Diffuse Extent of Peritubular Capillaritis in Late Antibody-Mediated Rejection: Associations With Levels of Donor-Specific Antibodies and Chronic Allograft Injury

Transplantation. 2017 May;101(5):e178-e187. doi: 10.1097/TP.0000000000001707.

Abstract

Background: Recently, diffuse peritubular capillaritis (ptc) has been suggested to independently predict chronic transplant injury and loss, and although the ptc score is a diagnostic criterion for antibody-mediated rejection, the utility of diffuse ptc is under debate.

Methods: We evaluated the diagnostic value of ptc characteristics in this cross-sectional study including 85 biopsies of patients with donor-specific antibodies (DSA). Biopsies were reevaluated for the extent (diffuse vs focal), score and leukocytic composition in relation to DSA binding strength (mean fluorescence intensity [MFI]_max). Chronic allograft injury (transplant chronic glomerulopathy [cg] or chronic lesion score CLS]) were associated with ptc features.

Results: Peritubular capillaritis was detected in 50% (76% mononuclear ptc). Peritubular capillaritis scores 1, 2, and 3 were present in 36%, 55%, and 9%, and focal or diffuse ptc in 36% or 64%. Diffuse ptc was associated with DSA MFI_max (median: 4407 vs 2419 [focal ptc; P = 0.04] or 1946 [no ptc; P = 0.004]), cg (58% vs no ptc 24% [P = 0.02]), and higher CLS (mean: 6.81 vs 4.67 [focal ptc, P = 0.01] or 5.18 [no ptc, P = 0.001]), respectively. The association of ptc score of 2 or greater with cg was slightly better than with diffuse ptc. Diffuse ptc and ptc score of 2 or greater remained independently related to cg after adjusting for DSA_MFI_max, C4d, or previous rejection episodes, however lost their independent relation after adjusting for total microcirculation scores. Diffuse ptc was the only ptc characteristic independently related to CLS.

Conclusions: Our results emphasize the clinical relevance of reporting diffuse ptc, which may relate to DSA binding strength and potentially to chronic graft injury.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers / metabolism
  • Biopsy
  • Capillaries / immunology
  • Capillaries / pathology*
  • Cross-Sectional Studies
  • Female
  • Graft Rejection / immunology*
  • Graft Rejection / pathology
  • HLA Antigens / immunology*
  • Humans
  • Isoantibodies / metabolism*
  • Kidney Transplantation*
  • Kidney Tubules / blood supply
  • Kidney Tubules / immunology
  • Kidney Tubules / pathology*
  • Male
  • Middle Aged
  • Vasculitis / immunology*
  • Vasculitis / pathology

Substances

  • Biomarkers
  • HLA Antigens
  • Isoantibodies