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Abstract Number: 2061

Successful Treatment of Murine Lupus Nephritis with Helminths Related  Tuftsin-Phosphorylcholine Compound and Its Effect on the Microbiota

Yehuda Shoenfeld1, Tomer Bashi2, Hadar Gershon3, Or Givol4, Alexander Volkov5, Iris Barshack5, Mati Fridkin6, Miri Blank2 and Omry Koren7, 1Zabludowicz Center for Autoimmune Diseases, Chaim Sheba Medical Center, Tel Hashomer, Israel Incumbent of the Laura Schwarz-Kipp Chair for Research of Autoimmune Diseases, Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel, 2Sheba Medical Center, Zabludowicz Center for Autoimmune Diseases, affiliated to affiliated to Sackler Faculty of Medicine, Tel-Aviv University, Ramat Gan, Israel, 3Sefat Medical School, Bar-Ilan University, Sefat, Israel, 4Zabludowicz Center for Autoimmune Diseases, Ramat Gan, Israel, 5Sheba Medical Center, Institute of Pathology, affiliated to Sackler Faculty of Medicine, Tel-Aviv University, Ramat Gan, Israel, 6Organic chemistry, Weizmann Institute for Sciences, Rehovot, Israel, 7Sefat medical school, Bar-Ilan university, Sefat, Israel

Meeting: 2016 ACR/ARHP Annual Meeting

Date of first publication: September 28, 2016

Keywords: Animal models, drug treatment, Lupus nephritis, microbiome and treatment

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Session Information

Date: Monday, November 14, 2016

Title: Systemic Lupus Erythematosus – Animal Models

Session Type: ACR Concurrent Abstract Session

Session Time: 4:30PM-6:00PM

Background/Purpose: , In areas where helminths infections are common, autoimmune diseases are rare. Treatment with helminthes and their ova, improved clinical findings of inflammatory bowel disease, multiple sclerosis and rheumatoid-arthritis. The immunomodulatory functions of some helminths were attributed to the phosphorylcholine (PC) moiety. We aimed to decipher the tolerogenic potential of Tuftsin-PC (TPC) compound in mice genetically prone to develop lupus when the disease was already established. In addition we analyzed the microbiota, assuming that it may be affected by TPC treatment on lupus development.

Methods: , Lupus prone NZBXW/F1 mice received subcutaneously TPC (5 mg/1 ml), 3 times a week starting at 24 weeks of age, when proteinuria showed 10 mg/dl. At this point feces were collected weekly. Autoantibodies were tested by ELISA,  cytokines secretion by splenocytes in-vitro using DuoSet ELISA, T-regulatory-cells by FACS. Glomerulonephritis was addressed by detection of proteinuria, and immunoglobulin complex deposition in the mesangium of the kidneys of the mice by immunofluorescence. Stools from the mice were collected every 3 days for microbiome analyses. DNA was extracted from the stools and then sequenced using Illumina Miseq platform.  Data analysis was performed using QIIME.

Results: Our results show that TPC treatment attenuated the development of glomerulonephritis in lupus prone mice, manifested by reduced proteinuria and immunoglobulin deposition in the kidney mesangium. TPC also increased the expression of IL-10 (p < 0.001), and inhibited the production of IFNg , IL-1b and IL-17 (p < 0.03). TPC significantly expanded  CD4+CD25+FOXP3+ T-regulatory cells (Tregs) phenotype in the treated mice. The microbiota analyses showed that TPC exhibited a marked depletion of Akkermansia (specifically muciniphila species) and higher abundance of Odoribacter compared to PBS treated mice, which correlated to proteinuria levels. Generally, high protein secretions correlated with an increased abundance of four bacteria genera; Akkermansia AF12, S24-7, Bacteroides, and one bacteria order Clostridiales. High protein levels were correlated also with decreased levels of thirty three additional otus, with the Odoribacter genus among them.               

Conclusion: Our data indicate that TPC treatment inhibits lupus nephritis development in genetically lupus prone mice, attenuates pro-inflammatory cytokines and enhance anti-inflammatory IL-10 expression, as well as Tregs expansion. The results propose harnessing novel natural therapy for lupus patients. In addition our results show that TPC significantly alters the microbiota composition which correlated with decreased protein levels in the urine.


Disclosure: Y. Shoenfeld, None; T. Bashi, None; H. Gershon, None; O. Givol, None; A. Volkov, None; I. Barshack, None; M. Fridkin, None; M. Blank, None; O. Koren, None.

To cite this abstract in AMA style:

Shoenfeld Y, Bashi T, Gershon H, Givol O, Volkov A, Barshack I, Fridkin M, Blank M, Koren O. Successful Treatment of Murine Lupus Nephritis with Helminths Related  Tuftsin-Phosphorylcholine Compound and Its Effect on the Microbiota [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/successful-treatment-of-murine-lupus-nephritis-with-helminths-related-tuftsin-phosphorylcholine-compound-and-its-effect-on-the-microbiota/. Accessed .
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