Abstract
BackgroundGlycoprotein 2 (GP2) was discovered as the major autoantigen of Crohn’s disease (CD)-specific pancreatic autoantibodies (PAB). We investigated anti-GP2 IgA and IgG antibodies as novel serological parameters in CD and assessed their association with distinct disease phenotypes.MethodsAnti-GP2 and anti-Saccharomyces cerevisiae (ASCA) IgA and IgG were detected by ELISA employing recombinant human GP2 and phosphopeptidomannan, respectively and PAB by indirect immunofluorescence (IIF) in 271 sera, 169 with CD and 102 with ulcerative colitis (UC). As healthy controls 160 adult blood donors and 65 children were included.ResultsAnti-GP2 IgG and/or IgA were more prevalent in CD (51/169, 30.2%) than in UC (9/102, 8.9%) patients and in controls (9/225, 4%) (p < 0.001 respectively). ASCA IgG and/or IgA were present in 60/169 (35.5%) in CD and in 7/102 (6.9%) in UC patients (p < 0.001). CD patients with ileocolonic location (L3) showed a significantly higher prevalence of anti-GP2 and ASCA IgA and/or IgG (40/113 and 48/113, respectively; p < 0.05 for both comparisons), whereas CD patients with colonic location (L2) revealed a significantly diminished prevalence for these autoantibody specificities (2/32 and 5/32, respectively, p < 0.05 for both). Anti-GP2 IgG were significantly more prevalent in CD patients with stricturing behaviour (B2) and perianal disease (7/11, p < 0.02) and less prevalent in those with penetrating behaviour (B3) and perianal disease (4/31, p < 0.05). The occurrence of anti-GP2 IgA and/or IgG was significantly more prevalent in CD patients with age at diagnosis of ≤16 years (16/31, p < 0.009). Prevalence of one or more anti-GP2 or ASCA IgA and/or IgG was significantly higher in L3, B2, and A1 and lower in L2 (68/113, 27/41, 23/31, 6/32; p < 0.04, respectively).ConclusionsAnti-GP2 IgG and IgA, constituting novel CD specific autoantibodies, appear to be associated with distinct disease phenotypes identifying patients at a younger age, with ileocolonic location, and stricturing behaviour with perianal disease.
Highlights
Glycoprotein 2 (GP2) was discovered as the major autoantigen of Crohn’s disease (CD)-specific pancreatic autoantibodies (PAB)
Patient cohorts To investigate humoral autoreactivity to GP2 in inflammatory bowel disease (IBD), 271 patients with IBD (169 CD patients, 102 ulcerative colitis (UC) patients) and 225 controls were included into this multicentre study with one British and two German gastroenterology departments
Comparison of antibodies to GP2 with PAB in IBD patients and controls Recombinant human GP2 immobilised on microtiter plates was employed to detect anti-GP2 IgG and IgA antibodies in sera of 169 patients with CD, 102 patients with UC and 225 controls (Table 2)
Summary
Glycoprotein 2 (GP2) was discovered as the major autoantigen of Crohn’s disease (CD)-specific pancreatic autoantibodies (PAB). The pathophysiology of IBD is poorly understood, there is scientific evidence demonstrating that a damaged mucosal barrier is leading to mucosal inflammation triggered by intestinal bacteria in genetically predisposed individuals [3,5]. Immune responses to disease-specific autoantigens appear to be a prominent feature of CD, and are possibly involved in the pathogenesis of IBD [3]. Glycoprotein 2 (GP2) has recently been identified as the major autoantigenic target of CD-specific pancreatic autoantibodies (PAB) [6,7,8]. GP2 has been demonstrated to be a membrane-anchored receptor of microfold cells (M cells) in human intestinal Peyer’s patches (PP) and to be over-expressed at the site of CD inflammation in contrast to UC [6,11]. GP2 interacts with epithelial and activated T cells, binds to scavenger receptor on endothelial cells, and modulates innate and adaptive immune responses supporting a potential pathophysiological role [2,12]
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