Abstract
Overweight/obesity influence disease burden and clinical outcome of Rheumatoid Arthritis (RA). The impact of overweight/obesity on synovial tissue (ST) inflammation is largely unknown. Here, we investigated the histological and transcriptional signature of ST obtained from RA in different disease phases (disease onset, failure to first-line conventional DMARDs and in sustained clinical and ultrasound remission) finding that overweight/obese DMARDs naive RA showed higher likelihood of follicular synovitis, higher IHC scores for sublining inflammatory cells (CD68+, CD21+ and CD20+) and higher IL-1RA plasma levels than normal weight RA. Regardless to the synovitis pattern, overweight/obese DMARDs naive RA showed a worse clinical response to “Treat-to-target” (T2T) than normal weight RA at 6 and 12 months follow-up. Conversely, MTX-IR RA did not show significant differences in synovial inflammation based on BMI category. Overweight/obese RA in stable clinical and US remission showed higher degree of residual synovitis in terms of sublining CD68+, CD20+ cells and lining and sublining CD3+ compared to normal weight RA. Finally, gene expression profile analysis revealed that ST of overweight/obese DMARDs naive RA is enriched by CCL3 and MyD88 compared to normal weight RA in sustained disease remission, the latter correlating with BMI and IHC scores for synovial CD68+ cells. These findings suggest that indeed overweight/obese RA show higher degree of synovitis at disease onset and after remission achievement that influences the response rate to T2T and should be considered within the management of patients with RA.
Highlights
There are increasing evidences that overweight and obesity are risk factors for the development of Rheumatoid Arthritis (RA) and that a high Body Mass Index (BMI) is associated with high disease activity and disability at disease onset[1,2,3], being an independent factor of worse clinical response to RA treatment[4,5,6]
Considering the autoimmune profile, there was no significant difference in terms of autoantibody positivity in the three study cohorts based on the BMI category (p = 0.52, p = 0.48 and p = 0.61 comparing autoantibody positivity based on BMI category within the naive to treatment RA, MTX-IR RA and RA in sustained remission cohorts respectively)
This study shows that overweight/obesity affects the histological features and the gene expression profile of synovial tissue (ST) of RA patients at the time of disease onset and at achievement of sustained clinical and ultrasound remission
Summary
There are increasing evidences that overweight and obesity are risk factors for the development of Rheumatoid Arthritis (RA) and that a high Body Mass Index (BMI) is associated with high disease activity and disability at disease onset[1,2,3], being an independent factor of worse clinical response to RA treatment[4,5,6]. The aims of the present study were: (i) to define the histological features of RA ST in different disease phases (disease onset or first conventional DMARD failure) in terms of CD68+, CD21+, CD3+ and CD20+ cells ST distribution based on the BMI category; (ii) to dissect if overweight/obesity status is associated with the aberrant expression of cytokines related to inflammation [i.e. Interleukin-6 (IL-6)] and bone damage [i.e. Interleukin-1 Receptor Antagonist (IL-1RA)] in naive to treatment RA; (iii) to define if BMI category, associated with ST characteristics, may influence the response rate to a treat to target strategy in naive to treatment RA and (iv) to dissect weather the BMI category may affect the histological features of residual synovitis in RA in stable clinical and ultrasound remission
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