Soluble interleukin-1 receptor antagonist intron 2 polymorphism: Functional role and relevance in multiple sclerosis

F. L. Sciacca, K. Vandenbroeck, M. Marrosu, D. Franoiotta, M. Zaffaroni, G. Martino, L. M E Grimaldi

Research output: Contribution to journalArticle

Abstract

Soluble interleukin 1 receptor-antagonist (sIL-lra) antagonizes interleukin-1 (IL-1) by binding both IL1 receptors with comparable affinity, but failing to trigger any intracellular signal. The IL-lra gene is polymorphic: the intron 2 contains a 2 to 6 repeats of an 86 bp sequence. The A2 allele 12 repeats) has been associated with the occurence of autoimmune inflammatory disease. We analyzed the intron 2 allele frequency in 353 patients affected by multiple sclerosis (MS) and in 263 healthy controls (HO . Although no association was found with the occurence of MS, course of disease and sex, a significant increase of A2 frequency was found those MS patients with a particularly benign course of disease if e. at least 10 years from diagnosis and expanded disability status scale (EDSS) ≤3] compared to the remaining MS patients with aggressive course of disease (EDSS>3) (p=0.026). The functional role of this polymorphism on the sIL-lra expression was then investigated at mRNA and protein levels in myelomonocytic cell lines and in blood cells and sera from MS patients and healthy controls. The carriage of- A2 allele was significantly associated with higher levels of sIL-lra mRNA and mature protein. We conclude that IL-lra A2 allele is associated with an elevated production of sIL-lra which might determine relatively milder inflammation during autoimmune diseases. This allele seems to be a modifier of the natural hystory of MS.

Original languageEnglish
Pages (from-to)78
Number of pages1
JournalItalian Journal of Neurological Sciences
Volume18
Issue number4
Publication statusPublished - 1997

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology

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