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Division of Molecular Biology and Human Genetics

Primary Immunodeficiency Disease and Tuberculosis Susceptibility,
Genetic Research Group

​A Primary Immunodeficiency Disease (PID) is an inherited defect in the immune system that leads to a predisposition to infections and or manifestations of autoimuunity. More than 230 PIDs have been characterised to date, with several new disorders being added every year .

In our environment, PIDs are frequently underdiagnosed or easily missed because:

  • Infectious diseases are common in South Africa
  • Awareness of PIDs is lacking - they are still regarded as rare diseases, and hence the recognition of features suggesting a possible PID (see Box1), is limited
  • Although clinical algorithms and basic laboratory tests can lead to a probable diagnosis, the extended laboratory testing for PIDDs is complex and expensive, and transport of samples for immunological testing can be challenging.

To improve data collection and relevant information on PIDs in South Africa, a PID registry was established in 2008. This is curated by Dr Monika Esser, a Paediatric Rheumatologist in charge of the Clinical Immunology service at Tygerberg Hospital. Employed by the National Health Laboratory Service at Tygerberg Hospital, Dr Esser is the prinicpal investigator of the registry at Stellenbosch University. The South African PID registry, apart from having ethical permission at SU, also has PIs and ethical approval at the University of Cape Town and the University of the Witwatersrand. Currently the registry has information on about 300 PID patients, a small fraction of the expected number of PID cases in the population. In Africa more broadly, there are estimated to be 900 000 individuals with a PID, but only several thousand have been diagnosed and registered to date.  The SA registry diagnoses reflect a similar pattern of genetic disease to those of the European ESID registry with more than 50% related to antibody deficiencies. These conditions can be treated and major morbidity can be prevented by early

diagnosis.Improvements in the diagnosis of PIDs will result in earlier and appropriate treatment, in addition to the improved quality of life and survival of patients affected by these conditions. Defining genetic suceptibility to infections will also augment our understanding of the role of PIDs in the infections that are prevalent in developing country settings, such as Tuberculosis.

Tuberculosis is caused by an intracellular pathogen, Mycobacterium tuberculosis. Some PIDs are known to affect areas of the immune system that are crucial in the defence against Tuberculosis (TB) and other intracellular pathogens. Examples of such PIDs include Mendelian Susceptibility to Mycobacterial Diseases (MSMD) which are associated with infections of low- virulence Mycobacteria but also salmonellosis. Chronic Granulomatous Disease (CGD), and Severe Combined Immunodeficiency Disease (SCID) are further examples of PIDs which confer an increased risk of disease from TB. Investigation of patients with as yet unexplained recurrent Tuberculosis may yield further insights into both PIDs and the immunology of Tuberculosis.

Box 1: Signs that a patient might have a PID include:

  • Infections which are severe or difficult to treat, persistent or recurrent, or due to unusual organisms
  • Specifically recurrent pneumonia, ear infections, sinusitis, or chronic diarrhoea, structural damage eg bronchiectasis
  • Multiple courses of oral antibiotics or need for IV antibiotics to clear infections (then termed major infections)
  • Recurrent deep abscesses of organs eg liver or skin
  • Failure to thrive
  • Skin rashes, especially atypical eczema. Swollen lymph glands, enlarged spleen and or liver
  • Features of autoimmunity
  • A family history of PIDD