OP0122 Tumour necrosis factor-receptor associated periodic syndrome in a finnish family

Abstract

Background TNF receptor-associated periodic syndrome (TRAPS) is a recently defined dominantly inherited autoinflammatory syndrome, which is caused by mutations in the extracellular domains of the 55 kDa TNF receptor, TNFRSF1A. TRAPS is characterised by periodic fevers, sterile peritonitis, pleurisy, arthritis, erysipeloid erythema of the skin, and conjunctivitis. Affected individuals have shown a shedding defect of TNFRSF1A upon stimulation and, consequently, low levels of soluble TNFRSF1A in serum. Objectives We studied a three-generation Finnish family, where recurrent attacks of fever and abdominal pain appeared to segregate as an autosomal dominant trait. Methods The TNFRSF1A gene was sequenced in both affected and unaffected family members. Flow cytometric analysis and ELISA analyses were used to assess membrane expression and serum levels of TNFRSF1A, respectively. Results A missense mutation of exon 4, resulting in an amino acid substitution (F112I) close to a conserved cysteine and disulphide bond, was detected in 4 affected family members and in one asymptomatic family member. Impaired shedding of TNFRSF1A after phorbol myristate acetate stimulation was detected in peripheral blood monocytes and granulocytes from affected individuals. The soluble TNFRSF1A levels of individuals carrying the mutation (n = 5) were about half of soluble TNFRSF1A levels of individuals not carrying the mutation (n = 4). Conclusion Dominantly inherited autoinflammatory syndrome should be suspected whenever a patient presents with a history of intermittent fevers accompanied by abdominal pain, arthritis or skin rashes, particularly in the presence of a positive family history. Among such patients, low serological levels of soluble TNFRSF1A give an indication of those individuals who are likely to have TRAPS. Reference McDermott MF, Aksentijevich I, Galon J, et al . Germline mutations in the extracellular domains of the 55 kDa TNF receptor, TNFR1, define a family of dominantly inherited autoinflammatory syndromes. Cell 1999;97:133–44