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Abstract

Objectives: Antibody-mediated rejection in transplant recipients with preexisting donor-specific antibodies is a challenging clinical situation. However, we lack suitable animal models to study this scenario. The aim of this study was to develop an animal model of acute antibody-mediated rejection of renal allografts in sensitized recipients. Materials and Methods: We used major histocompatibility complex class I and II incompatible rat strains (Dark Agouti RT1 av1 and Lewis RT1 l ), which develop aggressive rejection. Recipient Lewis rats were immunized with donor strain spleen cells 5 days before surgery to induce donor-specific antibodies. Rats underwent bilateral nephrectomy and orthotopic transplant of the donor kidney. To minimize T-cellmediated rejection while allowing the development of donor-specific antibodies, recipient animals were given tacrolimus starting the day before surgery. Results: Hyperacute rejection was not seen, but acute graft dysfunction was evident on day 1 with a rapid deterioration of graft function by day 3. Histologic damage featured glomerulopathy, capillaritis, capillary thrombosis, and acute tubular injury. Recipients exhibited high serum levels of donorspecific antibodies and deposition of immunoglobulin G and C4d on graft endothelium. Immunostaining showed substantial endothelial damage, fibrin deposition in glomerular and peritubular capillaries, and infiltrates of macrophages, neutrophils, and natural killer cells. T-cell activation was efficiently suppressed by tacrolimus. Conclusions:We have developed a clinically relevant model of acute antibody-mediated rejection in recipients with preexisting donor-specific antibodies, which is suitable for testing novel therapies.

Auditory brainstem responses in aging dark agouti rats

“…A rat strain that shows promise as a model for studying human hearing loss is the dark agouti (DA) rat [17]. One rationale for examining hearing loss in DA rats has to do with the long-known association between hearing loss and kidney disease; DA rats are known to be susceptible to kidney disease [18][19][20][21][22][23][24], indicating DA rats may also demonstrate susceptibility to hearing loss. For example, in humans there are over 20 known congenital disorders that involve both hearing loss and renal abnormalities, including Alport Syndrome, Branchio-oto-renal syndrome, and Fabry disease [25].…”

Iguratimod Attenuates Macrophage Polarization and Antibody-Mediated Rejection After Renal Transplant by Regulating KLF4

“…The cells were incubated with PE-conjugated anti-rat IgG (GB21302, Servicebio) after cleaning. The mean fluorescence intensity (MFI) of the cell suspension was measured by flow cytometry and the level of serum DSA was evaluated ( Chandran et al, 2018 ; Zhao et al, 2018 ).…”