Background Autoimmune diseases are characterized by tissue damage and loss of function due to an immune response that is directed against specific organs. The role of impaired intestinal barrier function on autoimmune pathogenesis is widely discussed now. Together with the gut-associated lymphoid tissue and the neuroendocrine network, the intestinal epithelial barrier, with its intercellular tight junctions, controls the equilibrium between tolerance and immunity to non-self antigens.
Pancreatic zymogen granule protein 2 Glycoprotein 2 (GP2) has been identified as a major autoantigenic target of the so-called pancreatic antibodies. Recent studies have demonstrated that GP2 is expressed on the apical surface of intestinal membranous cells of the follicle-associated epithelium, and is essential for host-microbial interaction and the initiation of bacteria-specific mucosal immune responses. Antibodies to GP2 have demonstrated diagnostic significance for Crohn's disease. Anti-GP2 autoantibodies are detected in 25–30% of patients with CD and in 5–12% of patients with UC. They potentially may be produced in patients with rheumatic disease and be one of missing link between gut inflammation and development the systemic autoimmune process. The aim of our work to study prevalence of anti GP2 antibody in patients with rheumatic diseases.
Objectives We studied 163 persons: 87 patients with spondyloarthropathies (SpA) (64 patients with ankylosing spondylitis (AS), 23 – with psoriatic arthritis (PsA)), 66 patients with inflammatory arthritis (IA) (47 patients with rheumatoid arthritis (RA), 19 patients with unclassified arthritis (UA)). As healthy controls 160 adult blood donors were included. All patients are fulfilled respective latest classification criteria.
Methods Levels of anti-GP2 antibodies (IgA and IgG classes) have been detected by ELISA, employing recombinant human GP2 (Medipan GmbH, Germany). Cut-off levels, determined by manufactures, are ≥20 U/ml
Results Anti-GP2 IgA were more prevalent in SpA (39/87, 44.82%) than in IA (11/66, 22.72%) patients (p=0.009) and in controls (6/160, 3.75%) (p<0.001). In subgroups, PsA patients showed a significantly higher prevalence of anti-GP2 IgA (13/23, 56.52%) in comparison with RA patients (12/47, 25.53%, p=0.02) and UA patients (3/19, 15.78%, p=0.02), whereas AS patients did not reveal a significant prevalence for these autoantibody specificities (26/64, 40.65%, p=0.3).
Anti-GP2 IgG were more prevalent in SpA (17/87, 19.54%) and IA (9/66, 13.63%) patients than in controls (4/160, 2.5%) (p<0.001). In subgroups, PsA patients showed a significantly higher prevalence of anti-GP2 IgG (9/23, 37.5%) in comparison with AS patients (8/64, 12.5%, p=0.019) and whereas RA and UA patients did not show a significant prevalence for these autoantibody specificities (7/47, 14.89%; 2/19, 10.52%, p>0.05 respectively).
Conclusions Anti-GP2 antibodies, considering as a novel CD-specific markers, are found to be positive in about 35% of patients with rheumatic diseases. Moreover, the highest prevalence anti-GP2 IgA was observed in PsA patients.
These data may be additional steps in understanding several interrelationships between gut inflammation and the development of autoimmune diseases. It is necessary to continue study in this direction for finding new data.
Disclosure of Interest M. Volkava: None declared, A. Kundzer: None declared, I. Generalov: None declared, D. Roggenbuck Shareholder of: GA Generic Assays GmbH and Medipan GmbH, D. Petrovich: None declared