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

Margaret M Harnett ¹, Dorothy E Kean ¹, Agnes Boitelle ², Stephen McGuiness ², Theresa Thalhamer ¹, Christina N Steiger ¹, Caitlin Egan ², Lamyaa Al-Riyami ², Marcos J Alcocer ³, Katrina M Houston ², J Alastair Gracie ¹, Iain B McInnes ¹ and William Harnett ^2*

¹ University of Glasgow, United Kingdom
² University of Strathclyde, United Kingdom
³ University of Nottingham, United Kingdom

^* To whom correspondence should be addressed. E-mail: w.harnett{at}strath.ac.uk.

Accepted 22 July 2007

Abstract

Objective: In countries endemic for parasitic infections, 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 62kDa 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 (RA)-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.

Methods: 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 RA patients.

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 Th1 cytokine production observed when testing OVA-PC, but not rES-62. Interestingly, PC's anti-inflammatory activity did not correlate with a reduction in anti-collagen IgG2a levels. Also, the ES-62-mediated suppression of IFN from human patient tissues could be mimicked by OVA-PC but not rES-62 or ovalbumin.

Conclusion: A cause of the reduced detection of inflammatory diseases, such as RA, in countries endemic for filariasis may be the anti-inflammatory action of the PC moieties of ES-62. PC may thus provide the starting point for development of novel, safe immunomodulatory therapies.

Keywords: antibody, collagen-induced arthritis, nematode, phosphorylcholine, synovial tissue

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