Distinct features between HLA-DR+ and HLA-DR- PD-1hi CXCR5- T peripheral helper cells in seropositive rheumatoid arthritis

Rheumatology (Oxford). 2021 Jan 5;60(1):451-460. doi: 10.1093/rheumatology/keaa417.


Objectives: PD-1hi CXCR5- T peripheral helper (Tph) cells are newly identified pathogenic CD4 helper T cells in RA. We evaluated the usefulness of Tph cell subsets as biomarkers of RA.

Methods: RA patients who visited our rheumatology department between May 2015 and September 2017 and met the 2010 ACR/EULAR classification criteria were included. We compared the correlation of DAS28-ESR between Tph cell subsets and 40 immune cell subsets. We also explored which subsets reflected the chronological changes in the disease activity after treatment.

Results: Thirty-four seropositive RA patients, 11 seronegative RA patients and 34 healthy controls were included. Tph cell subsets that correlated with the DAS28-ESR were HLA-DR+ Tph cells (rs = 0.50, P = 0.002), HLA-DR- Tph cells (rs = 0.39, P = 0.03) and Tph1 cells (rs = 0.41, P = 0.02). Among the other 40 immune cell subsets, HLA-DR+ Th1-17 cells (rs = 0.38, P = 0.03), activated B cells (rs = -0.35, P = 0.04), plasma cells (rs = 0.43, P = 0.01) and CD14++ CD16+ monocytes (rs = 0.36, P = 0.04) correlated, but not strongly as HLA-DR+ Tph cells. However, MTX treatment reduced the proportion of HLA-DR+ Tph cells independently of the disease activity. In contrast, HLA-DR- Tph cells accurately reflected the change in the DAS28-ESR during MTX treatment.

Conclusion: HLA-DR+ Tph cells were decreased with MTX treatment, independent of the disease activity, while HLA-DR- Tph cells reflected the disease activity accurately during the treatment.

Keywords: HLA-DR; T peripheral helper cells; biomarker; rheumatoid arthritis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / drug therapy
  • Arthritis, Rheumatoid / immunology*
  • Arthritis, Rheumatoid / metabolism
  • Female
  • HLA-DR Antigens / metabolism*
  • Humans
  • Male
  • Methotrexate / therapeutic use*
  • Middle Aged
  • T-Lymphocytes, Helper-Inducer / immunology*
  • T-Lymphocytes, Helper-Inducer / metabolism


  • Antirheumatic Agents
  • HLA-DR Antigens
  • Methotrexate