Correlations between donor-specific antibodies and non-adherence with chronic active antibody-mediated rejection phenotypes and their impact on kidney graft survival

Hum Immunol. 2018 Jun;79(6):413-423. doi: 10.1016/j.humimm.2018.03.004. Epub 2018 Mar 22.

Abstract

Chronic-active antibody-mediated rejection (CAABMR) is associated with poor kidney graft survival and has no clear effective treatment. Forty-one cases of CAABMR were detected in indication graft biopsies and evaluated according to current Banff classification. We investigated the impact of concurrent donor-specific antibodies (DSA) and their characteristics, together with non-adherence regarding immunosuppression on CAABMR histopathological phenotypes and prognosis. Twenty-four (59%) patients had detectable DSA at biopsy, with 15 of them being considered non-adherent. Graft function at biopsy was similar in DSA (+) and (-) patients. DSA (+) patients had significantly higher tubulointerstitial inflammation (i and ti) and acute humoral (g+ptc+v+C4d) composite score than DSA (-). DSA (+)/non-adherent cases presented additionally with increased microvascular inflammation (ptc and v), besides having a distinctively lower ah score. C1q DSA strength was higher (P = .046) in non-adherent patients and correlated closely with C4d score (P = .002). Lower graft function and ah score, higher proteinuria and ci + ct score, and, separately per each model, DSA (+) (HR = 2.446, P = .034), DSA (+)/non-adherent (HR = 3.657, P = .005) and DSA (+)/C1q (+) (HR = 4.831, P = .003) status were independent predictors of graft failure. CAABMR with concomitant DSA pose a higher risk of graft failure. Adherence should be evaluated, and histopathological phenotyping and DSA characterization may add critical information.

Keywords: Chronic active antibody-mediated rejection; Donor-specific antibodies; Kidney transplantation; Transplant glomerulopathy; Treatment.

MeSH terms

  • Adult
  • Chronic Disease
  • Cohort Studies
  • Complement C1q / metabolism
  • Female
  • Graft Rejection / epidemiology
  • Graft Rejection / immunology*
  • Graft Rejection / prevention & control
  • Graft Survival
  • Humans
  • Immunity, Humoral
  • Immunosuppressive Agents / therapeutic use
  • Isoantibodies / metabolism*
  • Kidney Transplantation*
  • Male
  • Medication Adherence / statistics & numerical data
  • Middle Aged
  • Phenotype
  • Tissue Donors

Substances

  • Immunosuppressive Agents
  • Isoantibodies
  • Complement C1q