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Human Genetic Disease associations TNF2 (G-308A) promotor polymorphism associated with increased susceptibility to septic shock. Asthma and RA severity Associated with SLE in GWAS X-linked hyper-IGM syndrome associated with CD40L loss of function mutations Autoimmune lymphoproliferative syndrome (ALPS) type Ib

Phenotype associated With Deficiency Absence of LN and PP, defective GC formation Defective GC formation, resistance to endotoxic shock and experimental arthritis Th2 deficiency, blockade improves EAE Immunodeficiency due to defective Ig class switching and germinal center formation Lymphadenopathy and systemic autoimmunity

Phenotype associated With Over Expression Wasting syndrome, arthritis Ectopic lymphoid organ formation Increased Th2 responses Constitutive expression in B cells or keratinocytes leads to SLE-like syndrome T-cell hyperactivation eventually leading to immunodeficiency (HIV-like)

Key Functions Lymphoid organ formation Inflammation Lymphoid organ formation CD4 T-cell expansion, survival, and Th2 development Costimulation and differentiation of B cells and APC Mediator of CD4(+) T-cell apoptosis as a result of restimulation and apoptosis in other cell types T-cell costimulation

OMIM ID 153440 TNFR2 (1B), TNFR1 (1A), HVEM (14) 191160 TNFR2 (1B), TNFR1 600978 heterotrimer with LTα binds to LTβ 603594 300386 134638 Fas (6), DcR3 (6B) 602840 603875

TNF Superfamily Cytokines Binds to receptor(s) aliases LT, TNFB, TNFSF1 TNFα, TNFSF2, (1A) CACHECTIN As a β 2 α 1 p33, TNFC, TNFSF3 receptor (3) OX40 (4) GP34, OX4OL, TXGP1, CD134L, OX-40 L CD40 (5) IGM, IMD3, TRAP, gp39, CD154, CD40L, HIGM1, T-BAM, FASL, CD178, CD95L, APT1LG1 CD27 (7) CD70, CD27L, CD27LG CD30 (8) CD153, CD30L, CD30LG

TABLE 9.2 Common Name Symbol Lymphotoxin TNFSF1 alpha (Ltα) Tumor necrosis TNFSF2 factor (TNF) Lymphotoxin TNFSF3 beta (LTβ) OX40 Ligand TNFSF4 CD40 Ligand TNFSF5 Fas Ligand TNFSF6 CD27 Ligand TNFSF7 CD30 Ligand TNFSF8