Clinical and Experimental Medicine

, Volume 18, Issue 4, pp 487–494 | Cite as

Clinicopathological value of programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) expression in synovium of patients with rheumatoid arthritis

  • Kotaro Matsuda
  • Hiroaki MiyoshiEmail author
  • Koji Hiraoka
  • Tetsuya Hamada
  • Shiro Yoshida
  • Yukinao Ishibashi
  • Toshiaki Haraguchi
  • Naoto Shiba
  • Koichi Ohshima
Original Article


The etiology of rheumatoid arthritis (RA) is thought to involve dysfunction of the programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) pathway; PD-1 negatively regulates autoimmunity by interacting with its ligand, PD-L1. We therefore investigated PD-1/PD-L1 expression in synovial tissue of patients with RA. We immunohistochemically stained synovial specimens from 51 patients with RA and assessed the association between PD-1/PD-L1 expression and rheumatoid factor (RF), the total count of infiltrating T cells, C-reactive protein (CRP), and Krenn’s synovitis score. PD-1 expression on infiltrating lymphocytes was detected in 34/51 RA cases (66.7%), while PD-1 expression was very mildly correlated only with the number of total infiltrating T cells (R2 = 0.1011, P = 0.0230). On the other hand, PD-L1 expression on synovial lining cells was observed in 37/51 RA cases (72.5%). Furthermore, a higher PD-L1 expression was significantly associated with RF positive state (P = 0.0454), and the correlations between PD-L1 expression and the number of infiltrating T cells (R2 = 0.5571, P < 0.0001), CRP (R2 = 0.4060, P < 0.0001), and Krenn’s synovitis score (R2 = 0.7785, P < 0.0001) were confirmed. PD-1 was expressed on infiltrating lymphocytes, while PD-L1 was expressed on synovial lining cells; the expression of PD-L1 on synovial lining cells was significantly correlated with the active state of the disease. These data suggest that PD-1/PD-L1 pathway may have an important role in the pathogenesis of RA.


Programmed cell death 1 (PD-1) Programmed cell death ligand 1 (PD-L1) Rheumatoid arthritis (RA) Immunohistochemistry Synovium 



We offer our special thanks to Mayumi Miura, Kanoko Miyazaki, Yuki Morotomi, Chie Kuroki, Kaoruko Nagatomo, Kensaku Sato, and Kazutaka Nakashima for their technical support. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of PathologyKurume University School of MedicineKurumeJapan
  2. 2.Department of Orthopedic SurgeryKurume University School of MedicineKurumeJapan

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