Increasing evidence suggests a detrimental effect of donor-specific antibodies directed against the human leukocyte antigen (HLA)-A, -B, and -DR loci on renal allograft outcomes. Limited data exist on the impact of de novo HLA-DQ antibodies. Over a 3-year period, we prospectively monitored 347 renal transplant recipients without pre-transplant donor-specific antibodies for their development de novo. After 26 months of follow-up, 62 patients developed donor-specific antibodies, of which 48 had a HLA-DQ antibody either alone (33 patients) or in combination with an HLA-A, -B, or -DR antibody (15 patients). Only 14 patients developed a donor-specific HLA-A, -B, or -DR antibody without a HLA-DQ antibody present. Acute rejection occurred in 21% of the HLA-DQ-only patients, insignificant when compared with 11% of patients without donor-specific antibodies. At the last follow-up, the mean serum creatinine and the fraction of patients with proteinuria were significantly higher in those that developed only HLA-DQ than those without antibodies. The 3-year graft survival was significantly worse when HLA-DQ antibodies were combined with non-DQ antibodies (52%) compared with HLA-DQ alone, non-DQ antibodies alone, or no antibodies (92-94%). Thus, our prospective monitoring study found that donor-specific HLA-DQ antibodies were the most common type detected and these antibodies may contribute to inferior graft outcomes. Ongoing surveillance is necessary to determine the long-term outcome of patients developing HLA-DQ donor-specific antibodies.
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http://dx.doi.org/10.1038/ki.2012.190 | DOI Listing |
Transpl Int
January 2025
Department of Nephrology, University Hospital Zurich, Zurich, Switzerland.
The molecular HLA epitope mismatch is an advanced measure for developing donor-specific antibodies (dnDSA) after kidney transplantation. Its relevance in simultaneous pancreas/kidney transplant recipients (SPKTRs) remains unclear. We investigated dnDSA development in 72 SPKTRs and 383 kidney transplant recipients (KTRs) and used the Predicted Indirectly Recognizable HLA-Epitopes (PIRCHE-II) algorithm to calculate the mismatch load of HLA-derived epitopes in total, per HLA-class, and per HLA-locus.
View Article and Find Full Text PDFLong-term allograft survival is limited by humoral-associated chronic allograft rejection, suggesting inadequate constraint of humoral alloimmunity by contemporary immunosuppression. Heterogeneity in alloreactive B cells and the incomplete definition of which B cells participate in chronic rejection in immunosuppressed transplant recipients limits our ability to develop effective therapies. Using a double-fluorochrome single-HLA tetramer approach combined with single-cell culture, we investigated the B-cell receptor (BCR) repertoire characteristics, avidity, and phenotype of donor HLA-DQ reactive B cells in a transplant recipient with end-stage donor specific antibody (DSA)-associated cardiac allograft vasculopathy while receiving maintenance immunosuppression (tacrolimus, mycophenolate mofetil, prednisone).
View Article and Find Full Text PDFSci Immunol
December 2024
Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University Clayton, Victoria, Australia.
T cell activity is governed by T cell receptor (TCR) signaling and constrained by immune checkpoint molecules, including programmed cell death protein 1 (PD-1), cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), and lymphocyte activation gene 3 (LAG-3). The basis for how LAG-3 binds to human leukocyte antigen class II molecules (HLA-II) remains unknown. Here, we present the 3.
View Article and Find Full Text PDFHaematologica
December 2024
Department of Molecular Hematology, Sanquin Research and Landsteiner Laboratory, Amsterdam, The Netherlands; Department of Experimental V ascular Medicine, Amsterdam University Medical C enter, Amsterdam.
The development of neutralizing antibodies (inhibitors) against coagulation factor VIII (FVIII) poses a major challenge in hemophilia A (HA) treatment. The formation of FVIII inhibitors is a CD4+ T-cell dependent mechanism which includes antigen presenting cells (APCs), B- and T-helper lymphocytes. APCs present FVIII derived peptides on major histocompatibility complex class II (MHC-II) to CD4+ Tcells.
View Article and Find Full Text PDFHLA
December 2024
Department of Renal Medicine and Transplantation, Sir Charles Gairdner Hospital, Perth, Australia.
HLA-compatibility remains an important triage test for deceased donor kidney allocation. Low-intermediate resolution donor HLA-typing is typically available at allocation, but its accuracy in assigning pre-transplant donor-specific anti-HLA antibody (DSA) and HLA mismatches compared to 2-field high-resolution typing is poorly characterised. Consecutive deceased donor/recipient pairs from a single centre between 2016 and 2020 were included.
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