Antibodies to flagellin indicate reactivity to bacterial antigens in IBS patients

Abstract

One of the several possible causes of irritable bowel syndrome (IBS) is thought to be low-grade mucosal inflammation. Flagellin, the primary structural component of bacterial flagellae, was shown in inflammatory bowel disease patients to activate the innate and adaptive immunity. It has not yet been conclusively established if IBS patients show reactivity to luminal antigens. In 266 patients [112 IBS, 61 Crohn's disease (CD), 50 ulcerative colitis (UC) and 43 healthy controls (HC)], we measured antibodies to flagellin (FAB, types A4-Fla2 and Fla-X), anti-Saccharomyces cerevisiae antibodies (ASCA) (both ELISA), antipancreas antibodies (PAB) and perinuclear antineutrophil cytoplasmatic antibodies (p-ANCA) (both IF). All IBS patients had normal fecal calprotectin (mean 21 microg mL(-1), SD 6.6) and fulfilled the ROME II criteria. Frequencies of antibodies in patients with IBS, CD, UC and HC, respectively, are as follows (in per cent): antibodies against A4-Fla2: 29/48/8/7; antibodies against Fla-X: 26/52/10/7; ASCA: 6/59/0/2; p-ANCA: 0/10/52/0; and PAB: 0/28/0/0. Antibodies against A4-Fla2 and Fla-X were significantly more frequent in IBS patients than in HC (P = 0.004 and P = 0.009). Antibodies to A4-Fla2 and Fla-X were significantly more frequent in IBS patients with antecedent gastroenteritis compared to non-postinfectious IBS patients (P = 0.002 and P = 0.012). In contrast to ASCA, PAB and p-ANCA, antibodies against A4-Fla2 and Fla-X were found significantly more often in IBS patients, particularly in those with postinfectious IBS, compared to HC. This observation supports the concept that immune reactivity to luminal antigens has a putative role in the development of IBS, at least in a subset of patients.

Review article: associations between immune activation, intestinal permeability and the irritable bowel syndrome

“…[49][50][51][52] However, most studies found no difference in the faecal levels of calprotectin and lactoferrin between IBS patients and healthy controls. 43,44,49,50,[52][53][54][55][56][57][58][59] Only one publication reported that increased levels of faecal calprotectin were correlated with pain severity; however, this result was observed in children displaying both functional abdominal pain and IBS. 60 Key point: (i) Typically, no changes in the levels of the faecal inflammatory markers calprotectin and lactoferrin are reported in IBS patients.…”

“…42 The potential activation of the innate gut immune system in IBS could be a sign of previous infection and/or ongoing low-grade inflammation. In this regard, increased faecal levels of the human beta-defensin HBD2, 43 an antimicrobial peptide produced by intestinal epithelial cells, and elevated blood concentrations of the A4-Fla2 and Fla-X bacteria-specific antibodies 44 38,46 Similarly, the Studies identified in PubMed literature search with the following key words:…”

Immune Activation in Irritable Bowel Syndrome: Can Neuroimmune Interactions Explain Symptoms?

“…Rectal infusion of fecal supernatants from IBS patients sensitizes mice to colorectal distension, which is suggested to occur via microbesecreted serine proteases, which activate protease-activated receptor-2 on nerve endings ( 16 -18 ). Th e direct eff ects on sensory nerves may also be compounded by activation of the innate and adaptive immune responses, as suggested by the elevated levels of antibodies against bacterial fl agella in IBS patients ( 19,20 ). Oral probiotic preparations aimed at restoring the " healthy commensal biota balance " have been met with much enthusiasm by IBS patients, and studies have shown Lactobacilli and Bifi dobacteria preparations both modulate immune function and improve IBS symptoms ( 21 -23 ).…”

Extracellular proteins secreted by probiotic bacteria as mediators of effects that promote mucosa–bacteria interactions

“…As previously stated, current knowledge about the interaction between extracellular proteins and the GALT mainly derives from data involving commensal bacterial groups. In this context, it has been observed that some proteins secreted by the commensal microbiota might be responsible for the anomalous immune response observed in the framework of inflammatory bowel disease (Adams et al, 2008;Ivison & Steiner, 2008;Schoepfer et al, 2008).…”