TY - JOUR
T1 - Immunohistochemical markers of tissue injury in biopsies with transplant glomerulitis
AU - Batal, Ibrahim
AU - Azzi, Jamil
AU - El-Haddad, Najib
AU - Riella, Leonardo V.
AU - Lunz, John G.
AU - Zeevi, Adriana
AU - Sasatomi, Eizaburo
AU - Basu, Amit
AU - Tan, Henkie
AU - Shapiro, Ron
AU - Randhawa, Parmjeet
N1 - Funding Information:
Supported by Research Fellowship Grant from the College of American Pathologists Foundation, Chicago, IL (IB).
PY - 2012/1
Y1 - 2012/1
N2 - 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.
AB - 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.
KW - Complement activation
KW - Cytotoxicity
KW - Microcirculation injury
KW - Transplant glomerulitis
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U2 - 10.1016/j.humpath.2011.04.008
DO - 10.1016/j.humpath.2011.04.008
M3 - Article
C2 - 21777946
AN - SCOPUS:83055173025
SN - 0046-8177
VL - 43
SP - 69
EP - 80
JO - Human Pathology
JF - Human Pathology
IS - 1
ER -