Background Elastin is an ubiquitous molecule, presented in connective tissue matrix, including skin, ligaments, lungs, and blood vessels. Elastase is a characteristic protease, considerably presented in neutrophils and in pancreas. Autoantibodies (Ab) to elastin and to elastase are promising candidate biomarkers in rheumatoid arthritis (RA).
Objectives To explore potential clinical and diagnostic utility of anti-elastin and anti-elastase Ab in RA.
Methods The research was carried out in agreement with the WMA Declaration of Helsinki principles and was approved by Volgograd Regional Committee on Medical Ethics. All the patients signed the informed consent. We enrolled 106 adult patients with definite RA in Volgograd Municipal Hospital #25, the diagnosis have been established using ACR-EULAR criteria (2010). For ROC analysis calculations we used mixed control group consisted of 19 patients with ankylosing spondylitis, 32 with gout, 11 with psoriatic arthritis, and 22 with reactive arthritis. Serum anti-elastin and anti-elastase Ab concentrations were evaluated by ELISA, using antigens immobilized on magnetic polyacrylamide beads, which were previously described by our group . Antibody concentrations were expressed as relative optical density units (ODU). The cutoff values for anti-elastin and anti-elastase Ab presence were 0.104 and 0.113 ODU, respectively; the calculations were performed using 34 healthy control sera. All the means and operation characteristics were expressed as values (95% confidence intervals). Differences were considered significant when p<0.05.
Results In RA anti-elastin Ab were found in 37 (34.9%) patients, and the mean concentration was 0.128 (0.118–0.138) ODU. There was no significant correlation between DAS28 and anti-elastin concentrations, but the least marker was increased in patients with heart and kidney involvement, as well as in vasculitis patients, comparing to those who have no such manifestations (p=0.017, 0.046, and 0.009, respectively). We detected 58 (54.72%) anti-elastase positive RA patients, with the mean concentration 0.137 (0.103–0.171) ODU. Anti-elastase positive patients had significantly increased frequencies of anemia (p=0.025) and vasculitis (p=0.017) comparing to the negative subgroup. The prevalence of anti-elastase Ab was also increased along with RA activity. Concentrations of these two Ab were positively correlated (r=0.866, p<0.001).For anti-elastin Ab assay (cutoff point 0.112 ODU) diagnostic sensivity in RA patients was 72 (62–87)%, specificity 50 (41–64)%, AUC of ROC curve 0.703 (0.590–0.797). For anti-elastase Ab assay (cutoff point 0.115 ODU) the respective values were 77 (62–87)%, 81 (59–91)%, and 0.822 (0.675–0.923).
Conclusions Anti-elastin and, increasingly, anti-elastase antibodies are valuable candidate markers to improve diagnosis of RA and, particularly, rheumatoid vasculitis and heart involvement. Further investigations are needed to assess sensivity and specificity of these markers being included in the comprehensive diagnostic algorithms.
Gontar IP, Simakova ES, Trofimenko AS, Zborovskaya IA. An approach for removal of DNA-containing immune complexes from blood using composite sorbent. Patent RU2441674 (2010) [in Russian].
Disclosure of Interest None declared