Around one in 500 people are born with what is called a primary immunodeficiency – an immune system deficiency which does not have an underlying cause such as infection, drug treatment, or environmental exposure to a toxic substance.
Most primary immunodeficiencies are caused by genetic disorders, and are the result of the body’s inability to manufacture a specific protein which plays a role in one or more arms of the immune response.
There are eight classes of primary immunodeficiencies, and around 120 specific conditions.
- T and B Cells: These disorders involve a deficiency in either T cells, B cells, or both – there may be reduced numbers of cells, or none at all. Individuals with so-called Severe Combined Immuno-Deficiency diseases are extremely vulnerable to infection, as they lack any kind of adaptive immune response (also meaning they can not develop any kind of immunological memory).
- Antibody: One or more types of antibody is produced in reduced amounts, or is non-functional. Effects vary depending on the type of antibody involved – generally, an individual is more susceptible to bacterial or opportunistic infections.
- Phagocytes: Disorders which affect these cells generally result in reduced cell numbers, or cells which cannot function normally. People with these disorders tend to suffer recurrent infections of specific types, depending on which cell types are deficient.
- Complement: A deficiency in the complement cascade can predispose an individual to bacterial infections or autoimmune disorders. However, the complement system has many redundancies, and in some cases a genetic defect in this system may have no effect at all.
- Innate Immune Deficiencies: The innate immune system is a much more basic line of immunological defense than the adaptive system, and individuals with innate disorders tend to be less severely affected. Innate immune disorders tend to lead to recurrent viral infections, particularly human papilloma virus. In some cases, however, the adaptive immune system is also deficient, leading to more severe symptoms.
- Autoinflammatory Disorders: These diseases do not predispose to particular types of infection – instead they result in excessive inflammatory responses, potentially leading to long-term damage in organs and tissues.
- Immune Dysregulation Disorders: The immune system’s ability to regulate itself is compromised. Depending on the nature of the genetic defect, the results may include increased or decreased numbers of immune cells, enlarged organs, or defective immune cells. Some disorders can also cause autoimmunity.
- Well-defined Syndromes: These are disorders which do not fit in other categories, but which have well-defined symptoms and clinical features. One such disorder is Hyper-IgE Syndrome, characterized by over-production of IgE, recurrent and severe infections, and skin rashes.