Background/Purpose: 1) to evaluate the relationship among adipose tissue dysfunction, autoimmunity and disease activity in rheumatoid arthritis (RA) patients; 2) to analyze the direct effect of antibodies to citrullinated protein antigens (ACPAs) on the adipose tissue (AT) function and 3) to evaluate the role of insulin resistance (IR) and adipocytokines in the therapeutic response with biological treatments.

Methods: 1) Design: cross-sectional study (150 RA patients and 50 healthy donors (HDs)) and longitudinal study (122 RA patients treated with anti-TNF-a (45), anti-IL6R (22) and anti-CD20 (55) therapies after 6 months of treatment). Patients were classified in responders or non-responders based on EULAR criteria. Disease activity (DAS-28), autoimmunity, acute phase reactants (CRP and ESR) and cardiovascular disease (CVD) risk factors were evaluated. The serum levels of adipocytokines (TNF-a, IL-1b, IL-6, leptin, adiponectin, resistin, visfatin, omentin and vaspin) were measured by ELISA. Next, in vitro experiments with human AT and adipocyte and macrophage cell lines treated with G immunoglobulins isolated from HDs and RA patients were performed. The expression of genes related to inflammation, lipid accumulation and adipogenesis was analyzed in all experiments; 3) a collagen induced arthritis (CIA) mice was developed. Plasma and AT were analyzed.

Results: The levels of adipocytokines were significantly altered in RA serum and associated with disease activity. Likewise, homeostatic model assessment of insulin resistance (HOMA-IR) correlated to DAS28. On the other hand, ACPAs levels correlated with adipocytokine profile suggesting a role of ACPAs in the dysregulation of AT. AT of lean CIA mice showed higher gene expression of specific markers of B and plasmatic cells and M1 macrophages as disease activity increased. Furthermore, the in vitro treatment of human AT with ACPAs could promote the adipose tissue dysfunction promoting an inflammatory state through the M1 polarization of macrophages and the blockage of adipocyte differentiation. Next, RA patients with higher levels of HOMA-IR presented a worse response to biological treatments. Besides, levels of vaspin and visfatin were significantly increased before the treatment in the non-responders group. Although, all treatments significantly reduced disease activity after 6 months of treatment, the effect of each one was different being the anti-CD20 treatment which modified a higher number of adipocytokines.

Conclusion: 1) IR and the altered adipocytokine profile in RA patients is associated with disease activity, the presence of autoimmunity and a worse response to therapy; 2) adipose tissue in the context of RA is altered in parallel with the disease progression, characterized by an inflammatory state due to the infiltration of macrophages and B and plasmatic cells; 3) ACPAs could be at least partially the responsible of adipose tissue dysfunction inducing inflammation and IR in macrophages and promoting a defective adipocyte differentiation.

Funded by ISCIII (PI17/01316 and PI20/0079) co-funded with FEDER, and MINECO (RyC-2017-23437).

« Back to ACR Convergence 2021

ACR Meeting Abstracts - https://acrabstracts.org/abstract/impaired-adipose-tissue-function-in-rheumatoid-arthritis-association-with-autoimmunity-disease-activity-and-therapeutic-response/