[1] To be considered a primary immunodeficiency (PID), the immune deficiency must be inborn, not caused by secondary factors such as other disease, drug treatment, or environmental exposure to toxins.
Most primary immunodeficiencies are genetic disorders; the majority are diagnosed in children under the age of one, although milder forms may not be recognized until adulthood.
Research is currently evaluating the use of stem cell transplants (HSCT) and experimental gene therapies as avenues for treatment in limited subsets of PIDs.
Particular organ problems (e.g. diseases involving the skin, heart, facial development and skeletal system) may be present in certain conditions.
Others predispose to autoimmune disease, where the immune system attacks the body's own tissues, or tumours (sometimes specific forms of cancer, such as lymphoma).
The International Union of Immunological Societies recognizes nine classes of primary immunodeficiencies, totaling over 120 conditions.
Although there is a therapeutic option, gene therapy which has been in a trial for few immune deficiencies affecting the hematopoietic system.
However, it is rarely used because of a risk of developing post-treatment T-cell leukemia as a result of interfering tumor-suppressor genes[14] and because of ethical issues.
This figure does not take into account people with mild immune system defects who have not received a formal diagnosis.
[16] Milder forms of primary immunodeficiency, such as selective immunoglobulin A deficiency, are fairly common, with random groups of people (such as otherwise healthy blood donors) having a rate of 1:600.
[17] Virus-specific T-lymphocytes (VST) therapy is used for patients who have received hematopoietic stem cell transplantation that has proven to be unsuccessful.
These new methods have reduced culture time to 10–12 days by using specific cytokines from adult donors or virus-naive cord blood.
This treatment is far quicker and with a substantially higher success rate than the 3–6 months it takes to carry out HSCT on a patient diagnosed with a primary immunodeficiency.
[21] Discovery of novel genetic causes of innate immunodeficiencies accelerated greatly in the 2010s due to high-throughput DNA sequencing technologies.