title: The phosphorycholine moiety of the filarial nematode immunomodulator ES-62 is responsible for its anti-inflammatory action in arthritis.
abstract: OBJECTIVE
  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.
  
  
  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 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-gamma from human patient tissues could be mimicked by OVA-PC but not rES-62 or ovalbumin.
  
  
  CONCLUSIONS
  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.
authors: Division of Immunology, Infection and Inflammation, Glasgow Biomedical Research Centre, University of Glasgow, Glasgow, UK.
authors: M M
authors: MM
authors: Harnett
authors: D E
authors: DE
authors: Kean
authors: A
authors: A
authors: Boitelle
authors: S
authors: S
authors: McGuiness
authors: T
authors: T
authors: Thalhamer
authors: C N
authors: CN
authors: Steiger
authors: C
authors: C
authors: Egan
authors: L
authors: L
authors: Al-Riyami
authors: M J
authors: MJ
authors: Alcocer
authors: K M
authors: KM
authors: Houston
authors: J A
authors: JA
authors: Gracie
authors: I B
authors: IB
authors: McInnes
authors: W
authors: W
authors: Harnett
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000097:blood; D015801:Helminth Proteins / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007155:Immunologic Factors / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use*; D018836:Inflammation Mediators / Q000097:blood; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D010767:Phosphorylcholine / Q000276:immunology*; D011994:Recombinant Proteins / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use; D013583:Synovial Membrane / Q000276:immunology; D046509:Tissue Culture Techniques
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; C435884:ES-62 protein, Acanthocheilonema viteae; D015801:Helminth Proteins; D007074:Immunoglobulin G; D007155:Immunologic Factors; D018836:Inflammation Mediators; D011994:Recombinant Proteins; D010767:Phosphorylcholine