Abstract
Tumor necrosis factor receptor-1–associated periodic syndrome (TRAPS) is the most common autosomal dominant autoinflammatory disorder and is caused by mutations in the TNFRSF1A gene encoding the 55-kDa receptor for tumor necrosis factor (TNF)-α. TRAPS is characterized by recurrent attacks of fever, typically lasting from 1 to 3 weeks. In addition to fever, common clinical features include periorbital edema, a migratory erythematous plaque simulating erysipela with underlying myalgia, and arthralgia or arthritis. Serosal membrane inflammation is also a common feature, usually in the form of polyserositis. To date, at least 40 different TNFRSF1A mutations have been identified, but few patients with symptoms highly suggestive of TRAPS with no mutations in the TNFRSF1A gene have recently been described, thus suggesting that not all mutations are yet known or that alternative mechanisms might be involved in the pathogenesis of the disease. We report on three such patients here.
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References
McDermott MF, Aksentijevich I, Galon J et al (1999) Germline mutations in the extracellular domains of the 55 kDa TNF receptor, TNFR1, define a family of dominantly inherited autoinflammatory syndromes. Cell 97:133–144
Dodé C, André M, Bienvenu T, Hausfater P, Pêcheux C, Bienvenu J et al (2002) French Heraditary Recurrent Inflammatory Disorder Study Group. The enlarging clinical, genetic, and population spectrum of tumor necrosis factor receptor-associated periodic syndrome. Arthritis Rheum 46:2181–2188
Aganna E, Hammond L, Hawkins PN et al (2003) Heterogeneity among patients with tumor necrosis factor receptor-associated periodic syndrome phenotypes. Arthritis Rheum 48:2632–2644
Touitou I, Lesage S, McDermott M, Cuisset L, Hoffman H, Dode C et al (2004) Infevers: an evolving mutation database for auto-inflammatory syndromes. Human Mutat 24:194–198
Hehlgans T, Pfeffer K (2005) The intriguing biology of the tumour necrosis factor/tumour necrosis factor receptor superfamily: players, rules and the games. Immunology 115:1–20
Banner DW, D’Arcy A, Janes W, Gentz R, Schoenfeld HJ, Broger C et al (1993) Crystal structure of the soluble human 55 kd TNF receptor-human TNF beta complex: implications for TNF receptor activation. Cell 73:431–445
Chan FK, Chun HJ, Zheng L, Siegel RM, Bui KL, Lenardo MJ (2000) A domain in TNF receptors that mediates ligand-independent receptor assembly and signaling. Science 288:2351–2354
Aksentijevich I, Galon J, Soares M, Mansfield E, Hull K, Oh HH et al (2001) The tumor-necrosis-factor receptor-associated periodic syndrome: new mutations in TNFRSF1A, ancestral origins, genotype-phenotype studies, and evidence for further genetic heterogeneity of periodic fevers. Am J Hum Genet 69:301–314
Lobito AA, Kimberley FC, Muppidi JR, Komarow H, Jackson AJ, Hull KM et al (2006) Abnormal disulfide-linked oligomerization results in ER retention and altered signaling by TNFR1 mutants in TNFR1-associated periodic fever syndrome (TRAPS). Blood 108:1320–1327
Nedjai B, Hitman GA, Yousaf N, Chernajovsky Y, Stjernberg-Salmela S, Pettersson T et al (2008) Abnormal tumor necrosis factor receptor I cell surface expression and NF-kappaB activation in tumor necrosis factor receptor-associated periodic syndrome. Arthritis Rheum 58:273–283
D’Osualdo A, Ferlito F, Prigione I, Obici L, Meini A, Zulian F et al (2006) Neutrophils from patients with TNFRSF1A mutations display resistance to tumor necrosis factor-induced apoptosis: pathogenetic and clinical implications. Arthritis Rheum 54:998–1008
Nedjai B, Hitman GA, Quillinan N, Coughlan RJ, Church L, McDermott MF et al (2009) Proinflammatory action of the antiinflammatory drug infliximab in tumor necrosis factor receptor-associated periodic syndrome. Arthritis Rheum 60:619–625
Dodé C, Papo T, Fieschi C, Pêcheux C, Dion E, Picard F et al (2000) A novel missense mutation (C30S) in the gene encoding tumor necrosis factor receptor 1 linked to autosomal-dominant recurrent fever with localized myositis in a French family. Arthritis Rheum 43:1535–1542
Hajeer AH, Hutchinson IV (2000) TNF-alpha gene polymorphism: clinical and biological implications. Microsc Res Tech 50:216–228
Drewe E, Powell RJ (2002) Novel treatments for tumor necrosis factor receptor-associated periodic syndrome (TRAPS): case history of experience with infliximab and sirolimus post etanercept. Clin Exp Rheum 4:71
Jacobelli S, André M, Alexandra JF, Dodé C, Papo T (2007) Failure of anti-TNF therapy in TNF receptor 1-associated periodic syndrome (TRAPS). Rheumatology (Oxford) 46:1211–1212
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L. Cantarini and O. M. Lucherini contributed equally.
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Cantarini, L., Lucherini, O.M., Cimaz, R. et al. Typical and severe tumor necrosis factor receptor–associated periodic syndrome in the absence of mutations in the TNFRSF1A gene: a case series. Rheumatol Int 32, 4015–4018 (2012). https://doi.org/10.1007/s00296-010-1512-4
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DOI: https://doi.org/10.1007/s00296-010-1512-4