Clinical Rheumatology

, Volume 32, Issue 6, pp 853–861

Inflammatory immune cell responses and Toll-like receptor expression in synovial tissues in rheumatoid arthritis patients treated with biologics or DMARDs

  • Yuya Takakubo
  • Yasunobu Tamaki
  • Tomoyuki Hirayama
  • Kiyoshi Iwazaki
  • Kan Sasaki
  • Akiko Sasaki
  • Hiroharu Ohki
  • Noe Takakubo
  • Yrjö T. Konttinen
  • Michiaki Takagi
Original Article

DOI: 10.1007/s10067-013-2209-3

Cite this article as:
Takakubo, Y., Tamaki, Y., Hirayama, T. et al. Clin Rheumatol (2013) 32: 853. doi:10.1007/s10067-013-2209-3

Abstract

Biologic antirheumatic drugs (BIO) have been reported to be potent therapeutic agents in the prevention of inflammatory joint destruction in rheumatoid arthritis (RA). The aim of this study was to investigate the immune-inflammatory cells, including Toll-like receptor (TLR)-equipped cells, in synovial tissue samples from RA patients on BIO compared to patients, who are only on conventional disease-modifying antirheumatic drug (DMARD). We analyzed immune-inflammatory cells in RA synovitis in patients of BIO group (n = 20) or DMARD group (n = 20). The grading scores of synovitis was 1.7 and 1.8 in each BIO and DMARD group and correlated best with the CD3+ T (r = 0.71/0.70, p < 0.05) and CD20+ B (r = 0.80/0.84, p < 0.05) cells in the both groups, but less well with the CD68+ macrophages and S-100+ dendritic cells (DCs). Interestingly, both T (116 vs. 242, p < 0.05) and B (80 vs. 142, p < 0.05) cell counts were lower in the BIO than in the DMARD group, whereas macrophage and DC counts did not differ. In contrast, the C-reactive protein (CRP) and disease activity score DAS28-CRP did not show clear-cut correlations with the inflammatory grade of the synovitis (r range, 0–0.35). Similar numbers of cells immunoreactive for TLR-1 to TLR-6 and TLR-9 were found in synovitis in both groups. Patients clinically responding to biologics might still have the potential of moderate/severe local joint inflammation, composed in particular of and possibly driven by the autoinflammatory TLR+ cells.

Keywords

Antirheumatic agents Cellular immune response Rheumatoid arthritis Synovial membrane Toll-like receptors 

Copyright information

© Clinical Rheumatology 2013

Authors and Affiliations

  • Yuya Takakubo
    • 1
    • 2
  • Yasunobu Tamaki
    • 1
  • Tomoyuki Hirayama
    • 1
  • Kiyoshi Iwazaki
    • 1
  • Kan Sasaki
    • 1
  • Akiko Sasaki
    • 1
  • Hiroharu Ohki
    • 1
  • Noe Takakubo
    • 2
    • 3
  • Yrjö T. Konttinen
    • 2
    • 4
    • 5
    • 6
  • Michiaki Takagi
    • 1
  1. 1.Department of Orthopedic SurgeryYamagata University School of MedicineYamagataJapan
  2. 2.Department of Medicine, Biomedicum HelsinkiUniversity of HelsinkiHelsinkiFinland
  3. 3.Department of Clinical MedicineYamagata Saisei HospitalYamagataJapan
  4. 4.Department of Medicine/Invärtes medicinHelsinki University Central HospitalHelsinkiFinland
  5. 5.ORTON Orthopedic Hospital of the ORTON FoundationHelsinkiFinland
  6. 6.COXA Hospital for Joint ReplacementTampereFinland

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