Background Early diagnosis and treatment of rheumatoid arthritis (RA) is of paramount importance for achieving a better disease outcome. Seropositive arthralgia patients (SAP), positive for anti citrullinated protein antibody (ACPA) and/or rheumatoid factor (RF) with (a history of) arthralgia, have a “high risk” of developing RA. Therefore it is necessary to understand which preclinical immunological factors play a role in the progression towards RA in SAP since this could help identify individuals earlier and result in early intervention.
Objectives This prospective study aimed at identifying whether altered regulatory T-cells (Tregs) levels and subsets, besides a broadened ACPA response, are biomarkers for RA development in SAP.
Methods Thirty-four consecutive SAP were prospectively assessed every 6 months for at least 2 years. Every visit, peripheral blood mononuclear cells (PBMCs) were isolated and stored. At inclusion, peripheral Treg (CD4+CD25+FoxP3+) levels and Treg subsets, defined as CD45RA+FoxP3low naive Treg cells (Fr I), CD45RA–FoxP3high activated Treg cells (Fr II) and cytokine producing CD45RA–FoxP3low non-Treg cells (Fr III), were compared to age and sex matched healthy controls (HC, n=16) and treatment naive RA patients (n=12). SAP that developed RA during follow-up were compared to non-switchers on Treg levels and functional Treg subsets. To assess broadening of the IgG and IgA ACPA repertoire in serum, reactivity was measured against citrullinated peptides from fibrinogen, α-enolase and vimentin.
Results Total Treg levels were similar between HC, SAP and RA patients. Although functional Treg subsets Fr I and Fr II were comparable between groups, Fr III was increased in SAP compared to HC (p=0.01). Fourteen (41%) SAP developed RA during follow-up. Their Treg levels were comparable to those of non-switched SAP. At RA diagnosis, Treg levels in switched SAP were not changed compared to 6 months before. Switched SAP displayed an extended IgG ACPA repertoire compared to non-switched SAP (p=0.046).
Conclusions Total and functional Treg levels do not indicate development of RA in SAP, in contrast to an extended IgG and IgA ACPA repertoire. Hence, there is presumably no contribution of altered Treg levels leading to the loss in suppression of autoimmunity in RA pathology.
Disclosure of Interest None declared