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

Harnett, M.M. and Kean, Dorothy E. and Boitelle, A. and McGuiness, S. and Thalhamer, T. and Steiger, C.N. and Egan, Caitlin and Al-Riyami, Lamyaa and Alcocer, Marcos J.C. and Houston, Katrina M. and Gracie, J.A. and McInnes, I.B. and Harnett, W. (2008) The phosphorycholine moiety of the filarial nematode immunomodulator ES-62 is responsible for its anti-inflammatory action in arthritis. Annals of the Rheumatic Diseases, 67 (4). pp. 518-523. ISSN 0003-4967 (https://doi.org/10.1136/ard.2007.073502)

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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.

ORCID iDs

Harnett, M.M., Kean, Dorothy E., Boitelle, A., McGuiness, S., Thalhamer, T., Steiger, C.N., Egan, Caitlin, Al-Riyami, Lamyaa, Alcocer, Marcos J.C., Houston, Katrina M., Gracie, J.A., McInnes, I.B. and Harnett, W. ORCID logoORCID: https://orcid.org/0000-0001-9545-9401;
CORE (COnnecting REpositories)