Human Leukocyte Antigen Diversity: A Southern African Perspective

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 defensemechanism 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.The Medical Research Council of South Africa in terms of MRC’s Flagships Awards Project SAMRCRFA-UFSP-01-2013/STEM CELLS, the Institute for Cellular and Molecular Medicine of the University of Pretoria, and the National Research Foundation of South Africa.http://www.hindawi.com/journals/jiram2016Immunolog

A COVID-19 vaccine : big strides come with big challenges

As of 8 January 2021, there were 86,749,940 confirmed coronavirus disease 2019 (COVID19) cases and 1,890,342 COVID-19-related deaths worldwide, as reported by the World Health Organization (WHO). In order to address the COVID-19 pandemic by limiting transmission, an intense global effort is underway to develop a vaccine against SARS-CoV-2. The development of a safe and effective vaccine usually requires several years of pre-clinical and clinical stages of evaluation and requires strict regulatory approvals before it can be manufactured in bulk and distributed. Since the global impact of COVID-19 is unprecedented in the modern era, the development and testing of a new vaccine are being expedited. Given the high-level of attrition during vaccine development, simultaneous testing of multiple candidates increases the probability of finding one that is effective. Over 200 vaccines are currently in development, with over 60 candidate vaccines being tested in clinical trials. These make use of various platforms and are at different stages of development. This review discusses the different phases of vaccine development and the various platforms in use for candidate COVID-19 vaccines, including their progress to date. The potential challenges once a vaccine becomes available are also addressed.The South African Medical Research Council and the University of Pretoria.http://www.mdpi.com/journal/vaccinespm2022Immunolog

Constituting a public umbilical cord blood bank in South Africa

No abstract availableThe South African Medical Research Council of in terms of the MRC’s Flagships Awards Project SAMRC-RFA-UFSP-01-2013/STEM CELLS, the Institute for Cellular and Molecular Medicine of the University of Pretoria, and the National Research Foundation of South Africa.http://www.nature.com/bmt2015-09-30hb201

Consequences of HIV infection in the bone marrow niche

Dysregulation of the bone marrow niche resulting from the direct and indirect effects of HIV infection contributes to haematological abnormalities observed in HIV patients. The bone marrow niche is a complex, multicellular environment which functions primarily in the maintenance of haematopoietic stem/ progenitor cells (HSPCs). These adult stem cells are responsible for replacing blood and immune cells over the course of a lifetime. Cells of the bone marrow niche support HSPCs and help to orchestrate the quiescence, self-renewal and differentiation of HSPCs through chemical and molecular signals and cell-cell interactions. This narrative review discusses the HIV-associated dysregulation of the bone marrow niche, as well as the susceptibility of HSPCs to infection by HIV.The NRF-DAAD program, the University of Pretoria, the National Research Foundation, the Bill and Melinda Gates Foundation and the South African Medical Research Council.http://www.frontiersin.org/Immunologyam2024ImmunologySDG-03:Good heatlh and well-bein

Perspectives on establishing a public cord blood inventory in South Africa

The South African population is highly diverse, both ethnically and genetically. This diversity is particularly true for the African ancestry and various mixed ancestry population groups. These groups are under-represented in national and international bone marrow and peripheral blood donor registries, making it challenging to identify HLA-matched and mismatched unrelated donors when patients from these groups require allogeneic hematopoietic stem and progenitor cell transplantation. In most high-income countries, banked cord blood (CB) units provide an attractive source of hematopoietic progenitor cells for genetically diverse populations. SA does not have a public CB inventory, leaving many patients without access to this important treatment modality. Haploidentical transplantation provides an alternative. In recent years, the use of post-transplant cyclophosphamide has significantly reduced the incidence of graft-versus-host disease after haploidentical transplantation and has improved transplantation outcomes. However, it is difficult to identify suitable haploidentical donors in SA because of family disruption and a high prevalence of HIV. Here the authors provide a brief historical overview of the ethnic and genetic diversity of the country and region. The authors provide a southern African perspective on HLA diversity, consider the allogeneic hematopoietic stem and progenitor cell transplantation landscape and explore the need to establish a public CB bank (CBB) in SA. The health policy and regulatory frameworks that will impact on a CBB in the country SA are also explored. Finally, the authors discuss several matters we believe require attention when considering the establishment of a sustainable public CBB in the South African context.The South African Medical Research Council (Extramural Unit, Stem Cell Research and Therapy) and the University of Pretoria (Institute for Cellular and Molecular Medicine).http://www.isct-cytotherapy.orghttps://www.journals.elsevier.com/cytotherapyhj2022Immunolog

Consequences of HIV infection in the bone marrow niche

Dysregulation of the bone marrow niche resulting from the direct and indirect effects of HIV infection contributes to haematological abnormalities observed in HIV patients. The bone marrow niche is a complex, multicellular environment which functions primarily in the maintenance of haematopoietic stem/progenitor cells (HSPCs). These adult stem cells are responsible for replacing blood and immune cells over the course of a lifetime. Cells of the bone marrow niche support HSPCs and help to orchestrate the quiescence, self-renewal and differentiation of HSPCs through chemical and molecular signals and cell-cell interactions. This narrative review discusses the HIV-associated dysregulation of the bone marrow niche, as well as the susceptibility of HSPCs to infection by HIV

Open access and its potential impact on public health – a South African perspective

Traditionally, access to research information has been restricted through journal subscriptions. This means that research entities and individuals who were unable to afford subscription costs did not have access to journal articles. There has however been a progressive shift toward electronic access to journal publications and subsequently growth in the number of journals available globally. In the context of electronic journals, both open access and restricted access options exist. While the latter option is comparable to traditional, subscription-based paper journals, open access journal publications follow an “open science” publishing model allowing scholarly communications and outputs to be publicly available online at no cost to the reader. However, for readers to enjoy open access, publication costs are shifted elsewhere, typically onto academic institutions and authors. SARS-CoV-2, and the resulting COVID-19 pandemic have highlighted the benefits of open science through accelerated research and unprecedented levels of collaboration and data sharing. South Africa is one of the leading open access countries on the African continent. This paper focuses on open access in the South African higher education research context with an emphasis on our Institution and our own experiences. It also addresses the financial implications of open access and provides possible solutions for reducing the cost of publication for researchers and their institutions. Privacy in open access and the role of the Protection of Personal Information Act (POPIA) in medical research and secondary use of data in South Africa will also be discussed.The South African Medical Research Council Extramural Unit for Stem Cell Research and Therapy and the University of Pretoria through the Institute for Cellular and Molecular Medicine and the Bill and Melinda Gates Foundation.https://www.frontiersin.org/journals/research-metrics-and-analyticshj2022Immunolog

Human leukocyte antigen (HLA) diversity and clinical applications in South Africa

The major histocompatibility complex, known as the human leukocyte antigen (HLA) complex in humans, forms an integral component of adaptive T cell immunity by presenting self and non-self peptides to the T cell receptor, thereby allowing clonal expansion of responding peptide-specific CD4+ and CD8+ T cells. HLA likewise forms an integral part of the innate immune response through the binding of killercell immunoglobulin-like receptor (KIR) molecules, which regulate the response of natural killer (NK) cells. The HLA complex is found on the short arm of chromosome 6 and is the most polymorphic region in the human genome. Africans are genetically more diverse than other populations; however, information on HLA diversity among southern Africans, including South African populations, is limited. Paucity of African HLA data limits our understanding of disease associations, the ability to identify donor-recipient matches for transplantation and the development of disease-specific vaccines. This review discusses the importance of HLA in the clinical setting in South Africans and highlights how tools such as HLA imputation might augment standard HLA typing methods to increase our understanding of HLA diversity in our populations, which will better inform disease association studies, donor recruitment strategies into bone marrow registries and our understanding of human genetic diversity in South Africa.http://www.samj.org.zapm2020Immunolog

The NESHIE and CP Genetics Resource (NCGR): A database of genes and variants reported in neonatal encephalopathy with suspected hypoxic ischemic encephalopathy (NESHIE) and consequential cerebral palsy (CP)

DATA AVAILABILTY : All data generated or analysed during this study are included in this published article, supplementary information files, and the NCGR database repository. Access to the NCGR database is available at http://ncgr.bi.up.ac.za/. Additional data will be made available on request.SUPPLEMENTARY DATA : SUPPLEMENTARY FIG. 1. User input for a complex query generated using NCGR's filter functionality to prioritise genes likely to predispose individuals to NESHIE. Abbreviations: CP: cerebral palsy; NESHIE: neonatal encephalopathy with suspected hypoxic ischemic encephalopathy; HPO: human phenotype ontology; NCGR: NESHIE and CP genetics resource.SUPPLEMENTARY FIG. 2. Protein-protein interaction network constructed using genes that were prioritised based on evidence of potential involvement in a genetic predisposition to neonatal encephalopathy with suspected hypoxic ischaemic encephalopathy (NESHIE). Protein products of the input set of genes are represented by blue nodes. Additional direct and secondary interactors of the input set are represented in grey.SUPPLEMENTARY DATA A. Methods used to perform gene ontology enrichment and protein-protein interaction network analyses.SUPPLEMENTARY DATA B. Gene Ontology enrichment resultsSUPPLEMENTARY TABLE 1. Variant Details table data.SUPPLEMENTARY TABLE 2. Ensembl Variant Effect Prediction table data.SUPPLEMENTARY TABLE 3. Gene Details table data.SUPPLEMENTARY TABLE 4. Gene Human Phenotype Ontology table data.SUPPLEMENTARY TABLE 5. MutationTaster Variant Effect Prediction table data.SUPPLEMENTARY TABLE 6. Study Details table data.SUPPLEMENTARY TABLE 7. Study Findings table data.Neonatal encephalopathy (NE) with suspected hypoxic ischaemic encephalopathy (HIE) (NESHIE) is a complex syndrome occurring in newborns, characterised by altered neurological function. It has been suggested that genetic variants may influence NESHIE susceptibility and outcomes. Unlike NESHIE, for which a limited number of genetic studies have been performed, many studies have identified genetic variants associated with cerebral palsy (CP), which can develop from severe NESHIE. Identifying variants in patients with CP, as a consequence of NESHIE, may provide a starting point for the identification of genetic variants associated with NESHIE outcomes. We have constructed NCGR (NESHIE and CP Genetics Resource), a database of genes and variants reported in patients with NESHIE and CP (where relevant to NESHIE), for the purpose of collating and comparing genetic findings between the two conditions. In this paper we describe the construction and functionality of NCGR. Furthermore, we demonstrate how NCGR can be used to prioritise genes and variants of potential clinical relevance that may underlie a genetic predisposition to NESHIE and contribute to an understanding of its pathogenesis.The Bill & Melinda Gates Foundation, Seattle, USA; the South African Medical Research Council, Cape Town, South Africa; and the University of Pretoria through the Institute for Cellular and Molecular Medicine.https://www.elsevier.com/locate/ygenohj2023BiochemistryGeneticsImmunologyMicrobiology and Plant Patholog