Background Rheumatoid arthritis (RA) is one of the most common causes of chronic arthritis that results in severe joint damage and a shorter life span (1). Although the molecular mechanisms involved in pathogenesis of RA have yet to be fully elucidated, autoantibodies are proven to play a key role in this disease. Nevertheless, despite of clear interest, specific antibodies with catalytic activity, or abzymes were not investigated in patients with early RA (ERA) (2). The main goal of our study was to determine the levels of IgG nuclease activity in RA patients and to compare them with serum nuclease activity in the same patients.
Objectives We studied 51 patients with early RA (disease duration <6 months, Disease Activity Score DAS28 5.53±1.69; 39 women, 12 men; mean age 47.5±9.3 years) and 39 healthy controls from the same regional area in Belarus. All patients were fulfilled 2010 Rheumatoid Arthritis Classification Criteria (3).
Methods The samples of polyclonal IgG isolated from sera of patients and healthy persons were investigated. IgG were purified by combined method including affinity chromatography on protein A column. All necessary experiments that confirmed abzyme activity to be an essential quality of polyclonal IgG were performed. DNAse IgG and serum activity was determined by rivanol clot prevention test and agarose electrophoresis. Calf thymus DNA (Sigma) was applied as substrate for reaction. Statistical data differences for means and medians were assessed by the Student’s t-test and Mann-Whitney’s U-test, respectively. Statistical correlations were calculated by the Spearman method.
Results The levels of DNAse IgG activity in patients with ERA (Me 4.0 units (min 3.0 max 5.0)) were significantly (d<0.0001) higher than in controls (Me 0.0 units (min 0.0 max 2.0)).The levels of DNAse serum activity in patients with ERA (Me 5.0 units (min 3.0 max 5.0)) were significantly (d<0.0001) higher than in control group (Me 0.0 units (min 0.0 max 2.0)).In patients with ERA we revealed the correlation between DNAse IgG activity and HAQ results (r=0.62), DAS28 (r=0.56), ESR (r=0.57), (d<0.05) respectively.
Conclusions To the best of our knowledge, this is the first study that provides a comprehensive analysis of levels of DNAse polyclonal IgG and serum activity in patients with ERA in comparison with the healthy persons. The established interrelationships between DNAse IgG activity and clinical and laboratorymanifestations of the disease can pose regard DNAse activity as a potent diagnostic marker of early RA.
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Nevinsky GA, Buneva VN. Catalytic antibodies in healthy humans and patients with autoimmune and viral pathologies. J Cell Mol Med 2003;7:265-76.
2010 Rheumatoid Arthritis Classification Criteria. D. Aletaha et al. Arthritis Rheum 2010;62:2569-2581.
Disclosure of Interest None Declared