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, 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.


CONCLUSIONS
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.
van Oosterhout
M
M
Leiden University Medical Center, Leiden, The Netherlands. m.van_oosterhout@lumc.nl
Bajema
I
I
Levarht
E W N
EW
Toes
R E M
RE
Huizinga
T W J
TW
van Laar
J M
JM
D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D005355:Fibrosis; D006801:Humans; D007150:Immunohistochemistry; D008214:Lymphocytes / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D010456:Peptides, Cyclic / Q000276:immunology / Q000378:metabolism*; D013583:Synovial Membrane / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D013585:Synovitis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*
D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide