Objective: Podoplanin (PDPN) mediates tumor cell migration and invasion, which phenomena
might also play a role in severe rheumatoid arthritis (RA). Therefore, the precise cellular
distribution of PDPN and it’s relationships with inflammation was studied in RA treated with biologic
disease-modifying anti-rheumatic drugs (DMARD) or conventional DMARDs (cDMARD).
Methods: PDPN+ cells were immunostained by NZ-1 mAb, and scored (3+; >50%/ area, 2+; 20%-
50%, 1+; 5%-20%, 0: <5%) in synovial tissues from RA treated with biologic DMARDs (BIO,
n=20) or cDMARD (n=20) for comparison with osteoarthritis (OA, n=5), followed by cell grading of
inflammation and cell-typing.
Results: Inflammatory synovitis score was 1.4 in both BIO and cDMARD, compared to only 0.2 in
OA. PDPN+ cells were found in the lining layer (BIO 1.6, cDMARD 1.3, OA 0.2) and lymphoid
aggregates (BIO 0.6, cDMRD 0.7, OA 0.2), and correlated with RA-inflammation in BIO- and
cDMARD-groups in both area (r=0.7/0.9, r=0.6/0.7, respectively p<0.05). PDPN was expressed in
CD68+ type A macrophage-like and 5B5+ type B fibroblast-like cells in the lining layer, and in IL-
17+ cells in lymphoid aggregates in RA.
Conclusion: PDPN was markedly increased in the immunologically inflamed RA synovitis, which
was surgically treated due to BIO- and cDMARD-resistant RA. PDPN may have potential of a new
marker of residual arthritis in local joints for inflammation-associated severe RA.