PID

Phenocopies associated with somatic mutations.

• ALPS-SFAS defect: somatic mutations in TNFRSF6 gene. Double-negative T cells increased splenomegaly, lymphadenopathy, autoimmune cytopenias. Apoptosis defect
• RAS-associated autoimmune leukoproliferative disease (RALD): Somatic mutation in KRAS (GOF). Double-negative T cells normal. Splenomegaly, lymphadenopathy, autoimmune cytopenias, granulocytosis, monocytosis/ALPS-like.
• RAS-associated autoimmune leukoproliferative disease (RALD): Somatic mutation in NRAS (GOF). Double-negative T cells increased, lymphocytosis, splenomegaly, lymphadenopathy, autoantibodies/ALPS-like.
• Cryopyrinopathy (similar to Muckle-Wells/CINCA/NOMID): Somatic mutation in NLRP3 gene. urticarial exanthema, arthropathy, neurological abnormalities.
• Hypereosinophilia syndrome as distinct from myeloid neoplasms with eosinophilia.

Phenocopies associated with autoantibodies

• CMC: autoantibodies against IL-17 and/or IL-22

Immunodeficiency with susceptibility to mycobacteria in adulthood

• Autoantibodies to IFN-γ. Decrease in naive T cells. Mycobacterial, fungal, salmonella, VZV infections. MSMD or CID.
• Recurrent skin and visceral infections: autoantibodies against IL-6, secondary STAT3 deficiency.
• Pulmonary alveolar proteinosis: autoantibodies against GM-CSF. CSF2RA deficiency: pulmonary alveolar proteinosis, cryptococcal meningitis, disseminated nocardiosis.
• Acquired angioedema: autoantibodies to C1 INH; C1 esterase inhibitor deficiency.
• Atypical HUS: autoantibodies to H. Spontaneous activation of the alternative pathway.
• Good syndrome (agammaglobulinemia with thymoma): Autoantibodies against various cytokines. CD8 elevated, no B cells: Invasive bacterial, viral or opportunistic infections, autoimmunity, PRCA, lichen planus, cytopenia, colitis, chronic diarrhea.