P68 A diet rich in wheat alpha-amylase/trypsin inhibitors (ATIs) enhances disease progression in the MRL-Fas(lpr) mouse model of systemic lupus erythematosus

Background Wheat alpha-amylase/trypsin inhibitors (ATIs) are the second most prevalent proteins in wheat (3–4% vs 80–90% for gluten) and potent activators of the innate immune system via the toll like receptor 4 (TLR4)-MD2-CD14 complex in cells of the mononuclear phagocyte system (Junker Y et al, J Exp Med 2012), triggering several autoimmune/inflammatory diseases. In contrast, pure gluten that is de-enriched of ATIs shows no stimulatory activity. MRL-Fas(lpr) mice develop progressive and spontaneous glomerular, tubulointerstitial and perivascular kidney disease, arthritis, lymphadenopathy, splenomegaly and circulating autoantibodies in a syndrome that resembles systemic lupus erythematosus (SLE). Here we explored the effect of dietary ATIs on disease severity in MRL-Fas(lpr) mice. Methods MRL-Fas(lpr) mice were placed either on a gluten-free diet (GFD) or a diet containing 25% gluten (which contains amounts of ATIs equivalent to the human wheat based diet). We measured serum cytokines, proteinuria, haematuria, hemoglobinuria and histological and immunohistochemical markers of myeloid inflammation (F4/80 and CD68) in different affected organs (kidney, spleen and intestine). Results Mice on a GFD showed lower levels of serum inflammatory cytokines (IL-6, KC and TNFa) that accompanied lower grade proteinuria, haematuria and hemoglobinuria during the study period. CD68, F4/80 and CD4 positive cells were also higher in the animals that consumed ATIs. Conclusions Dietary wheat ATIs enhances SLE disease progression, in contrast, a GFD (which is ATI-free) had a protective effect on the development of SLE in MRL-Fas(lpr) mice, confirming the role of ATIs as important nutritional co-stimulant of inflammation in autoimmune diseases.