Primary immunodeficiency disorder, PID, refers to a large group of hundreds of conditions,
each caused by a defect in the immune system. Because the immune system protects the body
against infections, people with PID are more vulnerable to infectious diseases.
Most commonly, PID results from a mutation inherited from one or both parents.
It must be differentiated from secondary immunodeficiency caused by pathogens,
such as HIV, malnutrition, metabolic diseases, or use of immunosuppressive medications.
The major players of the immune system are the white blood cells. They derive from hematopoietic
stem cells in the bone marrow. Each cell has specific roles in the immune response.
The immune system consists of 2 branches: the innate response including phagocytes and
complement proteins; and the adaptive response involving T-cells and B-cells. T-cells are
primarily responsible for cellular immunity, and B-cells for antibody-mediated immunity,
but there are overlaps in their functions. PID can be classified based on the immune
component that is affected. Innate disorders include phagocyte and complement deficiencies.
Adaptive disorders include T-cell deficiencies, B-cell deficiencies, and combined T and B-cell
deficiencies, which are often severe. Because antibody production by B-cells requires T-cell
functions, T-cell deficiencies often lead to combined immunodeficiency disorders.
Severe forms of PID can be apparent soon after birth or during the first year of life,
while milder forms may go unnoticed until late childhood or even adulthood. Symptoms
vary greatly among different types, but the most telltale sign is having frequent, recurrent,
or particularly difficult to treat infections. Most common are respiratory, sinus, ear, and
skin infections. Infants often fail to grow. Blood disorders or autoimmune diseases may also occur.
Timely diagnosis, especially for severe forms, is essential to survival. Patients
of any age with repeated or unusual infections must be checked for PID.
Assessment usually starts with a complete blood count and blood smear to evaluate
the levels of lymphocytes. A low lymphocyte count may be indicative of T-cell deficiency.
Flow cytometry can be used to quantify specific cell types. Lymphocyte proliferation assays
are used to evaluate T-cell functions. Serum immunoglobulin levels are measured
when B-cell deficiency is suspected. Patients may be tested for their response to certain vaccine
antigens, such as tetanus toxoid. Failure to produce adequate amounts of antibody against the
antigen indicates antibody-deficiency disorder. Neutrophil function assays, cytokine stimulation
assays, and complement studies are helpful for diagnosis of innate disorders.
Disorders caused by known mutations can be confirmed with DNA testing.
Treatment consists of 2 major parts: treating, preventing infections; and
boosting the immune system, or possibly fixing it. Bacterial infections are managed with aggressive
antibiotic treatments. Preventive measures involve prophylactic antibiotics and vaccinations,
but live-attenuated vaccines must be avoided as they may cause severe diseases. Patients with
severe combined immunodeficiency should be protected from exposure to pathogens.
B-cell disorders are treated with intravenous or subcutaneous immunoglobulin replacement therapy.
Phagocyte disorders are managed with cytokine replacement therapy, such as interferon-gamma.
Bone marrow transplantation or hematopoietic stem cell transplantation may offer a permanent
cure if HLA-identical donors are available. Gene therapy, which introduces a normal copy
of the patient's mutated gene into relevant cells, has been successful for some disorders.