Table 9.

Phenocopies of PID

Disease	Genetic defect/presumed pathogenesis	Circulating T cells	Circulating B cells	Serum Ig	Associated features/similar PID
Associated with somatic mutations
Autoimmune lymphoproliferative syndrome (ALPS–SFAS)	Somatic mutation in TNFRSF6	Increased CD4−CD8−double negative (DN) T alpha/beta cells	Normal, but increased number of CD5+ B cells	Normal or increased	Splenomegaly, lymphadenopathy, autoimmune cytopenias Defective lymphocyte apoptosis/ALPS–FAS (=ALPS type Im)
RAS-associated autoimmune leukoproliferative disease (RALD)	Somatic mutation in KRAS (gain-of-function)	Normal	B cell lymphocytosis	Normal or increased	Splenomegaly, lymphadenopathy, autoimmune cytopenias, granulocytosis, monocytosis/ALPS-like
RAS-associated autoimmune leukoproliferative disease (RALD)	Somatic mutation in NRAS (gain-of-function)	Increased CD4−CD8−double negative (DN) T alpha/beta cells	Lymphocytosis		Splenomegaly, lymphadenopathy, autoantibodies/ALPS-like
Cryopyrinopathy, (Muckle-Wells /CINCA/NOMID-like syndrome)	Somatic mutation in NLRP3	Normal	Normal	Normal	Urticaria-like rash, arthropathy, neurological symptoms
Associated with autoantibodies
Chronic mucocutaneous candidiasis (isolated or with APECED syndrome)	Germline mutation in AIRE AutoAb to IL-17 and/or IL-22	Normal	Normal	Normal	Endocrinopathy, chronic mucocutaneous candidiasis/CMC
Adult-onset immunodeficiency	AutoAb to IFN gamma	Decreased naive T cells	Normal	Normal	Mycobacterial, fungal, Salmonella VZV infections/MSMD, or CID
Recurrent skin infection	AutoAb to IL-6	Normal	Normal	Normal	Staphylococcal infections/STAT3 deficiency
Pulmonary alveolar proteinosis	AutoAb to GM-CSF	Normal	Normal	Normal	Pulmonary alveolar proteinosis, cryptococcal meningitis/CSF2RA deficiency
Acquired angioedema	AutoAb to CI inhibitor	Normal	Normal	Normal	Angioedema/C1 INH deficiency (hereditary angioedema)
Atypical Hemolytic Uremic Syndrome	AutoAb to Complement Factor H	Normal	Normal	Normal	aHUS Spontaneous activation of the alternative complement pathway