Z Gastroenterol 2016; 54 - KV051
DOI: 10.1055/s-0036-1586827

Disease progression in murine systemic lupus erythematosus induced by consumption of amylase trypsin inhibitor (ATIs)

V Zevallos 1, J Weinmann-Menke 2, M Meineck 2, D Schuppan 1
  • 1Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Institut für Translationale Immunologie, Mainz, Deutschland
  • 2Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Department of Nephrology and Rheumatology, Mainz, Deutschland

Background and aims: Wheat alpha-amylase/trypsin inhibitors (ATIs) are activators of the innate immune system via the toll like receptor 4 (TLR4)-MD2-CD14 complex in cells of the mononuclear phagocyte system, triggering several autoimmune/inflammatory diseases. MRL-Faslpr mice, develops progressive and expontaneous glomerular, tubulointerstitial, perivascular kidney disease, arthritis, lymphadenopathy, splenomegaly and circulating autoantibodies that resembles systemic lupus erythematosus (SLE). We explored the effects of dietary ATIs in the development of progressive SLE using the MRL-Fas(lpr) mouse model.

Methods: MRL-Faslpr mice were fed with a gluten/ATI-free diet for 4 weeks and thereafter divided in 2 groups: 1) continue with the GFD/ATI-free diet, 2) changed to a diet containing gluten (25% crude protein, CP), containing amounts of ATIs equivalent to the human wheat based diet). We measured clinical parameters such as proteinuria, haematuria, hemoglobinuria and serum inflammatory chemokine/cytokine levels throughout the experiment. At sacrifice, myeloid inflammatory cells were quantified immunohistochemically in the intestine, kidneys and spleen.

Results: Mice on a GFD showed significantly attenuated clinical parameters of kidney dysfunction (proteinuria, haematuria, hemoglobinuria) and serum inflammatory cytokines (IL-6, KC and TNFα) compared to mice on a gluten (and ATI) containing diet. Gluten/ATI-fed mice also showed a significant increase in kidney infiltrating CD4+ T cells producing IL-12 and IL-17, in line with patients with SLE and the worsened clinical course. Furthermore, intestinal CD68+ and F4/8+ myeloid cells and CD4+ T cells were mildly increased in the intestine of mice ingesting ATIs.


  • Nutritional wheat ATIs exacerbate experimental SLE compared to an ATI-free diet;

  • Disease progression is mediated by intestinal innate and (secondary) adaptive immune activation;

  • Further studies are needed to determine the mechanism by which dietary ATIs enhance extraintestinal manifestations of SLE.