Increased Frequency Of Circulating Cd4+Cxcr5-Pd1hi Peripheral Helper T (Ctph) Cells In Patients With Seropositive Early Rheumatoid Arthritis (Ra)

Background A novel population of CD4 +T cells with B cell helping capacity has been described in the synovial tissues and peripheral blood of seropositive RA patients with an established disease, and termed ‘peripheral helper’ (Tph) cells. (Rao DA et al, Nature 2017) Tph cells are characterised by the lack of CXCR5 together with a bright expression of PD-1 (CD4 +CXCR5-PD-1hi T cells). As opposed to CD4 +CXCR5+PD-1hi follicular helper T cells (Tfh), Tph cells are not located in lymphoid organs but accumulate in inflamed tissues. Tph cell numbers have not been previously examined in early RA (eRA). Objectives To study the frequency of circulating CD3 +CD4+CXCR5-PD-1hi Tph cells (cTph), in patients with eRA. Methods Peripheral blood was drawn from DMARD-naive early RA patients (eRA) (2010 ACR criteria) with a disease duration 2 years), 45 patients with Spondyloarthritis (SpA), and their age and gender-matched HC (one HC per patient). In addition, synovial fluid from 7 patients with established RA and 3 patients with SpA was examined. Established RA patients were receiving low-dose oral methotrexate and were naive for biological agents. SpA patients were receiving NSAIDs, low-dose oral methotrexate and/or sulphasalazine and were naive for biologicals. After isolation by Ficoll-Hypaque gradient, PBMCs were stained with antibodies to CD3, CD4, CXCR5, ICOS and PD-1, and examined by flow cytometry. Results The frequency of circulating CXCR5- cells gated for CD4 +T cells was not different among the studied groups. In contrast, eRA patients demonstrated an increased frequency of circulating CD4 +CXCR5-PD-1hi Tph and CD4 +CXCR5-PD-1hiICOS+ T cells. When examining seropositive (RF +and/or ACPA+, n=25) and seronegative eRA patients (RF- and ACPA-, n=17) separately, it was evident that the above described alterations were only apparent in seropositive eRA. Likewise, increased cTph numbers were observed in seropositive (n=47) but not seronegative (n=19) established RA, and not in SpA patients (n=45), which is consistent with data reported by Rao et al. Interestingly, this increased cTph cell frequency was observed only in seropositive RA patients with an active disease (DAS28 >2.6, n=24), whereas the numbers of cTph cells in established RA patients who had achieved remission (DAS28 Conclusions Tph cells may play an important role in the pathogenesis of seropositive but not seronegative RA. An increased cTph cell frequency is a marker of active, seropositive RA. Reference [1] Rao DA, et al. Nature2017;542(7639):110–114. Disclosure of Interest None declared