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A novel complement-fixing IgM antibody targeting GPC1 as a useful immunotherapeutic strategy for the treatment of pancreatic ductal adenocarcinoma.
J Transl Med
November 2023
Experimental and Clinical Pharmacology, Centro Di Riferimento Oncologico (CRO) Di Aviano IRCCS, 33081, Aviano, Italy.
Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers with a very low survival rate at 5 years. The use of chemotherapeutic agents results in only modest prolongation of survival and is generally associated with the occurrence of toxicity effects. Antibody-based immunotherapy has been proposed for the treatment of PDAC, but its efficacy has so far proved limited.
View Article and Find Full Text PDFClinical Outcome of Kidney Transplant Recipients with C1q-Binding De Novo Donor Specific Antibodies: A Single-Center Experience.
J Clin Med
July 2023
Clinic of Nephrology and Renal Transplantation, National and Kapodistrian University of Athens Medical School, Laiko Hospital, 11527 Athens, Greece.
Complement activation by HLA antibodies is a key component of immune-mediated graft injury. We examined the clinical outcomes of kidney transplant recipients with complement-fixing de novo donor-specific antibodies (dnDSA) who were followed in our center. The C1q-binding ability was retrospectively assessed in 69 patients with dnDSA and mean fluorescence intensity (MFI) values > 2000 out of the 1325 kidney transplant recipients who were screened for DSA between 2015 and 2019.
View Article and Find Full Text PDFComplement Binding Anti-HLA Antibodies and the Survival of Kidney Transplantation.
J Clin Med
March 2023
Departamento de Bioquímica, Biología Molecular e Inmunología III, University of Granada, 18010 Granada, Spain.
Background: Antibody-mediated rejection (AMR) is one of the most important challenges in the context of renal transplantation, because the binding of de novo donor-specific antibodies (dnDSA) to the kidney graft triggers the activation of the complement, which in turn leads to loss of transplant. In this context, the objective of this study was to evaluate the association between complement-fixing dnDSA antibodies and graft loss as well as the possible association between non-complement-fixing antibodies and transplanted organ survival in kidney transplant recipients.
Methods: Our study included a cohort of 245 transplant patients over a 5-year period at Virgen de las Nieves University Hospital (HUVN) in Granada, Spain.
Antibodies Produced in Response to a Live-Attenuated Dengue Vaccine Are Functional in Activating the Complement System.
J Infect Dis
May 2023
VBU Discovery Research, Takeda Vaccines, Inc, Cambridge, Massachusetts, USA.
Background: Antibody-driven complement system (CS) activation has been associated with protection against symptomatic dengue virus (DENV) infection. Aggregation, opsonization, lysis, and phagocytosis are mechanisms triggered by antibody-antigen immunocomplexes following fixation of the component 1q (C1q) and activation of the classical pathway. As a result, DENV neutralization and clearance are facilitated, whereas antibody-dependent enhancement of infection is inhibited.
View Article and Find Full Text PDFComplement component C3 and C5b-9 deposition on hypoxia reperfused endothelial cells by non-HLA antibodies against RhoGDI2: A player involved in graft failure?
HLA
February 2023
Center for Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
Antibodies against Rho GDP-dissociation inhibitor 2 (RhoGDI2) are associated with inferior graft survival in transplant patients receiving a kidney from deceased donors. Although this suggests that these antibodies contribute to graft injury because of ischemia, it remains unknown whether they are also pathogenically involved in the process of graft loss. To study this, we firstly analyzed the IgG subclass profile of anti-RhoGDI2 antibodies in kidney transplant recipients, and whether antibody titers change over time or because of acute rejection.
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