Apoptosis and secondary necrosis of neutrophils and monocytes in the immunopathogenesis of rheumatoid arthritis: a cohort study

Rheumatoid arthritis (RA) is a progressive chronic inflammatory and autoimmune joint disease. Neutrophils and monocytes are the main target cells of innate immune defense that modulate the course of inflammatory rheumatic diseases. Dysfunctional phagocytosis is a common feature in RA. The aim of this study was to evaluate the diagnostic value of apoptotic changes in neutrophils and monocytes and their relationship with rheumatoid activity measured by the DAS28 score. We used the APOLECT flow cytometric assay for evaluating primary necrotic, apoptotic, and secondary necrotic neutrophils and monocytes determination in RA patients compared with healthy controls. The apoptotic granulocytes were greater in RA patients compared to healthy controls (0.76 +/- 0.15% vs. 0.58 +/- 0.17%,P < 0.05). The percentage of primary necrotic granulocytes was significantly elevated in RA patients compared to healthy controls (3.84 +/- 0.5% vs. 1.96 +/- 0.33%). No significant difference was noted for primary necrotic monocytes. The number of secondary necrotic granulocytes and monocytes was high in RA patients (0.94 +/- 0.15% vs. 0.4 +/- 0.06% and 4.83 +/- 1.06% vs. 1.8 +/- 0.33%, respectively). The obtained results suggest that neutrophils and monocytes undergo apoptotic modifications which are accompanied by secondary necrotic cells formation in RA. These shifts may lead to autoantigen accumulation that results in the progressive course RA.