Evidence for non-neutralizing autoantibodies against IL-10 signalling components in patients with inflammatory bowel disease

BACKGROUND: Inflammatory bowel disease constitutes a heterogeneous group of conditions, whose aetiology is only partly understood. The prevailing hypothesis on its pathogenesis is that IBD is the result of an inadequate immune response to the resident bacterial flora of the intestine. An autoimmune background, however, has been discussed since the 1950s. Lately, it has been shown that failures in interleukin-10 (IL-10) signalling due to IL-10- and IL-10 receptor (IL-10R) mutations result in IBD. Our study aimed at investigating the existence of inhibitory autoantibodies against IL-10 and IL-10R in IBD patients capable of down-modulating IL-10 signalling thereby mimicking IL-10 or IL-10R deficiency. RESULTS: Thirteen IBD patients had IgG autoantibodies against IL-10, IL-10RA and/or IL-10RB, and three patients had IgA autoantibodies against IL-10. However, the absolute OD values of the serum antibodies measured by ELISA were low, there was overall no significant difference between patients and controls, and positive sera had no neutralizing activity. CONCLUSION: No evidence for an involvement of autoantibodies against IL-10 or IL-10R in the pathogenesis of inflammatory bowel disease could be established.