ES-62 prevents development of lupus-like pathology in the MRL/Lpr mouse (P5210)

The prevalence of autoimmunity in developing countries is lower than that in the developed world and this inverse relationship correlates with the level of chronic parasitic infections. Co-evolution of parasites with the human immune system has resulted in evasion strategies that prevent the host clearing the parasite yet limit pathology. One mechanism involves the release of immunomodulators like ES-62, secreted by the filarial nematode Acanthocheilonema viteae: ES-62 exhibits broad anti-inflammatory activity and therapeutic potential in autoimmune diseases such as rheumatoid arthritis. Here we show that ES-62 protects against nephritis, as indicated by proteinuria levels, in the murine MRL/Lpr model of systemic lupus erythematosus (SLE). It has been proposed that the pro-inflammatory cytokine IL-17 is a primary driver of disease, in mouse models as well as in SLE patients, but our data do not support targeting of IL-17 as the major protective mechanism underlying ES-62 efficacy. Indeed, and consistent with this, we have shown that neutralising antibodies specific for IL-17 do not block development of proteinuria. ES-62 is a large immunogenic glycoprotein and therefore not suitable for therapeutic use. Thus, since the active moiety of ES-62 is phosphorylcholine (PC), we have recently developed small molecular analogues based around PC that mimic the immunomodulatory effects of ES-62 in autoimmune disorders, including SLE.