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Abstract Number: 647

Helminthes Derivative for Treating Lupus and Colitis in Mice Models

Miri Blank1, Tomer Bashi1, Dana Ben-Ami Shor1, Mati Fridkin2, Iris Barshack3, Alexander Volkov4 and Yehuda Shoenfeld1, 1Zabludowicz Center for Autoimmune Diseases, Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, affiliated to Sackler Faculty of Medicine, Tel-Aviv University, Ramat Gan, Israel, 2Organic Chemistry, Weizmann Institute for Sciences, Rehovot, Israel, 3Institute of Pathology, Sheba Medical Center, affiliated to Sackler Faculty of Medicine, Tel-Aviv University,Tel-Aviv, Tel-Aviv, Israel, 4Institute of Pathology, Sheba Medical Center, affiliated to Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Tel-Aviv, Israel

Meeting: ACR/ARHP Annual Meeting 2014

Keywords:

Session Information

Title: Systemic Lupus Erythematosus - Animal Models

Session Type: Abstract Submissions (ACR)

Background/Purpose:  In areas where helminthes infections are common, autoimmune diseases are rare. Treatment with ova from helminthes, improved clinical findings of inflammatory bowel disease and other autoimmune diseases.  The tolerogenic properties of the helminthes and their ova were attributed to the phosphorylcholine (PC) molecule. We aimed to decipher the tolerogenic potential of Tuftsin-PC (TPC) compound  in experimental Lupus and Colitis.                                                                    

Methods: 1. Lupus prone NZBXW/F1 mice received subcutaneously TPC (5µg/ml), 3 times a week using preventive protocol. Autoantibodies were tested by ELISA, T-regulatory-cells by FACS, cytokines by RT-PCR and R&D ELISA DuoSet. Glomerulonephritis was addressed by the presence of proteinuria, PAS staining and immunoglobulin deposition in the mesangium by immunofluorescence. 2. Colitis was induced by Dextran-Sodium-Sulfate (DSS) in drinking water. TPC was given by daily oral ingestion (500 µg/mouse or PBS) starting at day (-2). DAI score was followed daily and histology of the colon was performed by H&E staining.                                                                             

Results: 1. Lupus  mice treated with TPC attenuated the development of glomerulonephritis, illustrated  by a significant diminished proteinuria (p<0.02), and reduced immunoglobulin deposits in the kidney mesangium. TPC enhanced expression of TGFbeta and IL-10  (p<0.001), and inhibited  anti-inflammatory cytokines profile on the level of protein and RT-PCR. Significant enhancement of CD4+CD25+FOXP3+ T-regulatory cells phenotype was documented.  2. Chemically induced colitic mice, treated with TPC, developed a significant moderate colitis, in comparison to mice which received the vehicle. The DAI score of the TPC treated mice was 0.9, whereas DAI score of  2.6 was observed in colitis mice which received the vehicle, p<0.02. The reduced DAI score in the TPC group was associated with a significant colon shortening and prevention of colon destruction as observed by histological analyses.   

Conclusion: TPC delayed lupus development in lupus prone mice and prevented a significant colitis induction in naïve mice. 

 

Disclosure:

M. Blank,
None;

T. Bashi,
None;

D. Ben-Ami Shor,
None;

M. Fridkin,
None;

I. Barshack,
None;

A. Volkov,
None;

Y. Shoenfeld,
None.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/helminthes-derivative-for-treating-lupus-and-colitis-in-mice-models/