C1q-binding DSA and allograft outcomes in pediatric kidney transplant recipients

Pediatr Transplant. 2021 Mar;25(2):e13885. doi: 10.1111/petr.13885. Epub 2020 Nov 1.

Abstract

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.

Keywords: allograft function; antibodies; antibody mediated rejection.

MeSH terms

  • Adolescent
  • Allografts / immunology*
  • Biomarkers / blood
  • Child
  • Child, Preschool
  • Complement C1q / immunology*
  • Female
  • Follow-Up Studies
  • Graft Rejection / blood
  • Graft Rejection / diagnosis
  • Graft Rejection / immunology*
  • Graft Survival / immunology*
  • HLA Antigens / blood
  • HLA Antigens / immunology*
  • Humans
  • Isoantibodies / blood
  • Isoantibodies / immunology*
  • Kaplan-Meier Estimate
  • Kidney Transplantation*
  • Logistic Models
  • Male
  • Outcome Assessment, Health Care
  • Retrospective Studies
  • Risk Assessment
  • Risk Factors
  • Tissue Donors

Substances

  • Biomarkers
  • HLA Antigens
  • Isoantibodies
  • Complement C1q