Can a genetic defect cause your immune system to malfunction?

Posted on 9 May 2018

In South Africa, when we think of lowered immunity, we are prone to think of common causes such as HIV/AIDS, malnutrition, stress, pregnancy or even common medical treatments that lower immunity. However, if someone is particularly prone to infections that simply don’t clear up, another cause may be to blame. Primary immunodeficiency diseases (PID) are a group of chronic disorders in which part of the body’s immune system isn’t functioning correctly.

‘Primary Immunodeficiencies are more common than once appreciated,’ says Prof Monika Esser, Specialist Rheumatologist at the University of Stellenbosch. They range from minor immunodeficiencies such as IgA deficiencies, seen in about one in every 400 people, to severe combined immunodeficiencies. Also known as SCID or Bubble Boy disease, these are fortunately far more rare at about 1 reported case per 50 000 newborn screenings.’

A genetic disease

Newborn screening is not routinely performed in South Africa, therefore our figures are derived from countries in the US where screening for SCID is almost uniformly practised at birth now.

Boys normally have one Y chromosome and one X chromosome, while girls have two X chromosomes. If defective genes are passed down from a mother to her son, the absence of a second X chromosome may mean that the genetic defect is expressed in the son, while it was dormant in his mother or sister who then remains carriers of the gene.

Primary Immunodeficiencies are commonly X-linked and passed down from parents or grandparents, however, they may also arise as spontaneous mutations or changes in the genes, according to Prof Esser.

‘About 300 such immune defects are now recognised with 10000 expected to be identified in future with rapid advances in genetic diagnostics,’ she says.

‘In South Africa, 350 patients have been reported to the National Registry since 2008, however, this is the tip of the iceberg. We estimate the true number to be around 6000 (for a population of close to 60 million) people,’ says Prof Esser.

As the diseases have a genetic basis, they are not passed on from person to person like viruses or bacterial infections. Instead, they lower the sufferer’s particular defence against infectious diseases such as colds and flu or manifest commonly with infections of the upper and lower respiratory systems or other organs. They may also paradoxically manifest with autoimmune diseases.

Treatment progresses in leaps and bounds

‘Since the first description of the diagnosis and treatment of a boy who was unable to produce the antibody immunity to fight bacterial infections, there have been rapid advances in genetics to define these “experiments of nature” in the immune system. Genetics helps to make an accurate diagnosis and to be able to counsel for risk of a recurrent gene in a family. It also allows for researchers to compare patients with a similar genetic defect who may present with many different clinical signs,’ explains Dr Esser.

‘For at least 50% percent of patients, the deficiency can be treated with antibody replacement therapy (IVIG- intravenous immunoglobulin replacement or SCIg – subcutaneous immunoglobulin replacement which can be administered to the patient). Both therapies are readily available in South Africa (the only African country with its own production plant for this product derived from local blood donations). Milder immune deficits may improve as children grow up and their immune system matures and compensates for the condition. Other effective methods include regular vaccinations and judiciously supervised prophylactic antibiotics where absolutely necessary.

‘Serious immune deficit patients may need stem cell transplantation even if diagnosed early especially if there is a family history of the disease.

‘Earliest diagnosis and treatment prevents damage to organs and regular supervised treatment should enable many patients to lead normal productive lives,’ explains Prof Esser.

But diagnoses are often delayed, hence screening tests must be discussed with your doctor in the setting of SPUR infections (severe, persistent, unusual, recurrent). Baseline screening in HIV negative patients includes full blood count, immunoglobulins, testing for Tuberculosis and a sweat test for Cystic Fibrosis where indicated by the history.

‘If a patient has access to good nutrition, vaccinations are up to date, HIV testing is negative, and especially if they have a family history of immunodeficiency, one must ask the question: why is he or she getting SPUR infections? Good history taking for warning signs and basic laboratory tests can diagnose up to 50% of PID cases,’ explains Prof Esser.

In the future, with a confirmed genetic disorder, gene therapy may be able correct the defective genes which cause serious deficiencies. Fortunately, access to genetic testing is becoming increasingly affordable and available to confirm rarer, frequently missed diseases such as PID and thereby enable targeted treatment choices.

For those newly diagnosed with Primary Immunodeficiency, South Africa offers a support group in the form of PiNSA (Primary Immunodeficiency Network of South Africa link to:

Doctors can benefit by getting in touch with the Primary Immune Deficiency Diseases South Africa (PIDDSA) working group of the Allergy Society of South Africa for further up-to-date information.


Published in Magazine

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