title: Adipose Tissue Macrophages in Rheumatoid Arthritis: Prevalence, Disease-Related Indicators, and Associations With Cardiometabolic Risk Factors.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Columbia University College of Physicians and Surgeons, New York, New York.
authors.forename: Jon T
authors.initials: JT
authors.lastname: Giles
authors.affiliation: Columbia University College of Physicians and Surgeons, New York, New York.
authors.forename: Antony W
authors.initials: AW
authors.lastname: Ferrante
authors.affiliation: Columbia University College of Physicians and Surgeons, New York, New York.
authors.forename: Rachel
authors.initials: R
authors.lastname: Broderick
authors.affiliation: Columbia University College of Physicians and Surgeons, New York, New York.
authors.forename: Afshin
authors.initials: A
authors.lastname: Zartoshti
authors.affiliation: Columbia University College of Physicians and Surgeons, New York, New York.
authors.forename: Janine
authors.initials: J
authors.lastname: Rose
authors.affiliation: Columbia University College of Physicians and Surgeons, New York, New York.
authors.forename: Kendall
authors.initials: K
authors.lastname: Downer
authors.affiliation: Columbia University College of Physicians and Surgeons, New York, New York.
authors.forename: Hui-Zhu
authors.initials: HZ
authors.lastname: Zhang
authors.affiliation: Columbia University College of Physicians and Surgeons, New York, New York.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Winchester
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy / Q000453:epidemiology / Q000473:pathology*; D015415:Biomarkers / Q000032:analysis; D001786:Blood Glucose / Q000032:analysis; D016022:Case-Control Studies; D005260:Female; D005355:Fibrosis; D006801:Humans; D008055:Lipids / Q000097:blood; D008264:Macrophages / Q000737:chemistry / Q000187:drug effects / Q000473:pathology*; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000453:epidemiology / Q000473:pathology*; D008875:Middle Aged; D009519:New York City / Q000453:epidemiology; D010641:Phenotype; D015995:Prevalence; D012307:Risk Factors; D050151:Subcutaneous Fat / Q000737:chemistry / Q000187:drug effects / Q000473:pathology*; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D018501:Antirheumatic Agents; D015415:Biomarkers; D001786:Blood Glucose; D008055:Lipids; C067980:CD68 antigen, human; D000097382:CD68 Molecule