TNFRSF1A mutations and autoinflammatory syndromes

Citation
J. Galon et al., TNFRSF1A mutations and autoinflammatory syndromes, CURR OP IM, 12(4), 2000, pp. 479-486
Citations number
44
Language
INGLESE
art.tipo
Review
Categorie Soggetti
Immunology
Journal title
CURRENT OPINION IN IMMUNOLOGY
ISSN journal
0952-7915 → ACNP
Volume
12
Issue
4
Year of publication
2000
Pages
479 - 486
Database
ISI
SICI code
0952-7915(200008)12:4<479:TMAAS>2.0.ZU;2-6
Abstract
The autoinflammatory syndromes are systemic disorders characterized by appa rently unprovoked inflammation in the absence of high-titer autoantibodies or antigen-specific T lymphocytes. One such illness, TN F-receptor-associat ed periodic syndrome (TRAPS), presents with prolonged attacks of fever and severe localized inflammation. TRAPS is caused by dominantly inherited muta tions in TNFRSF1A (formerly termed TNFR1), the gene encoding the 55 kDa TNF receptor. All known mutations affect the first two cysteine-rich extracell ular subdomains of the receptor, and several mutations are substitutions di rectly disrupting conserved disulfide bonds. One likely mechanism of inflam mation in TRAPS is the impaired cleavage of TN FRSF1A ectodomain upon cellu lar activation, with diminished shedding of the potentially antagonistic so luble receptor. Preliminary experience with recombinant p75 TNFR-Fc fusion protein in the treatment of TRAPS has been favorable.