
At RA diagnosis, Treg numbers in switched SAP were similar to 6 months before. Their Treg numbers and subsets were comparable to non-switched SAP. Fourteen (41%) SAP developed RA during follow-up.

Although the bonafide Treg subsets Fr I and Fr II were comparable between groups, Fr III was increased in SAP compared to HC (p = 0.01). Treg numbers were similar between HC, SAP and RA patients. To assess the ACPA repertoire, IgG and IgA reactivity was measured against citrullinated peptides from fibrinogen, α-enolase and vimentin. Also, Treg numbers and subsets were compared in switched SAP before and at diagnosis. SAP that developed RA were compared to non-switchers and analyzed for Treg numbers and Treg subsets at inclusion.

At inclusion, peripheral Treg (CD4+CD25+FoxP3+) numbers and subsets, defined as CD45RA+FoxP3low naive Tregs (Fr I), CD45RA-FoxP3high activated Tregs (Fr II) and CD45RA-FoxP3low non-Tregs (Fr III), were compared to age- and sex-matched healthy controls (HC, n = 16) and treatment-naive RA patients (n = 12).

Thirty-four consecutive SAP were prospectively assessed every 6 months for minimally 2 years. This prospective study aimed to determine whether altered peripheral regulatory T-cells (Tregs) and defined subsets, besides a broadened anti-citrullinated protein antibody (ACPA) response, may qualify as biomarkers for RA development in SAP. Seropositive arthralgia patients (SAP) are at high risk of developing rheumatoid arthritis (RA).
