Differences in synovial tissue infiltrates between anti-cyclic citrullinated peptide-positive rheumatoid arthritis and anti-cyclic citrullinated peptide-negative rheumatoid arthritis

Arthritis Rheum. 2008 Jan;58(1):53-60. doi: 10.1002/art.23148.


Objective: To compare synovial tissue infiltrates from patients with anti-cyclic citrullinated peptide (anti-CCP)-positive rheumatoid arthritis (RA) with those from patients with anti-CCP-negative RA.

Methods: Synovial tissue samples were obtained arthroscopically from the inflamed knee joints of 57 patients with RA (34 of whom were anti-CCP positive) and examined for several histologic features along with immunohistologic expression of cell markers. Joint damage was assessed using the Kellgren/Lawrence (K/L) scale (range 0-4) on standard anteroposterior radiographs. In 31 patients (18 of whom were anti-CCP positive), synovial tissue was available from an earlier time point, allowing analysis of temporal changes.

Results: Synovial tissue from anti-CCP-positive patients was characterized by a higher mean number of infiltrating lymphocytes (61.6 versus 31.4/high-power field [hpf] [400x]; P=0.01), less extensive fibrosis (mean score of 1.2 versus 2.0; P=0.04), and a thinner synovial lining layer (mean score of 2.1 versus 3.3; P=0.002) compared with synovial tissue from anti-CCP-negative patients. Anti-CCP-positive patients expressed more CD3, CD8, CD45RO, and CXCL12. More anti-CCP-positive patients had a K/L score >1 compared with anti-CCP-negative patients. The difference in the mean lymphocyte counts was already present a mean of 3.8 years before the index biopsy (76.7 lymphocytes/hpf and 26.7 lymphocytes/hpf in anti-CCP-positive patients and anti-CCP-negative patients, respectively; P=0.008) and was independent of disease duration and K/L score.

Conclusion: Synovitis in patients with anti-CCP-positive RA differs from that in patients with anti-CCP- negative RA, notably with respect to infiltrating lymphocytes, and is associated with a higher rate of local joint destruction.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Arthritis, Rheumatoid / immunology
  • Arthritis, Rheumatoid / metabolism*
  • Arthritis, Rheumatoid / pathology*
  • Female
  • Fibrosis
  • Humans
  • Immunohistochemistry
  • Lymphocytes / pathology
  • Male
  • Middle Aged
  • Osteoarthritis / immunology
  • Osteoarthritis / metabolism
  • Osteoarthritis / pathology
  • Peptides, Cyclic / immunology
  • Peptides, Cyclic / metabolism*
  • Synovial Membrane / immunology
  • Synovial Membrane / metabolism
  • Synovial Membrane / pathology
  • Synovitis / immunology
  • Synovitis / metabolism*
  • Synovitis / pathology*


  • Peptides, Cyclic
  • cyclic citrullinated peptide