Renal allograft rejection, lymphocyte infiltration, and de novo donor-specific antibodies in a novel model of non-adherence to immunosuppressive therapy

BMC Immunology

Research Article

Helen Poth¹  Louisa Kühne¹  Antonia Schuster¹  Simone Wurm¹  Tobias Bergler¹  Bettina Jung¹  Bernhard Banas¹  Petra Ruemmele² 

[1] Department of Nephrology, University Hospital Regensburg, Franz-Josef-Strauß Allee 11, D-93053, Regensburg, Germany;Department of Pathology, University Hospital Erlangen, Erlangen, Germany;

关键词: Donor specific antibodies;    Humoral rejection;    Renal transplantation;    Non-adherence;    Leukocyte infiltration;    BAFF;   

DOI  :  10.1186/s12865-017-0236-6

 received in 2017-05-26, accepted in 2017-12-07,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundNon-adherence has been associated with reduced graft survival. The aim of this study was to investigate the immunological mechanisms underlying chronic renal allograft rejection using a model of non-adherence to immunosuppressive therapy. We used a MHC (major histocompatibility complex) -mismatched rat model of renal transplantation (Brown Norway to Lewis), in which rats received daily oral cyclosporine A. In analogy to non-adherence to therapy, one group received cyclosporine A on alternating days only. Rejection was histologically graded according to the Banff classification. We quantified fibrosis by trichrome staining and intra-graft infiltration of T cells, B cells, and monocytes/macrophages by immunohistochemistry. The distribution of B lymphocytes was assessed using immunofluorescence microscopy. Intra-graft chemokine, chemokine receptor, BAFF (B cell activating factor belonging to the TNF family), and immunoglobulin G transcription levels were analysed by RT-PCR. Finally, we evaluated donor-specific antibodies (DSA) and complement-dependent cytotoxicity using flow cytometry.ResultsAfter 28 days, cellular rejection occurred during non-adherence in 5/6 animals, mixed with humoral rejection in 3/6 animals. After non-adherence, the number of T lymphocytes were elevated compared to daily immunosuppression. Monocyte numbers declined over time. Accordingly, lymphocyte chemokine transcription was significantly increased in the graft, as was the transcription of BAFF, BAFF receptor, and Immunoglobulin G. Donor specific antibodies were elevated in non-adherence, but did not induce complement-dependent cytotoxicity.ConclusionCellular and humoral rejection, lymphocyte infiltration, and de novo DSA are induced in this model of non-adherence.

【 授权许可】

CC BY   
© The Author(s). 2017