Background Antibodies executing catalytic activity are referred to as antibody enzymes or short “abzymes” and may have diagnostic relevance. Abzymes with deoxyribonuclease (DNase) activity have been demonstrated in patients with autoimmune and infectious diseases, but conclusive data about DNase activity of antibodies in patients with spondyloarthritides (SpAs) are lacking.
Objectives The 315 patients with SpA (175 with peripheral SpA and 140 with axial SpAs) and130 healthy persons were examined.
Methods The samples of sera and polyclonal IgG isolated from patients and healthy persons were investigated. IgG were purified from the sera by combined method of affinity chromatography on protein A column. The methods for DNAse activity assessment relied upon rivanol capacity to form a clot with DNA reversely proportional to this acid depolymerisation on the action of DNAse. The abzyme activity was then measured semiquantitatively using arbitrary units (AU) corresponding to a 6-grade visual scale (from 0 to 5 points).
Results Levels of DNase IgG activity in patients with SpAs were significantly higher (p<0,001) compared to healthy donors while DNase IgG activity in patients with peripheral SpAs exceeded (p<0,001) the levels of patients with axial SpAs. Assay performance characteristics of abzyme activity assessment were calculated for peripheral SpAs differentiation from axial SpAs by receiver operating curve (ROC) analysis. Patients with peripheral SpAs could readily be differentiated from axial SpAs 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 and pain grade. In peripheral SpAs, we found positive correlations between DNase IgG levels and disease activity index, C-reactive protein (CRP) levels, total CD2 positive T cell count, CD4 positive T helper count, and serum soluble immune complex levels. Likewise, in axial SpAs, multiple moderate positive correlations of DNase IgG activity were established with the stage of spondylitis, BASRI. The multiple relationships between DNA hydrolyzing IgG activity and clinical signs of SpAs confirmed a putative clinical significance of DNase abzymes in these clinical entities.
Conclusions Remarkably, levels of IgG DNase activity were significantly higher in sera of SpA patients than in control subjects. In patients with peripheral and axial SpAs a positive correlation of DNase IgG activity with synovitis, disease activity, and stage of spondylitis was observed, respectively. Given the involvement of autoimmune reactions in cytolysis and connective tissue degradation in peripheral SpAs, and to a lesser extent in axial SpAs, abzymes might have an impact on the pathophysiology of SpAs. Detection of IgG DNase activity in patients suffering from SpA represents an exciting new research field and may assist in the differential diagnosis of SpA.
Disclosure of Interest None declared