Production of immunoglobulin G and G1 antibodies to cytoskeletal protein by lamina propria cells in ulcerative colitis.

Abstract

Recent studies suggest an autoantigenic role for tropomyosin-related protein(s) in ulcerative colitis (UC). This study examined whether immunoglobulin G and G1 subclass antibodies against tropomyosins are produced spontaneously by the lamina propria mononuclear cells (LPMCs) that infiltrate the inflamed UC tissue. LPMCs were isolated from colonic biopsy specimens from 29 patients with UC, 15 with colonic Crohn's disease (CD), and 13 with non-inflammatory bowel disease (IBD). The autologous peripheral blood mononuclear cells (PBMCs) were obtained. Cells were cultured in vitro and unstimulated for 10 days. Spontaneous production of immunoglobulin G and G1 antibodies against tropomyosins was measured by enzyme-linked immunosorbent assays using highly enriched tropomyosins from skeletal muscle and colonic mucosa. The total immunoglobulin G produced by LPMCs from both patients with UC and CD was comparable but higher than from patients with non-IBD (P < 0.05). However, immunoglobulin G antibodies to tropomyosins were higher in patients with UC than in patients with CD (P < 0.04) and non-IBD (P < 0.02). LPMCs from patients with symptomatic UC produced higher immunoglobulin G antibodies to tropomyosins than patients with UC in remission (P < 0.03), symptomatic CD (P < 0.04), and non-IBD (P < 0.02). Immunoglobulin G antibodies to tropomyosins predominantly belonged to immunoglobulin G1 subclass. The autologous PBMCs showed comparable results. Immunoglobulin G antibodies predominantly belonging to immunoglobulin G1 subclass and reactive against tropomyosin-related protein(s) are spontaneously produced by LPMCs from the colonic mucosa in patients with UC.