Date: Sunday, June 2, 2019
Session Name: Concurrent Session: B-cell / Antibody /Autoimmunity
Session Time: 4:30pm-6:00pm
Presentation Time: 4:42pm-4:54pm
Location: Room 310
*Purpose: Our study was designed to investigate the efficacy and related mechanisms of Iguratimod (T-614) in the inhibition of DSAs following kidney transplantation.
*Methods: A rat renal transplant ABMR model was established. Levels of de novo DSAs following skin transplant and renal transplant were detected by flow cytometry assay. Levels of Bregs (CD19+Tim-1+), Tregs (CD4+CD25+ Foxp3+), as well as the Th17 cells (CD4+IL-17A+), in peripheral blood monocytes (PBMCs) collected from recipients were also examined. Various inflammatory cytokines, such as IL-2, IL-4, IL-10, and IL-17, were tested by ELISA assay. To further explore the mechanism involved, primary Bregs were extracted from the spleen of recipients and co-cultured with PBMCs of recipients in vitro. De novo DSAs were detected. Moreover, the Bregs and balance of Th17/Tregs were examined.
*Results: We found that the administration of Iguratimod could induce the significant reduction of de novo DSAs in skin transplant and secondary DSAs following renal transplant. Moreover, the allograft function was remarkably improved in the treatment of Iguratimod. To further explore the related mechanisms, flow cytometry assay showed the significantly increased expression of Tregs, as well as the decreased expression of Th17 cells. Furthermore, our primary results from randomized controlled trials in our renal transplant center also supported the favorable efficacy of Iguratimod on decreasing the production of DSAs in sensitized renal transplant recipients, as well as the imbalance of Th17/Tregs.
*Conclusions: As a result, our study concluded that Iguratimod could significantly inhibit the production of DSAs and the progression of ABMR following renal transplant by modulating the imbalance of Th17/Treg.
To cite this abstract in AMA style:Wang Z, Zheng M, Chen H, Li S, Han Z, Tao J, Ju X, Tan R, Gu M. Iguratimod Inhibits the Donor Specific Antibodies Production and Attenuates the Antibody Mediated Rejection in Rat Kidney Transplantation [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/iguratimod-inhibits-the-donor-specific-antibodies-production-and-attenuates-the-antibody-mediated-rejection-in-rat-kidney-transplantation/. Accessed December 12, 2019.
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