1.17), and two protective alleles, DQB1*02:01, OR 0.89 (95% CI: 0.85-0.94), and DRB1*03:01, OR 0.89 (95% CI: 0.85-0.94). Five novel associations between HLA alleles and MRSD were identified in our cohort, and one previous association was confirmed. Future studies should assess the correlation between Malassezia antigens and antigen-binding properties of the associated HLA alleles.

The IPD-IMGT/HLA Database.

It is 24 years since the IPD-IMGT/HLA Database, http://www.ebi.ac.uk/ipd/imgt/hla/, was first released, providing the HLA community with a searchable repository of highly curated HLA sequences. The database now contains over 35 000 alleles of the human Major Histocompatibility Complex (MHC) named by the WHO Nomenclature Committee for Factors of the HLA System. This complex contains the most polymorphic genes in the human genome and is now considered hyperpolymorphic. The IPD-IMGT/HLA Database provides a stable and user-friendly repository for this information. Uptake of Next Generation Sequencing technology in recent years has driven an increase in the number of alleles and the length of sequences submitted. As the size of the database has grown the traditional methods of accessing and presenting this data have been challenged, in response, we have developed a suite of tools providing an enhanced user experience to our traditional web-based users while creating new programmatic access for our bioinformatics user base. This suite of tools is powered by the IPD-API, an Application Programming Interface (API), providing scalable and flexible access to the database. The IPD-API provides a stable platform for our future development allowing us to meet the future challenges of the HLA field and needs of the community.

Nomenclature for factors of the HLA system, update July, August and September 2022.

International Journal of ImmunogeneticsEarly View NOMENCLATURE Nomenclature for factors of the HLA system, update July, August and September 2022 Steven G. E. Marsh, Corresponding Author Steven G. E. Marsh steven.marsh@ucl.ac.uk Anthony Nolan Research Institute, Royal Free Hospital, London, UK Correspondence Professor Steven GE Marsh, Anthony Nolan Research Institute, Royal Free Hospital, Pond Street, London NW3 2QG, UK. Email: steven.marsh@ucl.ac.ukSearch for more papers by this author Steven G. E. Marsh, Corresponding Author Steven G. E. Marsh steven.marsh@ucl.ac.uk Anthony Nolan Research Institute, Royal Free Hospital, London, UK Correspondence Professor Steven GE Marsh, Anthony Nolan Research Institute, Royal Free Hospital, Pond Street, London NW3 2QG, UK. Email: steven.marsh@ucl.ac.ukSearch for more papers by this author First published: 02 November 2022 https://doi.org/10.1111/iji.12603Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Early ViewOnline Version of Record before inclusion in an issue RelatedInformation

Nomenclature for factors of the HLA system, update July, August and September 2022: Compiled by Steven G.E. Marsh for the WHO Nomenclature Committee for Factors of the HLA System

Nomenclature for factors of the HLA system, update July, August and September 2022: Compiled by Steven G.E. Marsh for the WHO Nomenclature Committee for Factors of the HLA System

A simple approach for detecting HLA-A*02 alleles in archival formalin-fixed paraffin-embedded tissue samples and an application example for studying cancer immunoediting.

The HLA system represents a central component of the antigen presentation machinery. As every patient possesses a defined set of HLA molecules, only certain antigens can be presented on the cell surface. Thus, studying HLA type-dependent antigen presentation can improve the understanding of variation in susceptibility to various diseases, including infectious diseases and cancer. In archival formalin-fixed paraffin-embedded (FFPE) tissue, the HLA type is difficult to analyze because of fragmentation of DNA, hindering the application of commonly used assays that rely on long DNA stretches. Addressing these difficulties, we present a refined approach for characterizing presence or absence of HLA-A*02, the most common HLA-A allele in the Caucasian population, in archival samples. We validated our genotyping strategy in a cohort of 90 samples with HLA status obtained by an NGS-based method. 90% (n=81) of the samples could be analyzed with the approach. For all of them, the presence or absence of HLA-A*02 alleles was correctly determined with the method, demonstrating 100% sensitivity and specificity (95% CI: 91.40%-100% and 91.19%-100%). Furthermore, we provide an example of application in an independent cohort of 73 FFPE microsatellite-unstable (MSI) colorectal cancer samples. As MSI cancer cells encompass a high number of mutations in coding microsatellites, leading to the generation of highly immunogenic frameshift peptide antigens, they are ideally suited for studying relations between the mutational landscape of tumor cells and interindividual differences in the immune system, including the HLA genotype. Overall, our method can help to promote studying HLA type-dependency during the pathogenesis of a wide range of diseases, making archival and historic tissue samples accessible for identifying HLA-A*02 alleles.

Target induction of heme oxygenase-1 attenuates anti-HLA I antibody induced transplant vasculopathy in an allogeneic aortic transplantation model in mice

Abstract Introduction After solid organ transplantation every second patient develops transplant vasculopathy (TV), which still remains the major obstacle for long-term graft survival. The main risk factor for developing TV are de novo synthesized donor-specific antibodies binding molecules of the MHC complex (HLA complex in humans, respectively) on the surface of endothelial cells (EC). EC become activated, vascular smooth muscle cells proliferate, and monocytes are recruited, contributing the development of the neointima a hallmark of TV. We have demonstrated that the anti-HLA I antibody (w6/32) significantly increases transmigration of monocytes across an endothelial monolayer in vitro. These interactions were dependent on modulating the anti-inflammatory enzyme heme oxygenase (HO)-1. Purpose The aim of the project is to investigate which adhesion molecule might mediate the antibody-induced transmigration of monocytes sensitive to HO-1 modulation and whether this modulation has beneficial effects in an allogenic aortic transplantation model in mice. Methods Before w6/32 stimulation, HO-1 was modulated by pretreating Human Coronary Artery Endothelial Cells (HCAEC) either with CoPPIX as a HO-1 activator or with statins to test for a therapeutic approach. Expression of a variety of established adhesion receptors in HCAEC was screened after HO-1 modulation and w6/32 stimulation. Antibody-induced transmigration and adhesion of THP-1 were quantified in the presence of CD62E-blocking antibodies. Thoracic aorta was transplanted into the abdominal aorta between fully MHC mismatched mice and applying the corresponding anti-MHC I antibody (SF1-1.1) induced TV. Mice were treated with CoPPIX, statins or CORM to evaluate the effects of HO-1 modulation or its metabolite CO on TV development. Statistical evaluation was performed with t-test or ANOVA. Results HO-1 modulation in HCAEC diminished w6/32-induced THP-1 transmigration. CD62E-expression in HCAECs was enhanced after w6/32 stimulation on mRNA and protein level, but preincubation with CoPPIX or statins reduced these effects. Incubation of HCAEC with a CD62E-blocking antibody after w6/32 stimulation significantly diminished the rate of transmigration normalized to isotype-stimulated HCAEC (isotype 100%, w6/32 + IgG 226% vs. w6/32 + CD62E-block 138%, p&amp;lt;0.05.). Treatment of mice with CoPPIX resulted in a significant reduction of the SF1-1.1-induced number of transmigrated monocytes (SF1-1.1: 10 vs. CoPPIX: 5.4; p&amp;lt;0.05). Application of statins (SF1-1.1: 10 vs. statin 6.6; p&amp;lt;0.05) or CORM (CORM: 6.1 vs. iCORM: 11.3, p&amp;lt;0.05) significantly reduces monocyte number as well. In all treatment groups, the SF1-1.1-induced neointima formation was ameliorated. Conclusion w6/32-induced monocyte transmigration is CD62E-dependent. SF1-1.1-induced monocytic infiltrate and intimal hyperplasia in a murine aortic transplantation model is also CD62E dependent and amenable to HO-1 modulation. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This sudy was funded by the German Research Foundation to Jan Larmann

Nomenclature for factors of the HLA system, update April, May and June 2022

Nomenclature for factors of the HLA system, update April, May and June 2022