AbstractObjectiveTo 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.MethodsSynovial 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.ResultsSynovial 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] [400×]; 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.ConclusionSynovitis 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.