B-cell Deficiency Attenuates Transplant Glomerulopathy in a Rat Model of Chronic Active Antibody-mediated Rejection.

Autor:	Reese SR; Division of Nephrology, Department of Medicine, University of Wisconsin, Madison, WI., Wilson NA; Division of Nephrology, Department of Medicine, University of Wisconsin, Madison, WI., Huang Y; Department of Pathology, Renmin Hospital of Wuhan University, Wuchang District, Wuhan, China., Ptak L; Division of Nephrology, Department of Medicine, University of Wisconsin, Madison, WI., Degner KR; Division of Nephrology, Department of Medicine, University of Wisconsin, Madison, WI., Xiang D; Department of Organ Transplantation, Xiangya Hospital, Central South University, Changsha, Hunan, China., Redfield RR; Division of Transplant Surgery, Department of Surgery, University of Wisconsin, Madison, WI., Zhong W; Department of Pathology, University of Wisconsin, Madison, WI., Panzer SE; Division of Nephrology, Department of Medicine, University of Wisconsin, Madison, WI.
Jazyk:	angličtina
Zdroj:	Transplantation [Transplantation] 2021 Jul 01; Vol. 105 (7), pp. 1516-1529.
DOI:	10.1097/TP.0000000000003530
Abstrakt:	Background: Transplant glomerulopathy (TG) is a pathological feature of chronic active antibody-mediated rejection (cAMR) and is associated with renal allograft failure. The specific role of B cells in the pathogenesis of TG is unclear. Methods: We used a minor mismatched rat kidney transplant model with B cell-deficient recipients, generated by clustered regularly interspaced short palindromic repeats/Cas9 technology, to investigate the impact of B-cell depletion on the pathogenesis of TG. We hypothesized that B-cell deficiency would prevent TG in the rat kidney transplant model of cAMR. Treatment groups included syngeneic, allogeneic, sensitized allogeneic, and B cell-deficient allogeneic transplant recipients. Results: B cell-deficient recipients demonstrated reduced TG lesions, decreased microvascular inflammation, reduced allograft infiltrating macrophages, and reduced interferon gamma transcripts within the allograft. Allograft transcript levels of interferon gamma, monocyte chemoattractant protein-1, and interleukin-1β correlated with numbers of intragraft macrophages. B cell-deficient recipients lacked circulating donor-specific antibodies and had an increased splenic regulatory T-cell population. Conclusions: In this model of cAMR, B-cell depletion attenuated the development of TG with effects on T cell and innate immunity. Competing Interests: The authors declare no conflicts of interest. (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)
Databáze:	MEDLINE
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