Approach to primary immunodeficiency

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 gamma 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.