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Mediators of Inflammation
Volume 2017, Article ID 3916519, 9 pages
https://doi.org/10.1155/2017/3916519
Research Article

Immunomodulation of RA Patients’ PBMC with a Multiepitope Peptide Derived from Citrullinated Autoantigens

1Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, 5262100 Ramat-Gan, Israel
2Sackler Faculty of Medicine, Tel-Aviv University, 6997801 Tel-Aviv, Israel
3Department of Internal Medicine B, Sheba Medical Center, 5262100 Tel Hashomer, Israel
4Unité Différenciation Epithéliale et Autoimmunité Rhumatoïde, Université de Toulouse-INSERM, Toulouse, France
5Laboratoire de Biologie Cellulaire et Cytologie, CHU de Toulouse, Toulouse, France
6Incumbent of the Laura Schwarz-Kipp Chair for Research of Autoimmune Diseases, Tel Aviv University, 6997801 Tel Aviv, Israel

Correspondence should be addressed to Smadar Gertel; li.vog.htlaeh.abehs@letreg.radams

Received 23 January 2017; Revised 19 April 2017; Accepted 11 May 2017; Published 21 June 2017

Academic Editor: Tânia Silvia Fröde

Copyright © 2017 Smadar Gertel et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Citrullinated peptides are used for measuring anticitrullinated protein antibodies (ACPA) in rheumatoid arthritis (RA). Accumulation of citrullinated proteins in the inflamed synovium suggests that they may be good targets for inducing peripheral tolerance. In view of the multiplicity of citrullinated autoantigens described as ACPA targets, we generated a multiepitope citrullinated peptide (Cit-ME) from the sequences of major citrullinated autoantigens: filaggrin, β-fibrinogen, vimentin, and collagen type II. We assessed the ability of Cit-ME or the citrullinated β60-74 fibrinogen peptide (β60-74-Fib-Cit) which bears immunodominant citrullinated epitopes (i) to modify cytokine gene expression and (ii) to modulate Treg and Th17 subsets in PBMC derived from newly diagnosed untreated RA patients. RA patient’s PBMC incubated with Cit-ME or β60-74-Fib-Cit, showed upregulation of TGF-β expression (16% and 8%, resp.), and increased CD4+Foxp3+ Treg (22% and 19%, resp.). Both peptides were shown to downregulate the TNF-α and IL-1β expression; in addition, Cit-ME reduced CD3+IL17+ T cells. We showed that citrullinated peptides can modulate the expression of anti- and proinflammatory cytokines in PBMC from RA patients as well as the proportions of Treg and Th17 cells. These results indicate that citrullinated peptides could be active in vivo and therefore might be used as immunoregulatory agents in RA patients.