Donor-specific antibodies require preactivated immune system to harm renal transplant

EBioMedicine. 2016 Jul:9:366-371. doi: 10.1016/j.ebiom.2016.06.006. Epub 2016 Jun 5.

Abstract

Background: It is an unresolved issue why some kidney transplant recipients with pretransplant donor-specific HLA antibodies (DSA) show a high transplant failure rate, whereas in other patients DSA do not harm the graft. We investigated whether help from preactivated T-cells might be necessary for DSA to exert a deleterious effect.

Methods: The impact of pretransplant DSA and immune activation marker soluble CD30 (sCD30) on 3-year graft survival was analyzed in 385 presensitized kidney transplant recipients.

Findings: A deleterious influence of pretransplant DSA on graft survival was evident only in patients who were positive for the immune activation marker sCD30. In the absence of sCD30 positivity, 3-year graft survival was virtually identical in patients with or without DSA (83.1±3.9% and 84.3±2.8%, P=0.81). A strikingly lower 3-year graft survival rate of 62.1±6.4% was observed in patients who were both sCD30 and DSA positive (HR 2.92, P<0.001). Even in the presence of strong DSA with ≥5000 MFI, the 3-year graft survival rate was high if the recipients were sCD30 negative.

Interpretation: Pretransplant DSA have a significantly deleterious impact on graft survival only in the presence of high pretransplant levels of the activation marker sCD30.

Keywords: Donor-specific antibodies; Graft outcome; HLA antibodies; Kidney transplantation; Single antigen bead; sCD30.

MeSH terms

  • Adult
  • Aged
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Graft Survival
  • HLA Antigens / blood
  • HLA Antigens / immunology*
  • Humans
  • Immune System / metabolism*
  • Ki-1 Antigen / blood
  • Kidney Failure, Chronic / therapy
  • Kidney Transplantation*
  • Male
  • Middle Aged
  • Proportional Hazards Models
  • Retrospective Studies
  • T-Lymphocytes / cytology
  • T-Lymphocytes / metabolism
  • Tissue Donors

Substances

  • HLA Antigens
  • Ki-1 Antigen