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

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, CD45110, 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.