Potential of real-time PCR assessment of granzyme B and perforin up-regulation for rejection monitoring in intestinal transplant recipients

B. Corti, A. Altimari, E. Gabusi, A. D. Pinna, A. Lauro, A. M. Morselli-Labate, E. Gruppioni, M. G. Pirini, M. Fiorentino, L. Ridolfi, W. F. Grigioni, A. D'Errico-Grigioni

Research output: Contribution to journalArticle

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Abstract

Granzyme B (GrB) and perforin are promising markers to predict acute rejection episodes of transplanted organs. Having recently reported that immunohistochemical expression of GrB/perforin correlates with histologically assessed acute cellular rejection (ACR) episodes in intestinal transplantation recipients, herein we have additionally explored the potential of real-time polymerase chain reaction (PCR) assessment of GrB/perforin gene up-regulation in peripheral blood mononuclear cells. Both immunohistochemical evaluation of GrB/perforin expression and real-time PCR assessment of up-regulation, which was defined as a 2-fold increase with respect to "basal" levels during maintenance immunosuppressive protocols, were performed among a population of 23 intestinal transplant recipients under routine surveillance, in addition to histological analysis of ACR. The ACR scores showed direct relationships both with GrB/perforin immunohistochemistry (IHC) scores (P <.001) and with gene up-regulation by real-time PCR (P = .004). Furthermore, real-time PCR upregulation was associated with the IHC score (P <.001). A preliminary analysis of diagnostic accuracy-performed to gain information to plan future studies-indicated that when using histological assessment as the reference technique, our current definition of PCR up-regulation provided good specificity (84%) but insufficient sensitivity (44%) for a noninvasive prediction of ACR. The results of this pilot study suggested that real-time PCR analysis of GrB/perforin upregulation may help therapeutic decision making, and have the potential for detection of presymptomatic rejection. More extensive studies must investigate strategies to improve the sensitivity of the analyses of GrB/perforin up-regulation.

Original languageEnglish
Pages (from-to)4467-4471
Number of pages5
JournalTransplantation Proceedings
Volume37
Issue number10
DOIs
Publication statusPublished - Dec 2005

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Real-Time Polymerase Chain Reaction
Up-Regulation
Immunohistochemistry
Immunosuppressive Agents
Rejection (Psychology)
perforin-granzyme B
Transplant Recipients
Genes
Blood Cells
Decision Making
Transplantation
Maintenance
Polymerase Chain Reaction
Population

ASJC Scopus subject areas

  • Surgery
  • Transplantation

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Potential of real-time PCR assessment of granzyme B and perforin up-regulation for rejection monitoring in intestinal transplant recipients. / Corti, B.; Altimari, A.; Gabusi, E.; Pinna, A. D.; Lauro, A.; Morselli-Labate, A. M.; Gruppioni, E.; Pirini, M. G.; Fiorentino, M.; Ridolfi, L.; Grigioni, W. F.; D'Errico-Grigioni, A.

In: Transplantation Proceedings, Vol. 37, No. 10, 12.2005, p. 4467-4471.

Research output: Contribution to journalArticle

Corti, B, Altimari, A, Gabusi, E, Pinna, AD, Lauro, A, Morselli-Labate, AM, Gruppioni, E, Pirini, MG, Fiorentino, M, Ridolfi, L, Grigioni, WF & D'Errico-Grigioni, A 2005, 'Potential of real-time PCR assessment of granzyme B and perforin up-regulation for rejection monitoring in intestinal transplant recipients', Transplantation Proceedings, vol. 37, no. 10, pp. 4467-4471. https://doi.org/10.1016/j.transproceed.2005.11.035
Corti, B. ; Altimari, A. ; Gabusi, E. ; Pinna, A. D. ; Lauro, A. ; Morselli-Labate, A. M. ; Gruppioni, E. ; Pirini, M. G. ; Fiorentino, M. ; Ridolfi, L. ; Grigioni, W. F. ; D'Errico-Grigioni, A. / Potential of real-time PCR assessment of granzyme B and perforin up-regulation for rejection monitoring in intestinal transplant recipients. In: Transplantation Proceedings. 2005 ; Vol. 37, No. 10. pp. 4467-4471.
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AU - Altimari, A.

AU - Gabusi, E.

AU - Pinna, A. D.

AU - Lauro, A.

AU - Morselli-Labate, A. M.

AU - Gruppioni, E.

AU - Pirini, M. G.

AU - Fiorentino, M.

AU - Ridolfi, L.

AU - Grigioni, W. F.

AU - D'Errico-Grigioni, A.

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AB - Granzyme B (GrB) and perforin are promising markers to predict acute rejection episodes of transplanted organs. Having recently reported that immunohistochemical expression of GrB/perforin correlates with histologically assessed acute cellular rejection (ACR) episodes in intestinal transplantation recipients, herein we have additionally explored the potential of real-time polymerase chain reaction (PCR) assessment of GrB/perforin gene up-regulation in peripheral blood mononuclear cells. Both immunohistochemical evaluation of GrB/perforin expression and real-time PCR assessment of up-regulation, which was defined as a 2-fold increase with respect to "basal" levels during maintenance immunosuppressive protocols, were performed among a population of 23 intestinal transplant recipients under routine surveillance, in addition to histological analysis of ACR. The ACR scores showed direct relationships both with GrB/perforin immunohistochemistry (IHC) scores (P <.001) and with gene up-regulation by real-time PCR (P = .004). Furthermore, real-time PCR upregulation was associated with the IHC score (P <.001). A preliminary analysis of diagnostic accuracy-performed to gain information to plan future studies-indicated that when using histological assessment as the reference technique, our current definition of PCR up-regulation provided good specificity (84%) but insufficient sensitivity (44%) for a noninvasive prediction of ACR. The results of this pilot study suggested that real-time PCR analysis of GrB/perforin upregulation may help therapeutic decision making, and have the potential for detection of presymptomatic rejection. More extensive studies must investigate strategies to improve the sensitivity of the analyses of GrB/perforin up-regulation.

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