Background:The search for new methods for predicting the effectiveness of treatment for biologics is important issue.Objectives:To study antinuclear antibodies (ANA) levels during of AS treatment by infliximab and evaluate the influence of ANA on treatment outcomeMethods:The presence of antinuclear antibodies (ANA) in 53 ankylosing spondylitis (AS) patients (44 men (83.02%), and 9 women (16.98%), 37.19 ± 9.38 years (95% CI: 34.60-39.78) treated with infliximab was determined by indirect immunofluorescence on an automated AKLIDES system in a serum titer of 1/80 initially (before treatment with infliximab) and at week 30 (before 7 administration). Specific autoantibodies were analyzed on the AKLIDES Cytobead platform using the following antigens SS-A 52, SS-A 60, SS-B, ds-DNA, CENP-B, Sm, RNP / Sm. ANA research was carried out at the Brandenburg Technical University (Senftenberg, Germany). Evaluation of the effectiveness of infliximab therapy was carried out by determining ASDAS-CRP at baseline, at the 14th, 30th and 54th weeks.Results:A positive nuclear type of ANA was determined initially in 2 out of 53 patients (3.77%) (in one case, the type of luminescence was nucleolar, in the other - speckled), at the 30th week of observation, 16 out of 53 patients became seropositive for ANA (30.18%). The frequency of occurrence of ANA at the 30th week of treatment was significantly higher than the baseline (p <0.0001). Positive results for the determination of specific autoantibodies to at least one nuclear antigen were found in 7 of 16 (43.75%) ANA-positive patients. In all cases, Anti-SS-A 60 (100%) was detected.In the group of patients in whom treatment with infliximab was ineffective at the 54th week of observation, ANA positivity was observed in 10 (55.5%). In the case of treatment effectiveness at the 54th week of ANA, positivity was not observed at the 30th week. Differences in the incidence of ANA in patients with effective and ineffective treatment at week 54 were statistically significant (p <0.0001). Anti-infliximab antibodies were significantly more common in ANA-positive patients at week 30 of treatment with infliximab (p = 0.002, Fisher’s exact test).The appearance of ANA at the 30th week of infliximab therapy was inversely related to the absence of secondary resistance at the 54th week of treatment according to the ASDAS-CRP criteria (OR 0.026; 95% CI: 0.002-0.039; p = 0.0007), which allows us to use the results of the determination of ANA at the 30th week of treatment with infliximab as a predictor of secondary resistance to treatment at the 54th week. When testing the method for predicting secondary resistance to treatment with infliximab at week 54 based on the results of determining ANA at week 30 of treatment in a control sample of 12 patients with AS, it was found that the method is statistically significant (p = 0.0015, Fisher’s exact test).Conclusion:Assessment of ANA positivity at week 30 of treatment with infliximab can be seen a predictor of the development of secondary resistance to infliximab at the 54th week of treatment.Disclosure of Interests:None declared
Background and objectivesAutoimmune diseases are characterised by tissue damage and loss of function due to an immune response that is directed against specific organs. 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. 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. There are certain relationships in pathgenesis and clinical course of inflammatory bowel diseases and spondyloarthropathies.The aim of our study is to investigate the prevalence of anti-GP2 in patients with SpA and evaluate the potential impact in relationships between gut inflammation and development the systemic autoimmune process.Materials and methodsWe studied 87 patients with SpA (64 patients with ankylosing spondylitis (AS), 23 – with psoriatic arthritis (PsA). As healthy controls 160 adult blood donors were included. All patients are fulfilled respective latest classification criteria.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.ResultsAnti-GP2 IgA were more prevalent in SpA (39/87, 44.82%) in controls (6/160, 3.75%) (p < 0.001). PsA patients did not reveal a significant prevalence prevalence of anti-GP2 IgA (13/23, 56.52%) in comparison with AS patients (26/64, 40.65%, p = 0.3).Anti-GP2 IgG were more prevalent in SpA (17/87, 19.54%) patients than in controls (4/160, 2.5%) (p < 0.001). 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).ConclusionsAnti-GP2 antibodies, considering as a novel CD-specific markers, are found to be positive in about 44% of patients with SpA. Moreover, the highest prevalence anti-GP2 IgA was observed in PsA patients. These data may help to find new interrelationships between gut inflammation and the development of autoimmune diseases.
BackgroundAutoimmune 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.ObjectivesWe 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.MethodsLevels 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/mlResultsAnti-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).ConclusionsAnti-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-G...
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