An autoinflammatory disease with deficiency of the interleukin-1-receptor antagonist.
Обработка статьи · этапы, ошибки и управление
Ошибки и ограничения
История · было → стало
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Aksentijevich Ivona, Masters Seth L, Ferguson Polly J, Dancey Paul, Frenkel Joost, van Royen-Kerkhoff Annet, Laxer Ron, Tedgård Ulf, Cowen Edward W, Pham Tuyet-Hang, Booty Matthew, Estes Jacob D, Sandler Netanya G, Plass Nicole, Stone Deborah L, Turner Maria L, Hill Suvimol, Butman John A, Schneider Rayfel, Babyn Paul, El-Shanti Hatem I, Pope Elena, Barron Karyl, Bing Xinyu, Laurence Arian, Lee Chyi-Chia R, Chapelle Dawn, Clarke Gillian I, Ohson Kamal, Nicholson Marc, Gadina Massimo, Yang Barbara, Korman Benjamin D, Gregersen Peter K, van Hagen P Martin, Hak A Elisabeth, Huizing Marjan, Rahman Proton, Douek Daniel C, Remmers Elaine F, Kastner Daniel L, Goldbach-Mansky Raphaela
Аннотация
METHODS: We studied nine children from six families who had neonatal onset of sterile multifocal osteomyelitis, periostitis, and pustulosis. Response to empirical treatment with the recombinant interleukin-1-receptor antagonist anakinra in the first patient prompted us to test for the presence of mutations and changes in proteins and their function in interleukin-1-pathway genes including IL1RN.
RESULTS: We identified homozygous mutations of IL1RN in nine affected children, from one family from Newfoundland, Canada, three families from The Netherlands, and one consanguineous family from Lebanon. A nonconsanguineous patient from Puerto Rico was homozygous for a genomic deletion that includes IL1RN and five other interleukin-1-family members. At least three of the mutations are founder mutations; heterozygous carriers were asymptomatic, with no cytokine abnormalities in vitro. The IL1RN mutations resulted in a truncated protein that is not secreted, thereby rendering cells hyperresponsive to interleukin-1beta stimulation. Patients treated with anakinra responded rapidly.
CONCLUSIONS: We propose the term deficiency of the interleukin-1-receptor antagonist, or DIRA, to denote this autosomal recessive autoinflammatory disease caused by mutations affecting IL1RN. The absence of interleukin-1-receptor antagonist allows unopposed action of interleukin-1, resulting in life-threatening systemic inflammation with skin and bone involvement. (ClinicalTrials.gov number, NCT00059748.)