Donor-specific antibody (DSA) is an independent risk factor for antibody-mediated rejection (ABMR) and graft loss. The C1q assay differentiates complement from non-complement-binding DSA and C1q-binding DSA may lead to poor allograft survival. Our aim was to characterize the type of DSA seen in pediatric kidney transplant recipients and to determine whether complement binding DSA was associated with inferior graft survival.This was a single-center retrospective study of 48 children who were transplanted between 2009 and 2016. DSA were monitored using Luminex single antigen beads. A negative crossmatch was required to proceed with transplantation. The median follow-up time was 4.9 (3.4, 7.9) years. The median age was 12 (5.7, 15.4) years. DSA developed in 27/48 (56.3%), while C1q-binding DSA developed in 17/27 (63%). There were no significant differences between DSA negative, C1q-binding DSA, and C1q negative DSA, with regard to the number of HLA-ABDR (P = .09) or HLA-DQ mismatches alone (P = .16). For both C1q negative and C1q-binding DSA, DQ was the most common target of the DSA (19/27; 70.4%). C1q-binding DSA was associated with a significantly higher frequency of biopsy proven rejection (76.5%) when compared to C1q negative (10%) and DSA negative (14.3%); P = .001. Graft loss was seen in 6 (12.5%), all of whom had C1q-binding DSA (P = .004). C1q-binding DSA was most commonly directed to DQ antigens. C1q-binding DSA was associated with increased rejection and graft loss. Monitoring for C1q-binding DSA may risk stratify recipients and guide physician management.
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http://dx.doi.org/10.1111/petr.13885 | DOI Listing |
Hum Immunol
November 2024
Department of Immunology, Duke University School of Medicine, Durham, NC, USA; Department of Surgery, Duke University School of Medicine, Durham, NC, USA. Electronic address:
Clin Transplant
January 2024
Cedars-Sinai Heart Institute, Los Angeles, California, USA.
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 PDFTransplant Cell Ther
August 2023
Bone Marrow Transplantation Unit - Complexo Hospital de Clínicas, Federal University of Paraná, Curitiba, PR, Brazil.
Graft failure (GF) is one of the major concerns after allogeneic hematopoietic cell transplantation (allo-HCT) and remains a significant cause of morbidity and mortality. Although previous reports have associated the presence of donor-specific HLA antibodies (DSAs) with an increased risk of GF after unrelated donor allo-HCT, recent studies have failed to confirm this association. We sought to validate the presence of DSAs as a risk factor for GF and hematologic recovery in the unrelated donor allo-HCT setting.
View Article and Find Full Text PDFJ 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.
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