Association of Circulating Anti-HLA Donor-Specific Antibodies and Their Characteristics, including C1q-Binding Capacity, in Kidney Transplant Recipients with Long-Term Renal Graft Outcomes

Abstract

Post-transplant antihuman leukocyte antigen donor-specific antibodies (anti-HLA DSAs) monitoring in kidney transplant recipients remains unclear and is currently under investigation. The pathogenicity of anti-HLA DSAs is determined by antibody classes, specificity, mean fluorescent intensity (MFI), C1q-binding capacity, and IgG subclasses. The aim of this study was to investigate the association of circulating DSAs and their characteristics with renal allograft long-term outcomes. The study included 108 consecutive patients from our transplant center who underwent kidney allograft biopsy between November 2018 and November 2020, 3 to 24 months after kidney transplantation. At the time of biopsy, patients’ sera were collected for analysis of anti-HLA DSAs. Patients were followed for a median time of 39.0 months (Q1–Q3, 29.8–45.0). Detection of anti-HLA DSAs at the time of biopsy (HR = 5.133, 95% CI 2.150–12.253, p = 0.0002) and their C1q-binding capacity (HR = 14.639, 95% CI 5.320–40.283, p ≤ 0.0001) were independent predictors of the composite of sustained 30% reduction from estimated glomerular filtration rate or death-censored graft failure. Identification of anti-HLA DSAs and their C1q-binding capacity could be useful in identifying kidney transplant recipients at risk for inferior renal allograft function and graft failure. Analysis of C1q is noninvasive, accessible, and should be considered in clinical practice in post-transplant monitoring.

Clinical Outcome of Kidney Transplant Recipients with C1q-Binding De Novo Donor Specific Antibodies: A Single-Center Experience

“…Most clinical studies have investigated the role of pre-existing C1q-binding DSA in kidney transplantation [ 49 , 56 , 57 ]. Notably, different aspects of clinical utility of C1q-binding DSA were found in pre- and post-transplant settings.…”

Impact of Resolved Preformed, Persistent Preformed, and De Novo Anti-HLA Donor-Specific Antibodies in Kidney Transplant Recipients on Long-Term Renal Graft Outcomes

“…This is a post hoc analysis of the study conducted in our transplant center [19]. All 108 consecutive kidney transplant recipients from brain-dead deceased donors from the mentioned study were included in this retrospective study.…”

“…At the time of biopsy, serum samples were obtained from all the patients and stored for further analysis. Sera were tested for the presence of anti-HLA DSAs and their characteristics including class, specificity, MFI, C1q-binding capacity, and IgG subclass according to the protocol described previously [19]. Clinical and laboratory data including the DSA status of the patients before KTx were retrospectively extracted from the medical records.…”