Background/Purpose:

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 characterized 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). Therefore, our objective was 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-naïve early RA patients (eRA) (2010 ACR criteria) with a disease duration <24 weeks (n=42), and healthy controls (HC) matched for age and gender (n=42). For comparison, blood was also drawn from 66patients with established RA (disease duration > 2 years), 45 patients with Spondyloarthritis (SpA), and their age and gender-matchedHC (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 naïve for biological agents. SpA patients were receiving NSAIDs, low-dose oral methotrexate and/or sulphasalazine and were naïve 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<2.6, n=23) were not different from HC. Furthermore, Tph cells were present in the synovial fluid of seropositive RA (n= 4) but not of seronegative RA (n= 3) or SpA (n=3).

Conclusion:

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.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/increased-frequency-of-circulating-cd4cxcr5-pd1hi-peripheral-helper-t-ctph-cells-in-patients-with-seropositive-early-rheumatoid-arthritis-ra/