Background Antibodies executing catalytic activity are referred to as antibody enzymes or short “abzymes” and may have diagnostic relevance. Despite several reports on the occurrence of DNase abzymes in systemic autoimmune rheumatic diseases, conclusive data about DNase activity of antibodies in patients with spondyloarthritides (SpAs) are lacking.
Objectives DNase IgG activity was determined in 315 patients with SpAs (99 patients with PsA, 160 patients with ReA associated with Chlamydia trachomatis urogenital infections, 56 patients with AS) and 69 healthy persons as control group.
Methods Electrophoretically and immunochemically homogeneous IgGs were obtained from patients and control sera by a multi-step purification method including complete coagulation of blood samples and treatment with 0.75% ethacridine lactate solution in a ratio of 1:2 for the removal of precipitated serum components. Affinity chromatography employing protein A-Sepharose was applied. The basic method for DNase activity measurement relies upon the capacity of rivanol to form a clot with DNA, reversely proportional to nucleic acid depolymerisation on DNase action .
Results Levels of DNase IgG activity in patients with SpAs were significantly higher (p<0.001) compared to donors while DNase IgG activity in patients with PsA exceeded the levels of patients with ReA and AS. Assay performance characteristics of abzyme activity assessment were calculated for PsA differentiation from ReA and AS by receiver operating curve (ROC) analysis. Patients suffering from PsA could readily be differentiated from AS by DNase abzyme activity detection demonstrating positive likelihood ratios greater than 5.0 for DNase activity per 1mg of purified IgG or per 1 ml of serum. All patients with SpA demonstrated a positive correlation of DNase IgG activity with the number of swollen joints (r=0.65) and pain grade (r=0.59). In patients with PsA, a similar correlation between the degree of DNase IgG activity and synovitis was detected (r=0.64). In ReA patients, we found positive correlations between DNase IgG levels and disease activity index (r=0.53), C-reactive protein (CRP) levels (r=0.58), total CD2 positive T cell count (r=0.71), CD4 positive T helper count (r=0.70). Likewise, in patients with AS, multiple moderate positive correlations of DNase IgG activity were established with the stage of spondylitis (r=0.44), BASRI (r=0.67), and occipital wall distance (r=0.55; for all p < 0.001).
Conclusions DNase IgG activity appears to be elevated in patients suffering from spondyloarthritides in particular psoriatic arthritis, reactive arthritis, and ankylosing spondylitis in comparison with healthy persons, whereas the highest DNase IgG activity has been determined in patients with psoriatic arthritis. Assessment of patient sera for DNase abzyme activity might be an intriguing new serological approach for the differential diagnosis of SpA.
Gabibov AG, Gololobov GV, Makarevich OI, Schourov DV, Chernova EA, Yadav RP. DNA-hydrolyzing autoantibodies. Appl Biochem Biotechnol. 1994;47:293-302.
Acknowledgements AK and MV were supported by the Belorussian Republican Foundation and Fundamental Research (BRFFR (04-04-81017): the Belorussian State Scientific Technical Program “Treatment and Diagnostic Technologies” (01.12.2006-2008) and the Russian Foundation of Basic Research (RFBR).
Disclosure of Interest None Declared