Monocyte Extracellular Traps: Generation Patterns Depending on the Autoimmune Inflammation Stage in Rheumatoid Arthritis

Objective: Recent studies have demonstrated that neutrophiles and extracellular traps (NETs) generated by them participate in the initiation and progression of autoimmune inflammation in rheumatoid arthritis (RA) patients. At the same time, the key role in the immune response as a result of impaired antigen processing and presentation belongs to macrophages/monocytes, which are the main antigen-presenting cells. Thus, the study of the role of monocytes and their extracellular traps (METs) in RA pathogenesis is promising and of particular interest. The purpose of this work is to study the main features of extracellular traps formed by circulating monocytes in RA patients depending on the autoimmune inflammation stage. Materials and methods: The study included 37 RA patients and 35 healthy individuals. Circulating monocytes were isolated by single-stage centrifugation in an iogexol gradient with a density of 1068 kg/m3. Cells were identified by histochemistry, their activation was assessed using a nitroblue tetrazolium assay. MET formation was stimulated by a phorbol-12-myristate-13-acetate (PMA) solution and visualized by fluorescence microscopy with SYBR green. Results and discussion: In patients with inactive RA, the number of monocytes generating both spontaneous and PMA-induced METs was higher compared to the reference group. Transformation of autoimmune inflammation in RA from remission to the active phase was accompanied by a further increase in the proportion of monocytes generating METs spontaneously and in the presence of PMA (by 114 and 44.2% compared to the reference group, respectively). RA activation is evidenced by an increase in the number of monocytes spontaneously generating METs by more than 17.8%. Conclusions: The obtained data allows to assume the possible participation of METs in the initiation and maintenance of autoimmune inflammation in RA along with NETs, which are the source of citrullinated neoepitopes. Because of this, METs can be considered as a new biomarker in the diagnosis of RA.