The phosphorycholine moiety of the filarial nematode immunomodulator ES-62 is responsible for its anti-inflammatory action in arthritis

M.M. Harnett, Dorothy E. Kean, A. Boitelle, S. McGuiness, T. Thalhamer, C.N. Steiger, Caitlin Egan, Lamyaa Al-Riyami, Marcos J.C. Alcocer, Katrina M. Houston, J.A. Gracie, I.B. McInnes, W. Harnett

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Abstract

In countries where parasitic infections are endemic, autoimmune disease is relatively rare, leading to the hypothesis that parasite-derived immunomodulators may protect against its development. Consistent with this, we have previously demonstrated that ES-62, a 62 kDa phosphorylcholine (PC)-containing glycoprotein that is secreted by filarial nematodes, can exert anti-inflammatory action in the murine collagen-induced arthritis (CIA) model and human rheumatoid arthritis-derived synovial tissue cultures. As a first step to developing ES-62-based drugs, the aim of this study was to determine whether the PC-moiety of ES-62 was responsible for its anti-inflammatory actions. We compared the anti-inflammatory activity of a PC-free form of recombinant ES-62 (rES-62) and a synthetic PC-ovalbumin conjugate (OVA-PC) with that of native ES-62 in the CIA model and synovial tissues from patients with rheumatoid arthritis. Results: The anti-inflammatory actions of ES-62 in CIA appear to be dependent on the PC moiety as indicated by the reduction in severity of disease and also suppression of collagen-specific T helper 1 cytokine production observed when testing OVA-PC, but not rES-62. Interestingly, the anti-inflammatory activity of PC did not correlate with a reduction in anti-collagen IgG2a levels. Also, the ES-62-mediated suppression of interferon- from human patient tissues could be mimicked by OVA-PC but not rES-62 or ovalbumin. In countries where filariasis is endemic the reduced detection of inflammatory diseases, such as rheumatoid arthritis may be because of the anti-inflammatory action of the PC moieties of ES-62. PC may thus provide the starting point for the development of novel, safe immunomodulatory therapies.
Original languageEnglish
Pages (from-to)518-523
Number of pages6
JournalAnnals of the Rheumatic Diseases
Volume67
Issue number4
Early online date17 Aug 2007
DOIs
Publication statusPublished - 2008

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Keywords

  • phosphorycholine moiety
  • filarial nematode
  • immunomodulator
  • anti-inflammatory action
  • arthritis
  • pharmacology
  • biomedical sciences

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