Institution: University of Cape Town

Project Affiliation: Establishment of an H3Africa Biorepository at Clinical Laboratory Services

Abstract

Background: Inborn errors of immunity (IEIs) or primary immunodeficiency diseases, are disorders caused by genetic defects affecting immune function. The prevalence of IEI both globally, and in South Africa, is still poorly understood for several reasons including underdiagnosis, under-reporting, and lack of awareness among physicians. Currently, the South African Primary Immunodeficiency Registry (SAPIDR), has approximately 396 participants registered. Although IEI are considered rare, systematic reviews of IEI registries suggested that certain IEI may be present in as many as 1:5000 to 1:1000 live births. Antibody deficiencies are considered the commonest of the IEI. South Africa also has a high prevalence of Human Immunodeficiency Virus (HIV) infection and even in infants who are exposed but uninfected, immunity may be compromised. In South Africa there are about 3.8 million people living with HIV (PLWH). With these stats it is logical to assume that there are several PLWH that also have IEI. In PLWH, other causes of immunodeficiency are typically not considered and the prevalence of coexistent IEI in PLWH is unknown. It is likely, however, that in these individuals, the immunodeficiency will be synergistic resulting in poorer outcomes.
Aims and Objectives: The aim is to look at the prevalence of IEI in people living with HIV. To achieve the aim using appropriate tools, mutations in genes associated with IEI will be identified from Whole genome sequencing (WGS) data from PLWH.
Methods: WGS data of PLWH will be selected from the H3A data Archive following an application to the Data and biospecimen access committee. Alignment and variant calling will be performed using Burrows-Wheeler Aligner (BWA) software. Annotation and variant prioritization will be performed using an appropriate tool in consultation with bioinformatics expert. By focusing on genes associated with inborn errors of immunity, gene defects causing specific IEI will be identified. Participants with the gene defects will be diagnosed with IEI of immunity depending on the inheritance patterns. The initial project will consider only genes associated with non-adult and adult onset of humoral IEIs. Following identification, permission will be sought to retrieve relevant clinical data. Biostatistician will be consulted to assist with analysis.

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