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Pathogenic mechanisms involving the interplay between adipose tissue and auto-antibodies in rheumatoid arthritis. 2022
Iván Arias-de la Rosa, and
Alejandro Escudero-Contreras, and
Miriam Ruiz-Ponce, and
Laura Cuesta-López, and
Cristóbal Román-Rodríguez, and
Carlos Pérez-Sánchez, and
Patricia Ruiz-Limón, and
Rocío Guzman- Ruiz, and
Fernando Leiva-Cepas, and
Juan Alcaide, and
Pedro Segui, and
Chamaida Plasencia, and
Ana Martinez-Feito, and
Pilar Font, and
María C Ábalos, and
Rafaela Ortega, and
María M Malagón, and
Francisco J Tinahones, and
Eduardo Collantes-Estévez, and
Chary López-Pedrera, and
Nuria Barbarroja
GENYO (Centre for Genomics and Oncological Research: Pfizer, University of Granada, Andalusian Regional Government, PTS Granada, Granada, Spain.
We aimed to evaluate the association between adipose tissue (AT) dysfunction, autoimmunity, and disease activity in rheumatoid arthritis (RA). A cross-sectional study including 150 RA patients and 50 healthy donors and longitudinal study with 122 RA patients treated with anti-tumor necrosis factor (TNF)-α, anti-interleukin 6 receptor (IL6R) or anti-CD20 therapies for 6 months were carried out. In vitro experiments with human AT and adipocyte and macrophage cell lines were performed. A collagen-induced arthritis mouse model was developed. The insulin resistance and the altered adipocytokine profile were associated with disease activity, the presence of anti-citrullinated proteins anti-bodies (ACPAs), and worse response to therapy in RA. AT in the context of arthritis is characterized by an inflammatory state alongside the infiltration of macrophages and B/plasmatic cells, where ACPAs can have a direct impact, inducing inflammation and insulin resistance in macrophages and promoting a defective adipocyte differentiation, partially restored by biologicals.
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