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Ambiguities in Neutrophil Extracellular Traps. Ongoing Concepts and Potential Biomarkers for Rheumatoid Arthritis: A Narrative Review


Andrei S. Trofimenko*, Elena E. Mozgovaya, Svetlana A. Bedina and Alexander A. Spasov  


Objective: Consolidation of current research findings as well as most important concepts regarding neutrophil extracellular traps (NETs) in rheumatoid arthritis.

Data sources: Relevant publications released from 2004 to 2018 were identified using PubMed, Web of Science, Scopus, and eLibrary databases. Primary search terms used were “neutrophil extracellular traps” or “NETs” in combination with “rheumatoid arthritis”.

Data synthesis: NETs are distinctive structures promoting capture and non-phagocytic cleavage of foreign substances. NETs usually consist of a thin chromatin fibers decorated with various molecules of granular, cytosolic, and cytoskeletal origin. NETosis could develop in two ways: either with neutrophil death or when viability of the cell prolongs. ROS generation and pronounced protein citrullination are essential during initial phase of NETs formation. NETosis is considered to have certain immunological consequences, including DAMPs-mediated signalling, proinflammatory cytokine secretion, and contact of extensively modified self and foreign epitopes with antigen presenting cells. There are several putative pathogenetic links between NETosis, citrullination, neoepitope formation, and production of anticitrulline autoantibodies that can strongly influence on rheumatoid arthritis progression. NET-induced vascular injury in rheumatoid arthritis could arise both directly from NETs and indirectly through enhanced thrombosis and atherosclerosis.

Conclusion: NETs are currently estimated as a possible influential factor of rheumatoid arthritis initiation and/or progression, especially in the context of vascular involvement. NETs can also serve as a source of novel antigenic biomarkers for diagnosis of rheumatoid arthritis.


Neutrophil Extracellular Traps, Netosis, Polymorhonuclear Cells, Rheumatoid Arthritis, Immunology, Autoimmunity, Anti-Citrulline Antibodies


Research Institute for Clinical and Experimental Rheumatology, Volgograd, Research Institute for Clinical and Experimental Rheumatology, Volgograd, Research Institute for Clinical and Experimental Rheumatology, Volgograd, Volgograd State Medical University, Volgograd

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