Examples of PID Syndromes with Associated Autoimmune Manifestations
| Associated Genetic Defect(s) | Syndrome(s) W/ Autoimmune Problems | Affected Immunity |
|---|---|---|
| AIRE | APECED | T cell subset development |
| FOXP3 | IPEX | and tolerance |
| RAG1, RAG2 | CVID, CID, SCID | |
| RAG1, RAG2, DCLRE1C | Omenn syndrome | |
| CTLA4, LRBA | CVID, CID, hCTLA4 | Lymphocyte signaling |
| PI3K | CVID, CID | pathway |
| PKC-δ | CVID, CID, ALPS, SLE | |
| DOCK8 | DOCK8 syndrome | |
| LAT | CID, SCID | |
| JAK and STAT family | CMC and hyper IgE syndrome | |
| CD40L | Hyper-IgM | |
| Complement protein genes | SLE | Complement pathway |
| CASP10, CASP8, FAS, FASL, | ALPS | Abnormal resolution of |
| TNFSF6, TNFRSF6 | inflammation | |
| ACP5 | SPENCD | Interferon signaling |
| TMEM173 | SAVI | pathway |
AIRE = autoimmune regulator; APECED = autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy; FOXP3 = forkhead box P3; IPEX = immunodysregulation polyendocrinopathy enteropathy X-linked; RAG1, RAG2 = recombination activating gene 1, (and 2); DCLRE1C = Cross-Link Repair 1C, gene encoding “Artemis” protein; CVID = common variable immunodeficiency; (S)CID = (Severe) Combined Immunodeficiency; CTLA4 = cytotoxic T-lymphocyte associated protein 4 (also called CD152 or cluster of differentiation 152); LRBA = lipopolysaccharide-responsive and beige-like anchor protein; PI3K = phosphoinositide 3-kinase; PKC-d = protein kinase C delta; DOCK 8 = dedicator of cytokinesis 8; LAT = linker for activation of T cells; JAK STAT = Janus kinase, signal transducer and activator of transcription protein; CD40L = cluster of differentiation 40 ligand (also called CD154); ALPS = autoimmune lymphoproliferative syndrome; SLE = systemic lupus erythematosus; CMC = chronic mucocutaneous candidiasis; CASP8 and 10 = caspase 8, 10; FAS(L) = FS=7 associated surface antigen (ligand), also called CD95 or apoptosis antigen 1 or APO-1; TNFSF6 – tumor necrosis factor superfamily member 6; TNFRSF6 – tumor necrosis factor superfamily receptor member 6; ACP5 = acid phosphatase 5 (encodes tartrate resistant acid phosphatase (TRAP) protein; TMEM173 = transmembrane protein 173; SPENCD = spondyloenchondrodysplasia with immune dysregulation; SAVI = STING (stimulator of interferon genes) – associated vasculopathy
