Distinct Features Between Hla-Dr Plus And Hla-Dr-Pd-1hi Cxcr5-T Peripheral Helper Cells In Seropositive Rheumatoid Arthritis

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 (r(s) =0.50, P = 0.002), HLA-DR- Tph cells (r(s) =0.39, P = 0 .03) and Tph1 cells (r(s) =0.41, P = 0.02). Among the other 40 immune cell subsets, HLA-DR+ Th1-17 cells (r(s) =0.38, P = 0.03), activated B cells (r(s) =-0.35, P = 0.04), plasma cells (r(s) =0.43, P = 0.01) and CD14++ CD16+ monocytes (r(s) =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.