Background: Kidney transplantation performed in the presence of high-titre donor-specific antibodies (DSA) may result in hyper-acute or accelerated antibody-mediated rejection and rapid allograft loss. Previous studies have shown that this risk may be mitigated with simultaneous liver-kidney transplantation (SLKT); however, the mechanisms are not well defined. Here we report the evolution of pre-formed, high-level DSAs in two highly sensitised SLKT recipients peri-operatively and describe a profound sustained depletion of all DSAs from the time of liver anastomosis with no extra desensitisation therapy required.
Case Presentation: Two patients underwent SLKT and received our centre's standard renal transplant immunosuppression with basiliximab and methylprednisolone for induction therapy and prednisolone, mycophenolate and tacrolimus for maintenance therapy. HLA antibody samples were collected pre-operatively, and immediately post-liver and post-kidney revascularisation, and then regularly in the post-transplant period. Complement Dependant Cytotoxicity (CDC) crossmatches were also performed. Both patients were highly sensitised with a PRA over 97%. One patient had a positive B- and T-cell crossmatch pre-transplant. These positive CDC crossmatches became negative and the level of pre-formed DSAs reduced profoundly and rapidly, within 3 h post-liver revascularisation. The reduction in pre-formed DSAs, regardless of subclass, was seen immediately post-liver revascularisation, before implantation of the renal allografts. No significant reduction in non-donor specific HLA-antibodies was observed. Both patients maintained good graft function with no rejection on kidney allograft protocol biopsies performed at 10-weeks post-transplant.
Conclusions: These cases support the protective immunoregulatory role of the liver in the setting of SLKT, with no extra desensitisation treatment given pre-operatively for these highly sensitised patients.
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http://dx.doi.org/10.1186/s12882-020-01714-y | DOI Listing |
mBio
January 2025
Department of Microbiology and Immunology, University of Iowa, Iowa City, Iowa, USA.
Unlabelled: Post-acute sequelae of COVID-19 involves several organs, but its basis remains poorly understood. Some infected cells in mice survive the acute infection and persist for extended periods in the respiratory tract but not in other tissues. Here, we describe two experimental models of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection to assess the effect of viral virulence on previously infected cells.
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January 2025
Laboratory for Clinical Immunology and Molecular Genetics, University Clinic of Respiratory and Allergic Diseases Golnik, Golnik, Slovenia.
The basophil activation test (BAT) has become a major cellular test for evaluating the allergenic activity of specific IgEs. The impact of the BAT is due to the ability of blood basophil granulocytes to present IgE on the high-affinity FcRI receptor and to mirror the mast cell response that elicits an acute allergic reaction. The BAT proved to be able to identify allergic patients at risk of reacting to a low dose of the allergen and/or developing life-threatening reactions and thus can significantly improve the current management of allergic patients.
View Article and Find Full Text PDFBackground: In high-burden settings, most tuberculosis (TB) transmission likely occurs outside the home. Our qualitative study in Zambia explored the acceptability and preferences for designing TB active case finding (ACF) strategies to reach non-household contacts of people with TB.
Methods: We conducted 56 in-depth interviews with persons with TB ( = 12), TB healthcare workers (HCWs) ( = 10), TB lay HCWs ( = 10), and leaders/owners ( = 12) and attendees ( = 12) of community venue types identified as potential TB transmission locations.
Mol Pharm
January 2025
Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, North Carolina 27402, United States.
The fungal metabolite verticillin A is a potent and selective histone methyltransferase inhibitor. It regulates apoptosis, the cell cycle, and stress response, and displays potent activity in the suppression of tumor cell growth in several different in vivo models. Verticillin A sensitizes pancreatic cancer cells to anti-PD-1 immunotherapy by regulating PD-L1 expression.
View Article and Find Full Text PDFTranspl Int
January 2025
Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium.
Highly sensitized (HS) patients in need of kidney transplantation (KTx) typically spend a longer time waiting for compatible kidneys, are unlikely to receive an organ offer, and are at increased risk of antibody-mediated rejection (AMR). Desensitization using imlifidase, which is more rapid and removes total body immunoglobulin G (IgG) to a greater extent than other methods, enables transplantation to occur between HLA-incompatible (HLAi) donor-recipient pairs and allows patients to have greater access to KTx. However, when the project was launched there was limited data and clinical experience with desensitization in general and with imlifidase specifically.
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