Neutrophils, neutrophil extracellular traps, and rheumatoid arthritis: An updated review for clinicians

• Published in: Reumatología clinica (Barcelona) 2023-11, Vol.19 (9), p.515-526
• Main Authors: Frade-Sosa, Beatriz, Sanmartí, Raimon
• Format: Article
• Language: English
• Subjects: Artritis reumatoide; NETosis; Neutrophil; Neutrophil extracellular trap (NET); Neutrófilo; Rheumatoid arthritis; Trampa extracelular de neutrófilo (NET)
• ISSN: 2173-5743; 2173-5743
• DOI: 10.1016/j.reumae.2023.10.002

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by the presence of autoantibodies. Research on the pathogenic mechanisms involved in systemic autoimmune diseases has largely focused on the involvement of the adaptive immune system with dysregulated responses of T and B cells. However, in recent years, there is increasing evidence of the significant role played by the innate immune system, particularly neutrophils, in these diseases, particularly in RA. Neutrophil extracellular traps (NETs) are extracellular structures composed of remodeled and concentrated chromatin with DNA, histones, and neutrophil proteins, and were first described in 2004. It has been studied that NETs may play a pathogenic role in RA and could be a source of autoantigens, increasing the immune response in the form of autoantibodies in this disease. The possible role of NETs and other markers of neutrophil activation as biomarkers of activity in RA and other immune-mediated diseases has also been studied. This article reviews the role of NETs in RA. It discusses the role of neutrophils and the latest advances in NETs, especially their involvement in autoimmune phenomena in RA. Finally, a literature review is conducted on the determination of NETs in peripheral blood and their relationship as a biomarker of RA activity, as well as their potential role in disease monitoring. La artritis reumatoide (AR) es una enfermedad autoinmune sistémica caracterizada por la presencia de autoanticuerpos. Las investigaciones sobre los mecanismos patogénicos implicados en las enfermedades autoinmunes sistémicas se centran en gran medida en la participación del sistema inmune adaptativo con las respuestas desreguladas de las células T y B. Sin embargo, en los últimos años, aumenta la evidencia del importante papel que juega del sistema inmune innato, en particular los neutrófilos, en estas enfermedades, particularmente en la AR. Las trampas extracelulares de neutrófilos (NETs) son estructuras extracelulares compuestas por cromatina remodelada y concentrada con ADN, histonas y proteínas de los neutrófilos y son un mecanismo de acción de los neutrófilos que se describió por primera vez en 2004. Se ha estudiado que pueden desempeñar un papel patogénico en la AR y podrían ser fuente de autoantígenos e incrementar la respuesta inmunológica en forma de autoanticuerpos en esta enfermedad. También se ha estudiado el posible papel de las NETS y otros marcadores de activación neutrofílica