ACPA Specific IVIG Attenuate Collagen Induced Arthritis in Mice

Shaye Kivity¹, Nina Svetliscky¹, Qusim Odeh¹, Smadar Gertel¹, Howard Amital¹, Omer Gendelman¹, Iris Barshack², Alexander Volkov², Eran Bar-Meir³, Miri Blank¹ and Yehuda Shoenfeld⁴, ¹Sheba Medical Center, Zabludowicz Center for Autoimmune Diseases, affiliated to Sackler Faculty of Medicine, Tel-Aviv University, Ramat Gan, Israel, ²Sheba Medical Center, Institute of Pathology, affiliated to Sackler Faculty of Medicine, Tel-Aviv University, Ramat Gan, Israel, ³Plastic surgeon Poria Medical Center affiliated to Faculty of medicine in the Galilee Bar-Ilan university, Poria, Israel, ⁴Sheba Medical Center, Zabludowicz Center for Autoimmune Diseases, affiliated to affiliated to Sackler Faculty of Medicine, Tel-Aviv University, Ramat Gan, Israel

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: ACPA, arthritis management, Intravenous immunoglobulin (IVIG), mouse model and therapeutic targeting

Session Information

Date: Tuesday, November 10, 2015

Title: Rheumatoid Arthritis - Animal Models Poster

Session Type: ACR Poster Session C

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

Background/Purpose:

Administration of intravenous-immunoglobulin (IVIg) is a recognized safe and efficient immunomodulatore therapy for many autoimmune diseases. Anti-idiotypic antibody binding to pathogenic autoantibodies was proposed as one of mechanisms attributed to the protective activity of IVIg in autoimmunity. The aim of this study was to fractionate the anti-anti-citrullinated protein anti-idiotypic-antibodies (anti-ACPA) from a IVIg preparation and to test it as a treatment for collagen-induced arthritis in mice.

Methods:

IVIg was loaded on an ACPA column. The eluted fraction was defined as ACPA-specific-IVIg (ACPA-sIVIg). Collagen-induced-arthritis (CIA) was induced in mice. Mice were treated weekly with ACPA-sIVIg, low-dose-IVIg, high-dose-IVIg and PBS. Sera-ACPA titers, anti-collagen Abs and cytokine levels were analyzed by ELISA; antibody-forming-cell activity by ELIspot assay; expansion of T-regulatory cell (Treg) population by FACS.

Results:

ACPA-sIVIg inhibited ACPA binding to citrullinated-peptides (CCP) in-vitro 100 times more efficiently than the IVIg compound. ACPA-sIVIg was significantly more effective than IVIg-preparation in attenuating development of collagen-induced arthritis. Splenocytes from CIA mice treated with ACPA-sIVIg reduced the ACPA and anti-collagen-antibody titers including the number of anti-collagen and ACPA antibody-forming cells. In parallel, splenocytes from ACPA-sIVIg treated mice secreted higher levels of anti-inflammatory cytokines and lower proinflammatory cytokines. The ACPA-sIVIg inhibitory potential was accompanied with expansion of the Treg population. Low dose IVIg did not affect the humoral and cellular response in the CIA-mice, in comparison to PBS treated mice.

Conclusion:

Based on our results, IVIg may be considered as a safe compound for treating patients with rheumatoid-arthritis by neutralizing pathogenic autoantibodies , reducing proinflammatory cytokines and expanding Treg population.

Disclosure: S. Kivity, None; N. Svetliscky, None; Q. Odeh, None; S. Gertel, None; H. Amital, None; O. Gendelman, None; I. Barshack, None; A. Volkov, None; E. Bar-Meir, None; M. Blank, None; Y. Shoenfeld, None.

To cite this abstract in AMA style:

Kivity S, Svetliscky N, Odeh Q, Gertel S, Amital H, Gendelman O, Barshack I, Volkov A, Bar-Meir E, Blank M, Shoenfeld Y. ACPA Specific IVIG Attenuate Collagen Induced Arthritis in Mice [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/acpa-specific-ivig-attenuate-collagen-induced-arthritis-in-mice/. Accessed .

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