Pathogenic mechanisms involving the interplay between adipose tissue and auto-antibodies in rheumatoid arthritis

Iván Arias-de la Rosa; Alejandro Escudero-Contreras; Miriam Ruiz-Ponce; Laura Cuesta-López; Cristóbal Román-Rodríguez; Carlos Pérez-Sánchez; Patricia Ruiz-Limón; Rocío Guzman- Ruiz; Fernando Leiva-Cepas; Juan Alcaide; Pedro Segui; Chamaida Plasencia; Ana Martinez-Feito; Pilar Font; María C Ábalos; Rafaela Ortega; María M Malagón; Francisco J Tinahones; Eduardo Collantes-Estévez; Chary López-Pedrera; Nuria Barbarroja

doi:10.1016/j.isci.2022.104893

Pathogenic mechanisms involving the interplay between adipose tissue and auto-antibodies in rheumatoid arthritis

iScience. 2022 Aug 6;25(9):104893. doi: 10.1016/j.isci.2022.104893. eCollection 2022 Sep 16.

Authors

Iván Arias-de la Rosa¹, Alejandro Escudero-Contreras², Miriam Ruiz-Ponce², Laura Cuesta-López², Cristóbal Román-Rodríguez², Carlos Pérez-Sánchez², Patricia Ruiz-Limón^{3

4}, Rocío Guzman- Ruiz^{5

4}, Fernando Leiva-Cepas⁶, Juan Alcaide^{3

4}, Pedro Segui⁷, Chamaida Plasencia⁸, Ana Martinez-Feito⁹, Pilar Font², María C Ábalos², Rafaela Ortega², María M Malagón^{5

4}, Francisco J Tinahones^{3

4}, Eduardo Collantes-Estévez², Chary López-Pedrera², Nuria Barbarroja²

Affiliations

¹ GENYO (Centre for Genomics and Oncological Research: Pfizer, University of Granada, Andalusian Regional Government, PTS Granada, Granada, Spain.
² Rheumatology Service/Department of Medical and Surgical Sciences, Maimonides Institute for Biomedicine Research of Cordoba (IMIBIC)/ /University of Cordoba/ Reina Sofia University Hospital, Córdoba, Spain.
³ Department of Endocrinology and Nutrition, Virgen de la Victoria Hospital, Instituto de Investigación Biomédica de Málaga (IBIMA), Málaga University, Málaga, Spain.
⁴ CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain.
⁵ Department of Cell Biology, Physiology, and Immunology, Maimonides Institute for Biomedical Research of Cordoba (IMIBIC)/University of Córdoba/Reina Sofía University Hospital, Córdoba, Spain.
⁶ Department of Pathology, Reina Sofia University Hospital, Cordoba, Spain.
⁷ Radiology Service, Maimonides Institute for Biomedical Research of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Córdoba, Cordoba, Spain.
⁸ Rheumatology Department, La Paz University Hospital, Madrid, Spain.
⁹ Immunorheumatology Department, IDIPAZ, Madrid, Spain.

Abstract

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.

Keywords: Health sciences; Immunology; Rheumatology.