Role of morphologic parameters on endomyocardial biopsy to detect sub-clinical antibody-mediated rejection in heart transplantation

Marny Fedrigo, Antonio Gambino, Elena Benazzi, Francesca Poli, Anna Chiara Frigo, Francesco Tona, Alida L P Caforio, Chiara Castellani, Giuseppe Toscano, Giuseppe Feltrin, Gino Gerosa, Gaetano Thiene, Annalisa Angelini

Research output: Contribution to journalArticle

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Abstract

Background: The present study evaluated if morphologic parameters detect signs of early sub-clinical or latent stages of antibody-mediated rejection (AMR) and their correlation with C4d staining in cardiac transplants recipients. Methods: The study reviewed 1,270 endomyocardial biopsies (EMB) from 131 patients. Of these, 61 stained positive for C4d in the absence of acute cellular rejection >2R. Sixty-six EMB specimens negative for C4d were matched for pre-transplant diagnosis, time after transplantation, age, and acute cellular rejection (ACR) grading. Histopathologic evaluation and C4d staining were performed on formalin-fixed, paraffin-embedded sections using the C4d polyclonal antibody. Results: Of the 8 histologic characteristics evaluated, only endothelial swelling (78.7% sensitivity, 28.8% specificity; positive likelihood ratio, 1.10) and interstitial edema (77% sensitivity, 31.8% specificity; positive likelihood ratio, 1.13) could be considered fair predictors of C4d capillary positivity. The presence of mononuclear cells in capillaries in relation to C4d positivity showed 39.3% sensitivity and 68.2% specificity. Combining the parameters endothelial swelling and mononuclear cells in capillaries, sensitivity was 31.1% (95% confidence interval [CI] 19.944.3) and specificity was 71.2% (95 CI, 58.881.7), with a positive likelihood ratio of 1.08 (95% CI, 0.681.84). Conclusions: Our results showed that histologic parameters did not always detect signs of early sub-clinical or latent stages of AMR. Combining the parameters of endothelial swelling and intracapillary mononuclear cells did not significantly improve the sensitivity or specificity. Screening recommendations should, therefore, be modified to include more sensitive tests such as C4d staining in the routine protocol to improve patient risk stratification.

Original languageEnglish
Pages (from-to)1381-1388
Number of pages8
JournalJournal of Heart and Lung Transplantation
Volume30
Issue number12
DOIs
Publication statusPublished - Dec 2011

Fingerprint

Heart Transplantation
Biopsy
Sensitivity and Specificity
Antibodies
Confidence Intervals
Staining and Labeling
Paraffin
Formaldehyde
Edema
Transplantation
Transplants

Keywords

  • Antibody-mediated rejection
  • C4d
  • heart transplantation
  • immunohistochemistry
  • morphology

ASJC Scopus subject areas

  • Transplantation
  • Cardiology and Cardiovascular Medicine
  • Pulmonary and Respiratory Medicine
  • Surgery

Cite this

Role of morphologic parameters on endomyocardial biopsy to detect sub-clinical antibody-mediated rejection in heart transplantation. / Fedrigo, Marny; Gambino, Antonio; Benazzi, Elena; Poli, Francesca; Frigo, Anna Chiara; Tona, Francesco; Caforio, Alida L P; Castellani, Chiara; Toscano, Giuseppe; Feltrin, Giuseppe; Gerosa, Gino; Thiene, Gaetano; Angelini, Annalisa.

In: Journal of Heart and Lung Transplantation, Vol. 30, No. 12, 12.2011, p. 1381-1388.

Research output: Contribution to journalArticle

Fedrigo, M, Gambino, A, Benazzi, E, Poli, F, Frigo, AC, Tona, F, Caforio, ALP, Castellani, C, Toscano, G, Feltrin, G, Gerosa, G, Thiene, G & Angelini, A 2011, 'Role of morphologic parameters on endomyocardial biopsy to detect sub-clinical antibody-mediated rejection in heart transplantation', Journal of Heart and Lung Transplantation, vol. 30, no. 12, pp. 1381-1388. https://doi.org/10.1016/j.healun.2011.07.012
Fedrigo, Marny ; Gambino, Antonio ; Benazzi, Elena ; Poli, Francesca ; Frigo, Anna Chiara ; Tona, Francesco ; Caforio, Alida L P ; Castellani, Chiara ; Toscano, Giuseppe ; Feltrin, Giuseppe ; Gerosa, Gino ; Thiene, Gaetano ; Angelini, Annalisa. / Role of morphologic parameters on endomyocardial biopsy to detect sub-clinical antibody-mediated rejection in heart transplantation. In: Journal of Heart and Lung Transplantation. 2011 ; Vol. 30, No. 12. pp. 1381-1388.
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abstract = "Background: The present study evaluated if morphologic parameters detect signs of early sub-clinical or latent stages of antibody-mediated rejection (AMR) and their correlation with C4d staining in cardiac transplants recipients. Methods: The study reviewed 1,270 endomyocardial biopsies (EMB) from 131 patients. Of these, 61 stained positive for C4d in the absence of acute cellular rejection >2R. Sixty-six EMB specimens negative for C4d were matched for pre-transplant diagnosis, time after transplantation, age, and acute cellular rejection (ACR) grading. Histopathologic evaluation and C4d staining were performed on formalin-fixed, paraffin-embedded sections using the C4d polyclonal antibody. Results: Of the 8 histologic characteristics evaluated, only endothelial swelling (78.7{\%} sensitivity, 28.8{\%} specificity; positive likelihood ratio, 1.10) and interstitial edema (77{\%} sensitivity, 31.8{\%} specificity; positive likelihood ratio, 1.13) could be considered fair predictors of C4d capillary positivity. The presence of mononuclear cells in capillaries in relation to C4d positivity showed 39.3{\%} sensitivity and 68.2{\%} specificity. Combining the parameters endothelial swelling and mononuclear cells in capillaries, sensitivity was 31.1{\%} (95{\%} confidence interval [CI] 19.944.3) and specificity was 71.2{\%} (95 CI, 58.881.7), with a positive likelihood ratio of 1.08 (95{\%} CI, 0.681.84). Conclusions: Our results showed that histologic parameters did not always detect signs of early sub-clinical or latent stages of AMR. Combining the parameters of endothelial swelling and intracapillary mononuclear cells did not significantly improve the sensitivity or specificity. Screening recommendations should, therefore, be modified to include more sensitive tests such as C4d staining in the routine protocol to improve patient risk stratification.",
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AU - Poli, Francesca

AU - Frigo, Anna Chiara

AU - Tona, Francesco

AU - Caforio, Alida L P

AU - Castellani, Chiara

AU - Toscano, Giuseppe

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