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The phosphorycholine moiety of the filarial nematode immunomodulator ES-62 is responsible for its anti-inflammatory action in arthritis
  1. Margaret M Harnett
  1. University of Glasgow, United Kingdom
    1. Dorothy E Kean
    1. University of Glasgow, United Kingdom
      1. Agnes Boitelle
      1. University of Strathclyde, United Kingdom
        1. Stephen McGuiness
        1. University of Strathclyde, United Kingdom
          1. Theresa Thalhamer
          1. University of Glasgow, United Kingdom
            1. Christina N Steiger
            1. University of Glasgow, United Kingdom
              1. Caitlin Egan
              1. University of Strathclyde, United Kingdom
                1. Lamyaa Al-Riyami
                1. University of Strathclyde, United Kingdom
                  1. Marcos J Alcocer
                  1. University of Nottingham, United Kingdom
                    1. Katrina M Houston
                    1. University of Strathclyde, United Kingdom
                      1. J Alastair Gracie
                      1. University of Glasgow, United Kingdom
                        1. Iain B McInnes
                        1. University of Glasgow, United Kingdom
                          1. William Harnett (w.harnett{at}strath.ac.uk)
                          1. University of Strathclyde, United Kingdom

                            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 IFNγ 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.

                            • antibody
                            • collagen-induced arthritis
                            • nematode
                            • phosphorylcholine
                            • synovial tissue

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