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

Natalie Frede,Wolfgang Kreisel,Erik-Oliver Glocker,Frank M Ruemmele,Bodo Grimbacher,Jennifer Wanders,Karin R Engelhardt

doi:10.1186/1471-2172-15-10

Abstract

BackgroundInflammatory 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.ResultsThirteen 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.ConclusionNo evidence for an involvement of autoantibodies against IL-10 or IL-10R in the pathogenesis of inflammatory bowel disease could be established.

Highlights

Inflammatory bowel disease constitutes a heterogeneous group of conditions, whose aetiology is only partly understood
Antibodies against IL-10 Antibodies of the IgG isotype Sera of 20 healthy donors as well as 52 Inflammatory bowel disease (IBD) patients were subjected to Enzyme-linked immunosorbent assay (ELISA) testing in search of anti-IL10 IgG antibodies
We found the Crohn’s disease (CD) group to exhibit significantly elevated levels of anti-IL-10 IgG antibodies, whereas the ulcerative colitis (UC) group testing resulted in a non-significant p-value (p = 0.41)

Summary

Introduction

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. 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. IBD is considered as the result of an excessive and inadequate immune response to commensals of the intestine, defining IBD as a pro-inflammatory disorder [2]. An autoimmune background has been suggested for IBD, and antibodies against numerous auto-antigens have been detected [14,15,16,17,18]. In 2009, Ebert et al described autoantibodies against various cytokines in IBD patients leading to a state of relative deficiency of IL2, TGF-β and IL-10 [19]. Given the relevance of IL-10 as the key immunomodulatory factor of the human immune system, neutralizing autoantibodies against IL-10

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