Comparing transplant glomerulopathy in the absence of C4d deposition and donor-specific antibodies to chronic antibody-mediated rejection

Clin Transplant. 2014 Oct;28(10):1148-54. doi: 10.1111/ctr.12433. Epub 2014 Sep 11.

Abstract

Introduction: Transplant glomerulopathy (TG) is the characteristic lesion of chronic antibody-mediated rejection (AMR). However, in some patients presents with no circulating HLA antibodies or C4d positivity.

Aim: Patients with TG accomplishing criteria for chronic AMR were compared to patients with isolated TG.

Patients and methods: We reviewed late (>6 months) graft biopsies performed between 2007 and 2010 (n = 75). Biopsies with C4d-negative TG and no circulating donor-specific antibody were called isolated TG (n = 12), and chronic AMR was defined according to Banff consensus (n = 17). HLA antibodies were evaluated by Luminex technology. Immunohistochemistry was performed to quantify graft infiltrating cells.

Results: Patients with isolated TG were older (52 ± 14 vs. 35 ± 14; p = 0.0048), received grafts from older donors (54 ± 16 vs. 41 ± 18; p = 0.0554), and displayed a lower inflammation in the glomerular (g-score: 0.5 ± 0.5 vs. 1.0 ± 0.9; p = 0.0865; CD3 positive cells/glomeruli: 1.5 ± 2.9 vs. 4.4 ± 4.1; p = 0.0147), interstitial (i-score: 1.2 ± 0.9 vs. 1.9 ± 1.0; p = 0.0685; CD45 positive cells/hpf: 18 ± 11 vs. 57 ± 68; p = 0.0132), and peritubular capillary (ptc-score 0.2 ± 0.6 vs. 1.1 ± 0.9; p = 0.0089; CD45 positive cells/hpf: 3.7 ± 3.1 vs. 10.1 ± 7.4; p = 0.0290) compartments. Fifteen grafts were lost and graft survival was significantly lower in patients with chronic AMR (p = 0.0122).

Conclusion: Isolated TG is associated with less severe allograft inflammation and with a better outcome than chronic AMR.

Keywords: chronic antibody-mediated rejection; donor-specific antibodies; transplant glomerulopathy.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Chronic Disease / mortality*
  • Complement C4b / immunology*
  • Female
  • Fluorescent Antibody Technique
  • Follow-Up Studies
  • Glomerular Filtration Rate
  • Glomerulonephritis / immunology*
  • Graft Rejection / immunology*
  • Graft Rejection / mortality
  • Graft Rejection / pathology
  • Graft Survival
  • Humans
  • Immunoenzyme Techniques
  • Isoantibodies / immunology*
  • Kidney Failure, Chronic / immunology*
  • Kidney Failure, Chronic / mortality
  • Kidney Failure, Chronic / surgery
  • Kidney Function Tests
  • Kidney Transplantation*
  • Male
  • Middle Aged
  • Peptide Fragments / immunology*
  • Prognosis
  • Risk Factors
  • Survival Rate
  • Tissue Donors
  • Transplantation, Homologous

Substances

  • Isoantibodies
  • Peptide Fragments
  • Complement C4b
  • complement C4d