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Adipose Tissue Macrophages in Rheumatoid Arthritis: Prevalence, Disease‐Related Indicators, and Associations With Cardiometabolic Risk Factors
Author(s) -
Giles Jon T.,
Ferrante Antony W.,
Broderick Rachel,
Zartoshti Afshin,
Rose Janine,
Downer Kendall,
Zhang HuiZhu,
Winchester Robert J.
Publication year - 2018
Publication title -
arthritis care and research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.032
H-Index - 163
eISSN - 2151-4658
pISSN - 2151-464X
DOI - 10.1002/acr.23253
Subject(s) - medicine , rheumatoid arthritis , adipose tissue , insulin resistance , c reactive protein , inflammation , fibrosis , tumor necrosis factor alpha , body mass index , endocrinology , immunology , obesity
Objective Adipose tissue macrophages (ATMs) are a potent source of inflammatory cytokines, with profound effects on adipose tissue function, yet their potential role in rheumatoid arthritis (RA) pathobiology is largely unstudied. Methods Periumbilical subcutaneous adipose tissue was obtained from 36 RA patients and 22 non‐RA controls frequency matched on demographics and body mass index. Samples were stained for the macrophage marker CD68, and the average proportions of ATMs, crown‐like structures (periadipocyte aggregates of 3 or more ATMs), and fibrosis were compared between groups. Results The adjusted proportion of ATMs among all nucleated cells was 76% higher in RA than in non‐RA samples (37.7 versus 21.3%, respectively; P < 0.001), and the adjusted average number of crown‐like structures was more than 1.5‐fold higher in the RA group than in controls (0.58 versus 0.23 crown‐like structure/high‐power field, respectively; P = 0.001). ATMs were significantly more abundant in early RA and in those with anti–cyclic citrullinated peptide seropositivity. Users of methotrexate, leflunomide, and tumor necrosis factor inhibitors had a significantly lower proportion of ATMs compared with nonusers. Crown‐like structures were significantly higher in patients with rheumatoid factor seropositivity and in those with C‐reactive protein levels ≥10 mg/liter, and significantly lower among those treated with statins. Linear ATMs were significantly associated with whole‐body insulin resistance, but not with serum lipids. Conclusions ATMs and crown‐like structures were more abundant in RA patients and were associated with systemic inflammation, autoimmunity, and whole‐body insulin resistance, suggesting possible contributions to the RA disease process. Lower levels of ATMs and crown‐like structures associated with specific RA treatments suggest that adipose tissue inflammation may be ameliorated by immunomodulation.