Immunohistochemical markers of tissue injury in biopsies with transplant glomerulitis

Ibrahim Batal, Jamil Azzi, Najib El-Haddad, Leonardo V. Riella, John G. Lunz, Adriana Zeevi, Eizaburo Sasatomi, Amit Basu, Henkie Tan, Ron Shapiro, Parmjeet Randhawa

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Transplant glomerulitis is associated with suboptimal graft function. To understand its pathogenesis and to assess the parameters of potential prognostic value, we immunostained 25 paraffin-embedded allograft biopsies showing glomerulitis for markers of complement activation (C4d), cytotoxicity (Granzyme-B), apoptosis (Bcl-XL, Bcl-2, and Fas-L), and endothelial injury (von Willebrand factor). Staining was semiquantitatively assessed in different anatomical compartments, and comparison was made with 40 control allograft biopsies without glomerulitis. Biopsies with glomerulitis had more frequent incidence of "mixed" T-cell and antibody-mediated rejection compared with controls [8/25 (32%) versus 4/40 (10%), P =.046]. Furthermore, they had higher glomerular capillary-C4d scores (1.9 ± 1.1 versus 1.2 ± 1.2, P =.015), which tended to persist when biopsies showing transplant glomerulopathy were excluded. Higher glomerular capillary-C4d scores were observed in samples with versus without donor-specific antibody (2.5 ± 0.9 versus 1.2 ± 1.2, P =.01). Compared with controls, biopsies with glomerulitis had more intraglomerular (4.8 ± 4.5 versus 0.9± 0.8 cells/glomerulus, P <.001) and interstitial mainly peritubular capillary (6.1 ± 4.1 versus 3.2 ± 3.4 cells/hpf, P =.002) Granzyme-B + leukocytes. Higher mesangial-von Willebrand factor scores were noted in the glomerulitis group (1.8 ± 1.0 versus 0.8 ± 0.8, P =.003) and correlated with the percentage of inflamed glomeruli (r = 0.54, P <.001). Interstitial-von Willebrand factor was associated with a higher peritubular capillaritis score (interstitial-von Willebrand factor: 1.6 ± 1.2 versus no interstitial-von Willebrand factor: 0.6 ± 0.9, P =.02). Glomerular capillary-Bcl-XL was not associated with accommodation. Finally, no difference in Bcl-2 or Fas-L was observed upon comparing glomerulitis to controls. In conclusion, glomerular injury in transplant glomerulitis appears to be mediated by complement activation and cellular cytotoxicity. Mesangial- or interstitial-von Willebrand factor identified cases with more severe microcirculation injury.

Original languageEnglish (US)
Pages (from-to)69-80
Number of pages12
JournalHuman Pathology
Volume43
Issue number1
DOIs
StatePublished - Jan 2012
Externally publishedYes

Keywords

  • Complement activation
  • Cytotoxicity
  • Microcirculation injury
  • Transplant glomerulitis

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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