Infectious Serologies and Autoantibodies in Inflammatory Bowel Disease

Abstract

The aim of this study was to reevaluate the role of infection in inflammatory bowel disease (IBD). Sera from 119 patients with IBD [80 with Crohn's disease (CD); 39 with ulcerative colitis] and 98 healthy controls were assessed using the Bio-Rad BioPlex 2200 for the presence of Toxoplasma gondii, cytomegalovirus, Epstein-Barr virus, Treponema pallidum, and Saccharomyces cerevisiae. Hepatitis B virus, hepatitis C virus (HCV), and anti-Helicobacter pylori antibodies were assessed by ELISA. In addition, sera were tested for a panel of antibodies associated with thrombophilia as well as various autoantibodies. Titers of antibodies toward HCV and T. gondii, and S. cerevisiae were higher in IBD patients than in controls, while the H. pylori autoantibodies were less prevalent among the patient population. Several thrombophilia-associated antibodies were more common in CD patients, and a single patient had a thromboembolic event. Our results show an excess of anti-HCV and anti-T. gondii antibodies among patients with IBD compared to healthy controls. Whereas the former may be the result of immunosuppression from the inflammatory disease itself or from the medications used to treat it, the latter association suggests that T. gondii is involved in the etiopathogenesis of IBD, and especially CD, in humans, as has been shown in the murine model. However, our findings also reiterate the positive association between CD and anti-S. cerevisiae antibodies as well as the negative association with H. pylori infections. These, in turn, lend indirect support to the "hygiene hypothesis" in IBD as well as the newly proposed role of commensal bacteria in the initiation of the disease process.

Infections and autoimmunity – friends or foes?

“…Second, we found a lower prevalence of antihepatitis B antibodies among patients with MS and SLE [6]. Third, we detected a low prevalence of H. pylori seropositivity among patients with IBD [10], which is in agreement with other studies that showed that H. pylori seropositivity was associated with late presentation of IBD [81].…”

“…In recent years, the compound interplay between infections and autoimmunity has been studied extensively. Here, we summarize the current literature and preliminary results from our international study on this issue [4][5][6][7][8][9][10][11][12][13] (Figure 1). The versatile interactions of ADs with different infectious agents, the burden of infections from childhood to adulthood, immune and genetic mechanisms, and the possibility that infections also confer protection from autoimmunity are also discussed (Box 1).…”

Pathogenesis of Crohn’s disease: Bug or no bug

“…Despite the association between the intensity of expression in the intestinal mucosa and the severity of the IBD inflammation, viral replication was also found in healthy mucosa [96] . A higher CMV infection rate was not observed in the IBD population with respect to the general population [97] .…”

Role of childhood infection in the sequelae of H. pylori disease

“…98 Interestingly, H. pylori DNA suppresses the production of IL-12 and type 1 IFN by mouse bone marrow-derived DCs and human plasmacytoid DCs and attenuates the severity of the inflammatory response in dextran sodium sulfate-induced colitis, 99 suggesting a partial explanation for the inverse association between H. pylori infection and inflammatory bowel disease. [100][101][102] To dissect the interaction between DCs and Tregs, investigators have elegantly shown that H. pylori reprogram DCs to a tolerance-promoting phenotype in an IL-18-dependent manner, thereby promoting Tregs and suppressing effector T cell function. 103 Subsequently, H. pylori γ-glutamyl transpeptidase and VacA were shown to drive the DC-induced Treg skewing.…”