Primary immunodeficiencies (also known as PIDs) are rare, affecting only 1 in 20,000 – 50,000 individuals. PIDs are usually inherited conditions with genetic mutations passed down by one or both parents, but they are always caused by errors in single genes.
To date, researchers have found mutations in around 300 genes that cause distinct primary immunodeficiencies, including B cell (antibody) deficiencies, T cell deficiencies, and combinations of these.
- Diagnosis & Treatment
Some forms of PID are so mild they may go unnoticed for years while other types are so severe they’re discovered almost as soon as an affected baby is born. Without effective intervention, many result in irreversible complications and death before the end of the first year of life.
Secondary Immunodeficiency Disease refers to immunodeficiencies that are acquired. Anything that weakens your immune system can lead to a secondary immunodeficiency disorder, including treatments to suppress the immune system as in organ transplants, certain cancers, underlying diseases such as HIV infection, or poor nutrition in at-risk populations. Secondary immunodeficiency diseases lead to an increased incidence of infection, malignancy or autoimmune disease.
For that small group born with a Primary Immunodeficiency (PID), their immune system does not function normally, leaving them open to infections. These may be more frequent, more severe, longer lasting or harder to treat than for someone with a normal immune system, but they may also get infections that a person with a healthy immune system is unlikely to get.
Babies and children with severe PID suffer from recurrent viral, bacterial, fungal or parasitic infections, as well as an inability to respond to some vaccinations. This makes them vulnerable to many childhood infections we are usually protected against.
Depending on the type of PID, signs and symptoms can include frequent and recurrent:
- Pneumonia, bronchitis or sinus
- Ear or skin infections
- Meningitis inflammation and infection of internal organs
- Blood disorders
- Digestive problems, such as cramping, loss of appetite, nausea and diarrhoea.
PID can also lead to:
- delayed growth and development
- autoimmune disorders such as lupus, rheumatoid arthritis, inflammatory bowel disease or type 1 diabetes.
Children with PID can also be more likely to develop cancer due to a breakdown in the ability of the immune system to recognise and respond to malignant cells.
PID will usually be diagnosed in childhood, but some people might only be diagnosed as adults despite having been unwell from an early age.
Diagnosing immunodeficiency can be a lengthy process requiring a range of tests and examinations in order to understand if recurrent infections may be due to primary immunodeficiency. A medical history, including a review of any possible inherited family immune system disorders, may also require a variety of additional testing:
- Blood tests to measure levels of blood cells, immune system cells and infection-fighting proteins or immunoglobulin.
- Prenatal testing. Parents who’ve had a child with a primary immunodeficiency disorder may want to be tested for certain immunodeficiency disorders during future pregnancies.
- DNA testing for a specific genetic defect or whole-genome sequencing to discover the full array of possible genetic variations.
As individuals usually present with an infection, the first line of treatment is often an antimicrobial – antibiotics, anti-viral, antifungal – along with monthly antibody replacement therapy. Antibody therapy is lifelong and these patients will remain vulnerable to infection, but if the patient has severe PID they may need a bone marrow transplant from a healthy donor.
Some of these diseases are known as ‘severe combined immune deficiency’ or ‘combined immune deficiency’ where affected Individuals are susceptible to many different types of microbes. These conditions are often fatal unless treated by a compatible stem cell transplant.
Even where the spectrum of infections is much narrower and many infections can be treated with antibiotics, these PIDs can also be life-shortening, if not fatal.