Suppression of collagen-induced arthritis with a serine proteinase inhibitor (serpin) derived from myxoma virus

Ernest Brahn, Sarah Lee, Alexandra Lucas, Grant McFadden, Colin MaCaulay

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Many viruses encode virulence factors to facilitate their own survival by modulating a host's inflammatory response. One of these factors, secreted from cells infected with myxoma virus, is the serine proteinase inhibitor (serpin) Serp-1. Because Serp-1 had demonstrated anti-inflammatory properties in arterial injury models and viral infections, it was cloned and evaluated for therapeutic efficacy in collagen-induced arthritis (CIA). Clinical severity was significantly lower in the Serp-1 protocols (p < 0.0001) and blinded radiographs indicated that the Serp-1 group had significantly less erosions than the controls (p < 0.01). Delayed-type hypersensitivity was lower in the Serp-1 group but antibody titers to type II collagen were not significantly altered. Recipients had minimal histopathologic synovial changes and did not develop neutralizing antibodies to Serp-1. These results indicate that Serp-1 impedes the pathogenesis of CIA and suggests that the therapeutic potential of serine proteinase inhibitors in inflammatory joint diseases, such as rheumatoid arthritis, should be investigated further.

Original languageEnglish (US)
Pages (from-to)254-263
Number of pages10
JournalClinical Immunology
Volume153
Issue number2
DOIs
StatePublished - Aug 2014
Externally publishedYes

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Keywords

  • Collagen arthritis
  • Immunotherapy
  • Myxoma
  • Rheumatoid
  • Serpin

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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