Background: The immunological mechanisms of graft rejections after penetrating keratoplasty are largely investigated in rodent models. Here, antigens are predominantly processed by host antigen presenting cells (APCs). For this reason, graft rejections are not primarily triggered by mismatches in the major histocompatibility complex (MHC). Consequently, MHC matching (equivalent of HLA matching) does not robustly prevent immunological graft rejections in mice. This, however, may not apply to humans because anatomy and the clinical picture of immune reactions differ vastly.
Methods: Immunological experiments are not feasible in humans for ethical reasons. However, the recent surgical modifications in keratoplasty inadvertently gave rise to several interesting immunological field experiments. We herein discuss the potential insight into human graft rejections from selected clinical observations. On this basis, we have evaluated HLA matching for keratoplasty techniques.
Results: Several clinical observations hint towards an active role of donor-derived APCs in graft rejections after human keratoplasty. Additionally, donor-specific anti-HLA antibodies may play a significant role. On this basis we suggest that HLA matching is potentially beneficial in human keratoplasty in contrast to the situation in mice.
Conclusions: Graft rejections are rarely observed after Descemet membrane keratoplasty (DMEK). For this reason, we do not recommend HLA matching here. The same is true for deep anterior lamellar keratoplasty, where graft rejections can usually be treated well. However, HLA matching is a viable option in penetrating keratoplasty. This is especially true for high-risk eyes.
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http://dx.doi.org/10.1055/s-0032-1328256 | DOI Listing |
PLoS One
January 2025
Faculty of Veterinary Science, Veterinary Clinical Stem Cell and Bioengineering Research Unit, Chulalongkorn University, Bangkok, Thailand.
Potential trend of regenerative treatment for type I diabetes has been introduced for more than a decade. However, the technologies regarding insulin-producing cell (IPC) production and transplantation are still being developed. Here, we propose the potential IPC production protocol employing mouse gingival fibroblast-derived induced pluripotent stem cells (mGF-iPSCs) as a resource and the pre-clinical approved subcutaneous IPC transplantation platform for further clinical confirmation study.
View Article and Find Full Text PDFRadiographics
February 2025
From the Department of Radiology (S.Q., R.C., J.C.C., M.M., B.D.A., R.A.) and the Division of Cardiology, Department of Medicine (V.A., J.E.W., R.L.W., D.C.L.), Northwestern University Feinberg School of Medicine, 737 N Michigan Ave, Ste 1600, Chicago, IL 60611; Prince Charles Hospital, Chermside, Queensland, Australia (V.A.); and the Department of Biomedical Engineering, McCormick School of Engineering, Northwestern University, Chicago, Ill (M.M.).
Orthotopic heart transplant (OHT) is a well-established therapy for end-stage heart failure that leads to improved long-term survival rates, with careful allograft surveillance essential for optimizing clinical outcomes after OHT. Unfortunately, complications can arise after OHT that can compromise the success of the OHT. Cardiac MRI is continually evolving, with a range of advanced techniques that can be applied to evaluate allograft structure and function.
View Article and Find Full Text PDFCurr Opin Organ Transplant
January 2025
Division of Nephrology, Virginia Commonwealth University, Richmond, Virginia, USA.
Purpose Of The Review: Calcineurin inhibitors (CNIs) are central to immunosuppression in kidney transplantation (KT), improving short-term outcomes but falling short in enhancing long-term outcomes due to cardiovascular, metabolic, and renal complications. Belatacept, an FDA-approved costimulation blocker, offers a less toxic alternative to CNIs but is limited by its intravenous administration and reduced efficacy in high-immunological-risk patients.
Recent Findings: Emerging therapies target more specific pathways to improve efficacy and accessibility.
Front Immunol
January 2025
Unité Mixte de Recherche (UMR) 7365 Centre National de la Recherche Scientifique (CNRS), Ingénierie Moléculaire, Cellulaire et Physiopathologie (IMoPA), Université de Lorraine, Nancy, France.
CAR-T cell therapy has revolutionized immunotherapy but its allogeneic application, using various strategies, faces significant challenges including graft-versus-host disease and graft rejection. Recent advances using Virus Specific T cells to generate CAR-VST have demonstrated potential for enhanced persistence and antitumor efficacy, positioning CAR-VSTs as a promising alternative to conventional CAR-T cells in an allogeneic setting. This review provides a comprehensive overview of CAR-VST development, emphasizing strategies to mitigate immunogenicity, such as using a specialized TCR, and approaches to improve therapeutic persistence against host immune responses.
View Article and Find Full Text PDFClin J Am Soc Nephrol
January 2025
Erasmus MC Transplant Institute, Department of Surgery, Division of HPB & Transplant Surgery, Erasmus University Medical Center, Rotterdam, The Netherlands.
Background: KEPs (kidney exchange programs) facilitate living donor kidney transplantations (LDKT) for patients with incompatible donors, who are typically higher risk than non-KEP patients because of higher sensitization and longer dialysis vintage. We conducted a comparative analysis of graft outcomes and risk factors for both KEP and non-KEP living donor kidney transplants.
Methods: All LDKTs performed in the Netherlands between 2004-2021 were included.
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