Two Years’ Experience of Acute Rejection Monitoring of Intestinal Transplant Recipients by Real-Time PCR Assessment of Granzyme B and Perforin Up-Regulation: Considerations on Diagnostic Accuracy
Granzyme B (GrB) and perforin are promising immunological markers to predict acute rejection of transplanted organs. Based on 2 years of experience with molecular monitoring on peripheral blood samples, we investigated the diagnostic accuracy of GrB/perforin gene up-regulation using real-time polyme...
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creator | Corti, B. Altimari, A. Gabusi, E. Pinna, A.D. Gruppioni, E. Lauro, A. Pirini, M.G. Fiorentino, M. Ridolfi, L. Grigioni, W.F. Grigioni, A.D. |
description | Granzyme B (GrB) and perforin are promising immunological markers to predict acute rejection of transplanted organs. Based on 2 years of experience with molecular monitoring on peripheral blood samples, we investigated the diagnostic accuracy of GrB/perforin gene up-regulation using real-time polymerase chain reaction (PCR) for prediction of acute cellular rejection (ACR) in intestinal transplantation recipients. Histology used as the reference standard. According to our definition of disease positivity (anything other than ACR score 0), GrB/perforin up-regulation showed 84% specificity but only 49% sensitivity. However, among the 26 false-negatives, 12 (46%) had an ACR score 1, which is indeterminate for rejection and no associated clinical manifestations; a further 10 (39%) had a score of 2 following rejection therapy (a confounder for GrB/perforin analysis). Thus only 4 (15%) false-negatives were actually associated with the onset of robust acute rejection. These data suggest that real-time PCR analysis for GrB/perforin up-regulation might play a role along with clinical criteria for detection of presymptomatic acute rejection episodes in intestinal recipients who require immediate endoscopy and pathological examination, especially during long-term follow-up. |
doi_str_mv | 10.1016/j.transproceed.2006.05.013 |
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Based on 2 years of experience with molecular monitoring on peripheral blood samples, we investigated the diagnostic accuracy of GrB/perforin gene up-regulation using real-time polymerase chain reaction (PCR) for prediction of acute cellular rejection (ACR) in intestinal transplantation recipients. Histology used as the reference standard. According to our definition of disease positivity (anything other than ACR score 0), GrB/perforin up-regulation showed 84% specificity but only 49% sensitivity. However, among the 26 false-negatives, 12 (46%) had an ACR score 1, which is indeterminate for rejection and no associated clinical manifestations; a further 10 (39%) had a score of 2 following rejection therapy (a confounder for GrB/perforin analysis). Thus only 4 (15%) false-negatives were actually associated with the onset of robust acute rejection. These data suggest that real-time PCR analysis for GrB/perforin up-regulation might play a role along with clinical criteria for detection of presymptomatic acute rejection episodes in intestinal recipients who require immediate endoscopy and pathological examination, especially during long-term follow-up.</description><identifier>ISSN: 0041-1345</identifier><identifier>EISSN: 1873-2623</identifier><identifier>DOI: 10.1016/j.transproceed.2006.05.013</identifier><identifier>PMID: 16908262</identifier><identifier>CODEN: TRPPA8</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>Biological and medical sciences ; Fundamental and applied biological sciences. Psychology ; Fundamental immunology ; Gene Expression Regulation ; Gene Expression Regulation, Enzymologic ; Graft Rejection - epidemiology ; Graft Rejection - genetics ; Granzymes ; Humans ; Intestines - transplantation ; Medical sciences ; Membrane Glycoproteins - genetics ; Perforin ; Polymerase Chain Reaction - methods ; Pore Forming Cytotoxic Proteins ; Reproducibility of Results ; Serine Endopeptidases - genetics ; Surgery (general aspects). Transplantations, organ and tissue grafts. 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Based on 2 years of experience with molecular monitoring on peripheral blood samples, we investigated the diagnostic accuracy of GrB/perforin gene up-regulation using real-time polymerase chain reaction (PCR) for prediction of acute cellular rejection (ACR) in intestinal transplantation recipients. Histology used as the reference standard. According to our definition of disease positivity (anything other than ACR score 0), GrB/perforin up-regulation showed 84% specificity but only 49% sensitivity. However, among the 26 false-negatives, 12 (46%) had an ACR score 1, which is indeterminate for rejection and no associated clinical manifestations; a further 10 (39%) had a score of 2 following rejection therapy (a confounder for GrB/perforin analysis). Thus only 4 (15%) false-negatives were actually associated with the onset of robust acute rejection. These data suggest that real-time PCR analysis for GrB/perforin up-regulation might play a role along with clinical criteria for detection of presymptomatic acute rejection episodes in intestinal recipients who require immediate endoscopy and pathological examination, especially during long-term follow-up.</description><subject>Biological and medical sciences</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Fundamental immunology</subject><subject>Gene Expression Regulation</subject><subject>Gene Expression Regulation, Enzymologic</subject><subject>Graft Rejection - epidemiology</subject><subject>Graft Rejection - genetics</subject><subject>Granzymes</subject><subject>Humans</subject><subject>Intestines - transplantation</subject><subject>Medical sciences</subject><subject>Membrane Glycoproteins - genetics</subject><subject>Perforin</subject><subject>Polymerase Chain Reaction - methods</subject><subject>Pore Forming Cytotoxic Proteins</subject><subject>Reproducibility of Results</subject><subject>Serine Endopeptidases - genetics</subject><subject>Surgery (general aspects). Transplantations, organ and tissue grafts. 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Psychology</topic><topic>Fundamental immunology</topic><topic>Gene Expression Regulation</topic><topic>Gene Expression Regulation, Enzymologic</topic><topic>Graft Rejection - epidemiology</topic><topic>Graft Rejection - genetics</topic><topic>Granzymes</topic><topic>Humans</topic><topic>Intestines - transplantation</topic><topic>Medical sciences</topic><topic>Membrane Glycoproteins - genetics</topic><topic>Perforin</topic><topic>Polymerase Chain Reaction - methods</topic><topic>Pore Forming Cytotoxic Proteins</topic><topic>Reproducibility of Results</topic><topic>Serine Endopeptidases - genetics</topic><topic>Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases</topic><topic>Tissue, organ and graft immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Corti, B.</creatorcontrib><creatorcontrib>Altimari, A.</creatorcontrib><creatorcontrib>Gabusi, E.</creatorcontrib><creatorcontrib>Pinna, A.D.</creatorcontrib><creatorcontrib>Gruppioni, E.</creatorcontrib><creatorcontrib>Lauro, A.</creatorcontrib><creatorcontrib>Pirini, M.G.</creatorcontrib><creatorcontrib>Fiorentino, M.</creatorcontrib><creatorcontrib>Ridolfi, L.</creatorcontrib><creatorcontrib>Grigioni, W.F.</creatorcontrib><creatorcontrib>Grigioni, A.D.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Transplantation proceedings</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Corti, B.</au><au>Altimari, A.</au><au>Gabusi, E.</au><au>Pinna, A.D.</au><au>Gruppioni, E.</au><au>Lauro, A.</au><au>Pirini, M.G.</au><au>Fiorentino, M.</au><au>Ridolfi, L.</au><au>Grigioni, W.F.</au><au>Grigioni, A.D.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Two Years’ Experience of Acute Rejection Monitoring of Intestinal Transplant Recipients by Real-Time PCR Assessment of Granzyme B and Perforin Up-Regulation: Considerations on Diagnostic Accuracy</atitle><jtitle>Transplantation proceedings</jtitle><addtitle>Transplant Proc</addtitle><date>2006-07-01</date><risdate>2006</risdate><volume>38</volume><issue>6</issue><spage>1726</spage><epage>1727</epage><pages>1726-1727</pages><issn>0041-1345</issn><eissn>1873-2623</eissn><coden>TRPPA8</coden><abstract>Granzyme B (GrB) and perforin are promising immunological markers to predict acute rejection of transplanted organs. Based on 2 years of experience with molecular monitoring on peripheral blood samples, we investigated the diagnostic accuracy of GrB/perforin gene up-regulation using real-time polymerase chain reaction (PCR) for prediction of acute cellular rejection (ACR) in intestinal transplantation recipients. Histology used as the reference standard. According to our definition of disease positivity (anything other than ACR score 0), GrB/perforin up-regulation showed 84% specificity but only 49% sensitivity. However, among the 26 false-negatives, 12 (46%) had an ACR score 1, which is indeterminate for rejection and no associated clinical manifestations; a further 10 (39%) had a score of 2 following rejection therapy (a confounder for GrB/perforin analysis). Thus only 4 (15%) false-negatives were actually associated with the onset of robust acute rejection. These data suggest that real-time PCR analysis for GrB/perforin up-regulation might play a role along with clinical criteria for detection of presymptomatic acute rejection episodes in intestinal recipients who require immediate endoscopy and pathological examination, especially during long-term follow-up.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>16908262</pmid><doi>10.1016/j.transproceed.2006.05.013</doi><tpages>2</tpages></addata></record> |
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subjects | Biological and medical sciences Fundamental and applied biological sciences. Psychology Fundamental immunology Gene Expression Regulation Gene Expression Regulation, Enzymologic Graft Rejection - epidemiology Graft Rejection - genetics Granzymes Humans Intestines - transplantation Medical sciences Membrane Glycoproteins - genetics Perforin Polymerase Chain Reaction - methods Pore Forming Cytotoxic Proteins Reproducibility of Results Serine Endopeptidases - genetics Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases Tissue, organ and graft immunology |
title | Two Years’ Experience of Acute Rejection Monitoring of Intestinal Transplant Recipients by Real-Time PCR Assessment of Granzyme B and Perforin Up-Regulation: Considerations on Diagnostic Accuracy |
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