Table 1.

Immunodeficiencies affecting cellular and humoral immunity

SCID/CID spectrum: Infants with SCID who have maternal T cell engraftment may have T cells in normal numbers that do not function normally; these cells may cause autoimmune cytopenias or graft versus host disease. Hypomorphic mutations in several of the genes that cause SCID may result in Omenn syndrome (OS), or “leaky” SCID, or still less profound combined immunodeficiency (CID) phenotypes. Both OS and leaky SCID can be associated with >300 autologous T cells/uL of peripheral blood and reduced, rather than absent, proliferative responses when compared with typical SCID caused by null mutations. A spectrum of clinical findings including typical SCID, OS, leaky SCID, CID, granulomas with T lymphopenia, autoimmunity and CD4 T lymphopenia can be found in an allelic series of RAG1/2 and other SCID-associated genes. There can be clinical overlap between some genes listed here and those listed in Table 7

Total number of mutant genes: 66. New inborn errors of immunity: 8 (SLP76 [12], PAX1 [13, 14], ITPKB [15]; SASH3 [16, 17], MAN2B2 [18], COPG1 [19], IKZF2 [20–23], CHUK [24])

SCID severe combined immunodeficiency, CID combined immunodeficiency, EBV Epstein-Barr virus, MHC major histocompatibility complex, HPV human papillomavirus, Treg T regulatory cell, XL X-linked inheritance, AR autosomal recessive inheritance, AD autosomal dominant inheritance, LOF loss-of-function, GOF gain-of-function, FTT failure to thrive