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A Mouse Model of Non-MHC Mismatches Recapitulates Chronic Allograft Dysfunction and I-IFTA

V. Pavlov1, F. Garzon1, R. Haroon Al Rasheed2, K. Banu1, F. ElSalem1, L. Li1, E. Cody1, M. Planoutene1, N. Chun1, Z. Zhang1, J. Leventhal1, B. Murphy1, P. Heeger1, M. C. Menon1

1Medicine, Mount Sinai School of Medicine, New York, NY, 2Pathology, Mount Sinai School of Medicine, New York, NY

Meeting: 2020 American Transplant Congress

Abstract number: D-052

Keywords: Fibrosis, Kidney transplantation, Minor histocompatibility antigens, Preclinical trails

Session Information

Date: Saturday, May 30, 2020

Session Name: Poster Session D: Kidney Complications: Immune Mediated Late Graft Failure

Session Time: 3:15pm-4:00pm

 Presentation Time: 3:30pm-4:00pm

Location: Virtual

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*Purpose: Fibrotic and atrophic changes or IF/TA is an important cause of graft loss. We reported that genome-wide donor-recipient non-HLA mismatches independently correlate with Banff chronic dysfunction scores and decreased graft survival.

*Methods: To test our hypothesis that non-MHC mismatches mediate renal allograft survival via IF/TA, we utilized BALB/c mice congenic for H2b MHC (Bb mice) as kidney donors to Bb, BALB/c (H2d, Bc) and B6 (H2b) recipients, to model syngeneic, MHC mismatched, and non-MHC mismatched renal transplants (N=2 vs 3 vs 4). All graft recipients underwent simultaneous bilateral native nephrectomy making recipients dependent on donor kidney.

*Results: Syngeneic Bb recipients gained weight post-operatively till termination (7wks); Bc recipients had highest rate of weight loss (1A) and least survival (1B). Grafts in Bc & B6 recipients had increased Banff i, t, ti scores vs syngeneic controls (1C); however, Bc recipients had severe acute tubular and vascular injury and formed detectable donor specific antibody to Bb thymocytes vs B6/Bb recipients. At termination, B6 recipients had significantly elevated BUN (106.6±2.7 vs 49.2.6±1.3 mg/dl), and significantly higher Banff chronic scores ie Ci, Ct, mm and I-IFTA scores vs Bb (1D), confirmed by Masson trichrome stain (2). Non MHC antibodies against kidney tissue are being tested currently.

*Conclusions: Our data provides proof that donor-recipient non-mHC mismatch induces chronic renal allograft dysfunction and I-IF/TA and provides a unique model for validating individual novel non-mHC loci and testing therapies for Chronic allograft injury.

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To cite this abstract in AMA style:

Pavlov V, Garzon F, Rasheed RHaroonAl, Banu K, ElSalem F, Li L, Cody E, Planoutene M, Chun N, Zhang Z, Leventhal J, Murphy B, Heeger P, Menon MC. A Mouse Model of Non-MHC Mismatches Recapitulates Chronic Allograft Dysfunction and I-IFTA [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/a-mouse-model-of-non-mhc-mismatches-recapitulates-chronic-allograft-dysfunction-and-i-ifta/. Accessed January 27, 2021.

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