Regulatory CD4+T-Cell Subsets and Anti-Citrullinated Protein Antibody Repertoire: Potential Biomarkers for Arthritis Development in Seropositive Arthralgia Patients?

Koen M. J. Janssen, Johanna Westra, Paulina Chalan, Annemieke M. H. Boots, Menke J. de Smit, Arie Jan van Winkelhoff, Arjan Vissink, Elisabeth Brouwer*

*Bijbehorende auteur voor dit werk

Onderzoeksoutput: ArticleAcademicpeer review

15 Citaten (Scopus)
253 Downloads (Pure)

Samenvatting

Objective

Seropositive arthralgia patients (SAP) are at high risk of developing rheumatoid arthritis (RA). 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.

Methods

Thirty-four consecutive SAP were prospectively assessed every 6 months for minimally 2 years. At inclusion, peripheral Treg (CD4(+)CD25(+)FoxP3(+)) numbers and subsets, defined as CD45RA(+)FoxP3(low) naive Tregs (Fr I), CD45RA(-)FoxP3(high) activated Tregs (Fr II) and CD45RA(-)FoxP3(low) non-Tregs (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 were compared to non-switchers and analyzed for Treg numbers and Treg subsets at inclusion. Also, Treg numbers and subsets were compared in switched SAP before and at diagnosis. To assess the ACPA repertoire, IgG and IgA reactivity was measured against citrullinated peptides from fibrinogen, alpha-enolase and vimentin.

Results

Treg numbers were similar between HC, SAP and RA patients. 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). Fourteen (41%) SAP developed RA during follow-up. Their Treg numbers and subsets were comparable to non-switched SAP. At RA diagnosis, Treg numbers in switched SAP were similar to 6 months before. Switched SAP displayed a more diverse IgG ACPA repertoire compared to non-switched SAP (p = 0.046) and showed more IgA reactivity than non-switched SAP reaching significance for Fib1 only (p = 0.047).

Conclusion

Numbers of Total Treg and bonafide Treg subsets are not indicative for RA development in SAP, opposed to the ACPA repertoire.

Originele taal-2English
Artikelnummere0162101
Aantal pagina's13
TijdschriftPLoS ONE
Volume11
Nummer van het tijdschrift9
DOI's
StatusPublished - 1-sep-2016

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