Long-term allograft survival in allotransplantation, especially in kidney and heart transplantation, is mainly limited by the occurrence of antibody-mediated rejection due to anti-Human Leukocyte Antigen antibodies. These types of rejection are difficult to handle and chronic endothelial damages are often irreversible. In the settings of ABO-incompatible transplantation and xenotransplantation, the presence of antibodies targeting graft antigens is not always associated with rejection. This resistance to antibodies toxicity seems to associate changes in endothelial cells phenotype and modification of the immune response. We describe here these mechanisms with a special focus on endothelial cells resistance to antibodies. Endothelial protection against anti-HLA antibodies has been described and in animal models, but do not seem to be a common feature in immunized allograft recipients. Complement regulation and anti-apoptotic molecules expression appear to be common features in all these settings. Lastly, pharmacological interventions that may promote endothelial cell protection against donor specific antibodies will be described.
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http://dx.doi.org/10.3389/fimmu.2022.932242 | DOI Listing |
Proc Natl Acad Sci U S A
January 2025
Laboratory of Precision Medicine and Biopharmaceuticals, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
Recurrent missense mutations in the human epidermal growth factor receptor 2 (HER2) have been identified across various human cancers. Among these mutations, the active S310F mutation in the HER2 extracellular domain stands out as not only oncogenic but also confers resistance to pertuzumab, an antibody drug widely used in clinical cancer therapy, by impeding its binding. In this study, we have successfully employed computational-aided rational design to undertake directed evolution of pertuzumab, resulting in the creation of an evolved pertuzumab variant named Ptz-SA.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Division of Livestock Infectious Diseases, State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, China.
Historically considered to be nonenveloped, hepatitis E virus (HEV), an important zoonotic pathogen, has recently been discovered to egress from infected cells as quasi-enveloped virions. These quasi-enveloped virions circulating in the blood are resistant to neutralizing antibodies, thereby facilitating the stealthy spread of infection. Despite abundant evidence of the essential role of the HEV-encoded ORF3 protein in quasi-enveloped virus formation, the underlying mechanism remains unclear.
View Article and Find Full Text PDFJ Am Chem Soc
January 2025
Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands.
is a Gram-positive bacterium that is responsible for severe nosocomial infections. The rise of multidrug-resistant strains, which can pose significant health threats, prompts the development of new treatment interventions, and much attention has been directed at the development of prophylactic and therapeutic vaccination strategies. Capsular polysaccharides (CPs) are key protective elements of the cell wall and have been proposed as promising candidate antigens.
View Article and Find Full Text PDFAdv Sci (Weinh)
January 2025
Translational Medical Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450001, China.
Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by reduced platelet levels and heightened susceptibility to bleeding resulting from augmented autologous platelet destruction and diminished thrombopoiesis. Although antibody-mediated autoimmune reactions are widely recognized as primary factors, the precise etiological agents that trigger ITP remain unidentified. The pathogenesis of ITP remains unclear owing to the absence of comprehensive high-throughput data, except for the belated emergence of autoreactive antibodies.
View Article and Find Full Text PDFJ Cancer Res Ther
December 2024
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China.
Background: Patients with transplant-ineligible relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) have limited treatment options and poor outcomes.
Methods: This phase III study (NCT04236141) evaluated the efficacy and safety of polatuzumab vedotin plus bendamustine and rituximab (Pola+BR) versus BR in Chinese patients with transplant-ineligible R/R DLBCL to support regulatory submission in China. Patients were randomized 2:1 to receive Pola+BR or placebo+BR.
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