Primary immunodeficiency diseases are inherited defects of the innate or adaptive arms of the immune system that lead to an increase in the incidence, frequency, or severity of
infections and/or immune dysregulation. There may be defects in the adaptive arm of the immune system, including combined immunodeficiencies and
antibody deficiency syndromes, or abnormalities in innate immunity, such as defects of phagocytes, the
complement pathway, or
toll-like receptor mediated signaling. Recurrent sinopulmonary
infections with encapsulated bacteria such as Haemophilus influenzae type B or Streptococcus pneumoniae may be characteristic of an
antibody deficiency syndrome. Frequent viral, fungal, or protozoal
infections may suggest T lymphocyte impairment. Multiple Staphylococcus skin
infections and
fungal infections may imply neutrophil dysfunction or the
Hyper-IgE syndrome, and recurrent Neisseria
infection is a characteristic manifestation of late
complement component (C5-9, or the
membrane attack complex) defects. Recurrent viral or pyogenic
bacterial infections, often without the presence of a significant inflammatory response, suggest a defect in
toll-like receptor signaling. Mycobacterial
infections are characteristic of defects in the
interleukin (
IL) 12/
interferon γ pathway. Screening of newborns for T-cell
lymphopenia by using polymerase chain reaction to amplify
T-cell receptor excision circles, which are formed when a T cell rearranges the variable region of its receptor, serves as a surrogate for newly synthesized naive T cells. Because of very low numbers of
T-cell receptor excision circles,
severe combined immunodeficiency, 22q11.2 syndrome, and other causes of T-cell
lymphopenia have been identified in newborns.