Immunomodulation of Naïve RA Patients PBMCs with a Multi-Epitope Peptide Derived from Citrullinated Autoantigens

Smadar Gertel¹, Yehuda Shoenfeld² and Howard Amital³, ¹Sheba Medical Center, Zabludowicz Center for Autoimmune Diseases, affiliated to Sackler Faculty of Medicine, Tel-Aviv University, Ramat Gan, Israel, ²Head Dept of Medicine B, Sheba Medical Center, Ramat-Gan, Israel, ³Sheba Medical Center, Tel-Hashomer, Israel

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: anti-CCP antibodies, citrullination, cytokines and rheumatoid arthritis (RA)

Session Information

Date: Sunday, November 8, 2015

Title: Rheumatoid Arthritis - Human Etiology and Pathogenesis Poster I

Session Type: ACR Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose:

Citrullinated peptides are major targets of disease-specific autoantibodies in rheumatoid arthritis (RA).

We generated a multi-epitope citrullinated peptide (Cit-ME), derived from major prevalent citrullinated autoantigens (citrullinated filaggrin, β-fibrinogen, vimentin and collagen type II).

Our aim was to test the ability of the Cit-ME peptide to immunomodulate cytokines gene expression and to alter the Treg subset in culture when incubated with peripheral blood mononuclear cells (PBMC) derived from newly diagnosed RA patients

Methods:

Naïve RA-patient’s derived PBMC were incubated in the presence of either the Cit-ME or citrullinated-β-fibrinogen peptide derived from a single prevalent citrullinated autoantigen (1.25µg/ml). Immunomodulation by the peptides was compared to matched non-citrullinated peptides and to traditional biological therapies as Infliximab and Tocalizumab. Following incubation of 24-72 hours with the experimental components we analyzed immune-modulation of cytokines by real-time PCR and analysis of T regulatory population by flow cytometry.

Results:

We found that PBMC from RA patients, incubated in the presence of either Cit-ME or citrullinated-β-fibrinogen, elicited up-regulation of the TGF-β gene expression (16% and 8%, respectively) as compared to the medium control. The Cit-ME elevated the frequencies CD4⁺FoxP3⁺ T cells (18%) as compared to the medium. In addition, both citrullinated peptides were shown to down-regulate the mRNA expression of the pathogenic cytokines TNF-α and IL-1β. Furthermore we found that the citrullinated peptides were more effective in downregulating the inflammatory state of the PMMC as compared to the effect of the biological agents.

Conclusion:

Citrullinated autoantigens can immunomodulate the inflammatory response in PBMC of patients with RA in culture.

Disclosure: S. Gertel, None; Y. Shoenfeld, None; H. Amital, None.

To cite this abstract in AMA style:

Gertel S, Shoenfeld Y, Amital H. Immunomodulation of Naïve RA Patients PBMCs with a Multi-Epitope Peptide Derived from Citrullinated Autoantigens [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/immunomodulation-of-naive-ra-patients-pbmcs-with-a-multi-epitope-peptide-derived-from-citrullinated-autoantigens/. Accessed .

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