Abstract
BackgroundDevelopment of inflammatory bowel disease (IBD) involves the interplay of environmental and genetic factors with the host immune system. Mechanisms contributing to immune dysregulation in IBD are not fully defined. Development of novel therapeutic strategies is focused on controlling aberrant immune response in IBD. Current IBD therapy utilizes a combination of immunomodulators and biologics to suppress pro-inflammatory effectors of IBD. However, the role of immunomodulatory factors such as annexin A1 (ANXA1) is not well understood. The goal of this study was to examine the association between ANXA1 and IBD, and the effects of anti-TNF-α, Infliximab (IFX), therapy on ANXA1 expression.MethodsANXA1 and TNF-α transcript levels in PBMC were measured by RT PCR. Clinical follow up included the administration of serial ibdQs. ANXA1 expression in the gut mucosa was measured by IHC. Plasma ANXA1 levels were measured by ELISA.ResultsWe found that the reduction in ANXA1 protein levels in plasma coincided with a decrease in the ANXA1 mRNA expression in peripheral blood of IBD patients. ANXA1 expression is upregulated during IFX therapy in patients with a successful intervention but not in clinical non-responders. The IFX therapy also modified the cellular immune activation in the peripheral blood of IBD patients. Decreased expression of ANXA1 was detected in the colonic mucosa of IBD patients with incomplete resolution of inflammation during continuous therapy, which correlated with increased levels of TNF-α transcripts. Gut mucosal epithelial barrier disruption was evident by increased plasma bacterial 16S levels.ConclusionLoss of ANXA1 expression may support inflammation during IBD and can serve as a biomarker of disease progression. Changes in ANXA1 levels may be predictive of therapeutic efficacy.
Highlights
Inflammatory bowel disease (IBD) is a debilitating disorder characterized by severe inflammation of the gastrointestinal tract, often leading to physical symptoms of abdominal pain and recurrent diarrhea [1,2]
We investigated the role of annexin A1 (ANXA1) associated anti-inflammatory processes in the development of inflammatory bowel disease (IBD) and during IFX therapy
We report a substantial loss of ANXA1 expression in the colonic mucosal and peripheral blood compartments from patients with progressive IBD, Crohns Disease
Summary
Inflammatory bowel disease (IBD) is a debilitating disorder characterized by severe inflammation of the gastrointestinal tract, often leading to physical symptoms of abdominal pain and recurrent diarrhea [1,2]. One of the mechanisms of IBD includes the breakdown of gut homeostasis that may be induced by dysfunction in mucosal immunity [2,3,4]. Both human and murine studies suggest that several genetic defects in innate immunity and aberrant T-cell activation play a critical role in the pathogenesis of IBD [5,6]. Decreased expression of ANXA1 was detected in the colonic mucosa of IBD patients with incomplete resolution of inflammation during continuous therapy, which correlated with increased levels of TNF-α transcripts. Changes in ANXA1 levels may be predictive of therapeutic efficacy
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