Table VII.

Autoinflammatory Disorders

Disease	Affected cells	Functional defects	Associated Features	Inheritance	Gene defects
Familial Mediterranean Fever	Mature granulocytes, cytokine-activated monocytes.	Decreased production of pyrin permits ASC-induced IL-1 processing and inflammation following subclinical serosal injury; macrophage apoptosis decreased.	Recurrent fever, serositis and inflammation responsive to colchicine. Predisoposes to vasculitis and inflammatory bowel disease.	AR	Mutations of MEFV
TNF receptor-associated periodic syndrome (TRAPS)	PMNs, monocytes	Mutations of 55-kD TNF receptor leading to intracellular receptor retention or diminished soluble cytokine receptor available to bind TNF	Recurrent fever, serositis, rash, and ocular or joint inflammation	AD	Mutations of TNFRSF1A
Hyper IgD syndrome		Mevalonate kinase deficiency affecting cholesterol synthesis; pathogenesis of disease unclear	Periodic fever and leukocytosis with high IgD levels	AR	Mutations of MVK
Muckle-Wells syndrome*	PMNs, monocytes	Defect in cryopyrin, involved in leukocyte apoptosis and NFkB signalling and IL-1 processing	Urticaria, SNHL, amyloidosis. Responsive to IL-1R/antagonist (Anakinra)	AD	Mutations of CIAS1 (also called PYPAF1 or NALP3)
Familial Cold autoinflammatory syndrome*	PMNs, chondrocytes	same as above	Non-pruritic urticaria, arthritis, chills, fever and leukocytosis after cold exposure. Responsive to IL-1R/antagonist (Anakinra)	AD	Mutations of CIAS1
Neonatal onset multisystem inflammatory disease (NOMID) or chronic infantile neurologic cutaneous and articular syndrome (CINCA)*	PMNs, chondrocytes	same as above	Neonatal onset rash, chronic meningitis, and arthropathy with fever and inflammation responsive to IL-1R antagonist (Anakinra)	AD	Mutations of CIAS1
Pyogenic sterile arthritis, pyoderma gangrenosum, acne (PAPA) syndrome	hematopoietic tissues, upregulated in activated T-cells	Disordered actin reorganization leading to compromised physiologic signaling during inflammatory response	Destructive arthritis, inflammatory skin rash, myositis	AD	Mutations of PSTPIP1 (also called C2BP1)
Blau syndrome	Monocytes	Mutations in nucleotide binding site of CARD15, possibly disrupting interactions with lipopolysaccharides and NF-κB signaling	Uveitis, granulomatous synovitis, camptodactyly, rash and cranial neuropathies, 30% develop Crohn's disease	AD	Mutations of NOD2 (also called CARD15)
Chronic recurrent multifocal osteomyelitis and congenital dyserythropoietic anemia (Majeed syndrome)	Neutrophils, bone marrow cells	Undefined	Chronic recurrent multifocal osteomyelitis, transfusion-dependent anemia, cutaneous inflammatory disorders	AR	Mutations of LPIN2

^*All three syndromes associated with similar CIAS1 mutations; disease phenotype in any individual appears to depend on modifying effects of other genes and environmental factors.

Abbreviations: As for Table 1; N, neutrophils; M, monocytes/macrophages; L, lymphocytes; NK, natural killer cells; AD, autosomal dominant inheritance. ASC, apoptosis-asocated speck-like protein with a caspase recruitment domain; CARD, caspase recruitment domain; CD2BP1, CD2 binding protein-1; PSTPIP1, Proline/serine/threonine phosphatase-interacting protein 1; SNHL - sensorineural hearing loss;CIAS1- cold-induced autoinflammatory syndrome 1