Dataset Information

Human Leukocyte Antigen Diversity: A Southern African Perspective.

ABSTRACT: Despite the increasingly well-documented evidence of high genetic, ethnic, and linguistic diversity amongst African populations, there is limited data on human leukocyte antigen (HLA) diversity in these populations. HLA is part of the host defense mechanism mediated through antigen presentation to effector cells of the immune system. With the high disease burden in southern Africa, HLA diversity data is increasingly important in the design of population-specific vaccines and the improvement of transplantation therapeutic interventions. This review highlights the paucity of HLA diversity data amongst southern African populations and defines a need for information of this kind. This information will support disease association studies, provide guidance in vaccine design, and improve transplantation outcomes.

SUBMITTER: Tshabalala M

PROVIDER: S-EPMC4549606 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Human Leukocyte Antigen Diversity: A Southern African Perspective.

Tshabalala Mqondisi M Mellet Juanita J Pepper Michael S MS

Journal of immunology research 20150812

Despite the increasingly well-documented evidence of high genetic, ethnic, and linguistic diversity amongst African populations, there is limited data on human leukocyte antigen (HLA) diversity in these populations. HLA is part of the host defense mechanism mediated through antigen presentation to effector cells of the immune system. With the high disease burden in southern Africa, HLA diversity data is increasingly important in the design of population-specific vaccines and the improvement of t ...[more]

PMID: 26347896

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Project description:Backround: Leprosy is very prevalent in many populations around the world, which is well known that both alleles for human leukocyte antigen (HLA) as well as single nucleotide polymorphisms (SNPs) in the HLA region are common in leprosy patients. Previous studies have identified leprosy-associated susceptibility genes that explain only part of disease risk and heritability. In view of the complicated characteristics of the major histocompatibility complex (MHC) region, this study aimed to explore the development and variation of HLA in leprosy and its possible mechanism. Methods: Previous genome-wide association data were extracted from Han and minority populations in southern China for HLA fine-mapping studies. Insertion and deletion (INDEL), SNP, and copy number variation (CNV) imputation were determined by using the Thousand People Database (1KGP Phase 3 Dataset) as a reference panel. The HAN-MHC database was used to input the HLA classical alleles and amino acids in the MHC region, and further step-regression analysis was performed to analyze independent variation signals associated with leprosy. Results: The most significant locus rs75324027 (the same locus as rs602875 in the HLA-DR region) [p = 7.49E-09, OR= 0.62, 95%,CI: 0.52-0.73] in the intergene region between HLA-DQA1 and HLA-DRB1 was related with leprosy in M-S(Han leprosy patients in south China)disease. In M-SM (Leprosy patients of ethnic minorities in south China)disease, one of the most significant loci of the HLA-DQB1 gene was 6-32626438-A-T (p = 4.49E-08, OR = 0.36, 95%,CI: 0.25-0.52). Therefore, rs75324027 is a locus in M-S disease, and 6-32626438-a-T may be a new locus in M-SM disease. The interaction between 6 and 32626438-A-T and RS75324027 was analyzed, and A significant interaction relationship was found. In the optimal model, the accuracy of prediction was 0.5974, cross-validation Consistency:10, p = 0.0107. Conclusion: In conclusion, this study is the first to assess the association between HLA and leprosy susceptibility in Han and other minority populations in southern China using the Thousand Population database and the Han MHC database. In addition, our analysis validated the previously reported locus rs602875 in the HLA-DR region and for the first time identified an unreported independent locus in leprosy among ethnic minorities in southern China.

Project description:Recent studies have suggested that plasma-derived proteins may be potential biomarkers relevant for graft-versus-host disease and/or non-relapse mortality occurring after allogeneic blood or marrow transplantation. However, none of these putative biomarkers have been assessed in patients treated either with human leukocyte antigen-haploidentical blood or marrow transplantation or with post-transplantation cyclophosphamide, which has been repeatedly associated with low rates of severe acute graft-versus-host disease, chronic graft-versus-host disease, and non-relapse mortality. We explored whether seven of these plasma-derived proteins, as measured by enzyme-linked immunosorbent assays, were predictive of clinical outcomes in post-transplantation cyclophosphamide-treated patients using plasma samples collected at serial predetermined timepoints from patients treated on prospective clinical studies of human leukocyte antigen-haploidentical (n=58; clinicaltrials.gov Identifier: 00796562) or human leukocyte antigen-matched-related or -unrelated (n=100; clinicaltrials.gov Identifiers: 00134017 and 00809276) T-cell-replete bone marrow transplantation. Day 30 levels of interleukin-2 receptor ?, tumor necrosis factor receptor 1, serum STimulation-2 (IL1RL1 gene product), and regenerating islet-derived 3-? all had high areas under the curve of 0.74-0.97 for predicting non-relapse mortality occurrence by 3 months post-transplant in both the human leukocyte antigen-matched and human leukocyte antigen-haploidentical cohorts. In both cohorts, all four of these proteins were also predictive of subsequent non-relapse mortality occurring by 6, 9, or 12 months post-transplant and were significantly associated with non-relapse mortality in univariable analyses. Furthermore, day 30 elevations of interleukin-2 receptor ? were associated with grade II-IV and III-IV acute graft-versus-host disease occurring after day 30 in both cohorts. These data confirm that plasma-derived proteins previously assessed in other transplantation platforms appear to retain prognostic and predictive utility in patients treated with post-transplantation cyclophosphamide.

Dataset Information

Human Leukocyte Antigen Diversity: A Southern African Perspective.

Publications

Human Leukocyte Antigen Diversity: A Southern African Perspective.

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