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Virtual Crossmatch in Kidney Transplantation

Abstract Background The Luminex Single-Antigen Beads (LSA) assay allows an accurate detection and characterization of preexisting donor-specific antibodies (DSA) in kidney transplant candidates. But the ability of LSA to detect quite low levels of antibodies makes it hard to correctly predict crossm...

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Published in:Transplantation proceedings 2014-09, Vol.46 (7), p.2195-2198
Main Authors: Piazza, A, Ozzella, G, Poggi, E, Caputo, D, Manfreda, A, Adorno, D
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creator Piazza, A
Ozzella, G
Poggi, E
Caputo, D
Manfreda, A
Adorno, D
description Abstract Background The Luminex Single-Antigen Beads (LSA) assay allows an accurate detection and characterization of preexisting donor-specific antibodies (DSA) in kidney transplant candidates. But the ability of LSA to detect quite low levels of antibodies makes it hard to correctly predict crossmatch results in donor selection. In this study we retrospectively analyzed the accuracy of our virtual crossmatch (v-XM) protocol, which was used for selection of potential kidney transplant recipients, in predicting the results of actual crossmatch (a-XM) in cadaver-donor renal transplantation. We also investigated correlation between negative a-XM results and strength/specificity of preformed DSA. Methods The correlation between negative v-XMs and a-XMs performed in 2007–2012 at the Regional Transplant Center of the Lazio Region, Italy, was analyzed. In carrying out v-XM, the donor HLA molecules against which patients showed LSA-detected DSA with normalized mean fluorescence intensity (MFI) ≥5,000 were considered to be “unacceptable DSA,” and LSA-DSA showing MFI 
doi_str_mv 10.1016/j.transproceed.2014.07.053
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But the ability of LSA to detect quite low levels of antibodies makes it hard to correctly predict crossmatch results in donor selection. In this study we retrospectively analyzed the accuracy of our virtual crossmatch (v-XM) protocol, which was used for selection of potential kidney transplant recipients, in predicting the results of actual crossmatch (a-XM) in cadaver-donor renal transplantation. We also investigated correlation between negative a-XM results and strength/specificity of preformed DSA. Methods The correlation between negative v-XMs and a-XMs performed in 2007–2012 at the Regional Transplant Center of the Lazio Region, Italy, was analyzed. In carrying out v-XM, the donor HLA molecules against which patients showed LSA-detected DSA with normalized mean fluorescence intensity (MFI) ≥5,000 were considered to be “unacceptable DSA,” and LSA-DSA showing MFI &lt;5,000 were defined as “acceptable DSA.” All cadaver donors had been typed for HLA-A, -B, -DR, and -DQB molecules by sequence-specific primer methods. On the basis of a negative v-XM, we performed 507 a-XMs between serum samples from 256 renal transplant candidates and T/B lymphocytes from 302 cadaver donors with the use of both complement-dependent cytotoxicity (CDC) and flow cytometry (FC) methods. Results The v-XM negative results showed good correlation with both CDC and FC a-XMs (97% and 90%, respectively). The sensitivity of v-XM was 100%; this high value was related to the lack of false-negative DSA results. The limited specificity with both techniques (CDC-XM, 74%; FC-XM, 79%) was due to the presence of “acceptable” and/or anti-DQA/DPB DSA in some patient sera used to perform the a-XMs. During the study period, 171 (67%) of the 256 sensitized patients received a kidney transplant: 30% of these had “acceptable DSA” and/or anti-DQA/DPB DSA. No antibody-mediated rejection due to preformed HLA-DSA was observed. Conclusions Our v-XM protocol showed high sensitivity in predicting donor-recipient immunologic compatibility. The results of this study also demonstrated the importance of evaluating DSA strength for implementing v-XM results in the selection of kidney transplant recipients. Moreover, the finding of anti-DQA/DPB DSA, especially in serum samples that gave positive results with the use of both CDC and FC a-XMs, highlights the importance of defining all of the donor HLA molecules to perform an accurate v-XM.</description><identifier>ISSN: 0041-1345</identifier><identifier>EISSN: 1873-2623</identifier><identifier>DOI: 10.1016/j.transproceed.2014.07.053</identifier><identifier>PMID: 25242749</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Antibodies - analysis ; Donor Selection ; Female ; Flow Cytometry ; Histocompatibility Testing - methods ; HLA Antigens - immunology ; Humans ; Italy ; Kidney Transplantation ; Male ; Middle Aged ; Retrospective Studies ; Surgery</subject><ispartof>Transplantation proceedings, 2014-09, Vol.46 (7), p.2195-2198</ispartof><rights>Elsevier Inc.</rights><rights>2014 Elsevier Inc.</rights><rights>Copyright © 2014 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c435t-44108094a04c3d2b32fdb5953cb1bdbc27751e10c0d59d6f0f391b2ecd0d74783</citedby><cites>FETCH-LOGICAL-c435t-44108094a04c3d2b32fdb5953cb1bdbc27751e10c0d59d6f0f391b2ecd0d74783</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25242749$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Piazza, A</creatorcontrib><creatorcontrib>Ozzella, G</creatorcontrib><creatorcontrib>Poggi, E</creatorcontrib><creatorcontrib>Caputo, D</creatorcontrib><creatorcontrib>Manfreda, A</creatorcontrib><creatorcontrib>Adorno, D</creatorcontrib><title>Virtual Crossmatch in Kidney Transplantation</title><title>Transplantation proceedings</title><addtitle>Transplant Proc</addtitle><description>Abstract Background The Luminex Single-Antigen Beads (LSA) assay allows an accurate detection and characterization of preexisting donor-specific antibodies (DSA) in kidney transplant candidates. But the ability of LSA to detect quite low levels of antibodies makes it hard to correctly predict crossmatch results in donor selection. In this study we retrospectively analyzed the accuracy of our virtual crossmatch (v-XM) protocol, which was used for selection of potential kidney transplant recipients, in predicting the results of actual crossmatch (a-XM) in cadaver-donor renal transplantation. We also investigated correlation between negative a-XM results and strength/specificity of preformed DSA. Methods The correlation between negative v-XMs and a-XMs performed in 2007–2012 at the Regional Transplant Center of the Lazio Region, Italy, was analyzed. In carrying out v-XM, the donor HLA molecules against which patients showed LSA-detected DSA with normalized mean fluorescence intensity (MFI) ≥5,000 were considered to be “unacceptable DSA,” and LSA-DSA showing MFI &lt;5,000 were defined as “acceptable DSA.” All cadaver donors had been typed for HLA-A, -B, -DR, and -DQB molecules by sequence-specific primer methods. On the basis of a negative v-XM, we performed 507 a-XMs between serum samples from 256 renal transplant candidates and T/B lymphocytes from 302 cadaver donors with the use of both complement-dependent cytotoxicity (CDC) and flow cytometry (FC) methods. Results The v-XM negative results showed good correlation with both CDC and FC a-XMs (97% and 90%, respectively). The sensitivity of v-XM was 100%; this high value was related to the lack of false-negative DSA results. The limited specificity with both techniques (CDC-XM, 74%; FC-XM, 79%) was due to the presence of “acceptable” and/or anti-DQA/DPB DSA in some patient sera used to perform the a-XMs. During the study period, 171 (67%) of the 256 sensitized patients received a kidney transplant: 30% of these had “acceptable DSA” and/or anti-DQA/DPB DSA. No antibody-mediated rejection due to preformed HLA-DSA was observed. Conclusions Our v-XM protocol showed high sensitivity in predicting donor-recipient immunologic compatibility. The results of this study also demonstrated the importance of evaluating DSA strength for implementing v-XM results in the selection of kidney transplant recipients. Moreover, the finding of anti-DQA/DPB DSA, especially in serum samples that gave positive results with the use of both CDC and FC a-XMs, highlights the importance of defining all of the donor HLA molecules to perform an accurate v-XM.</description><subject>Antibodies - analysis</subject><subject>Donor Selection</subject><subject>Female</subject><subject>Flow Cytometry</subject><subject>Histocompatibility Testing - methods</subject><subject>HLA Antigens - immunology</subject><subject>Humans</subject><subject>Italy</subject><subject>Kidney Transplantation</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Retrospective Studies</subject><subject>Surgery</subject><issn>0041-1345</issn><issn>1873-2623</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><recordid>eNqNkU1P3EAMhkcVqCy0f6FaceJAgj0fyYYDEtrSgorUQ2nV22gy44hZsgnMJEj77zvZBQlx6smy_Nqv_ZixY4QcAYuzVT4E08XH0Fsil3NAmUOZgxIf2AwXpch4wcUemwFIzFBIdcAOY1xByrkUH9kBV1zyUlYzdvrHh2E07XwZ-hjXZrD3c9_Nf3jX0WZ-t_VpTTeYwffdJ7bfmDbS55d4xH5_u7pbXme3P7_fLC9vMyuFGjIpERZQSQPSCsdrwRtXq0oJW2PtasvLUiEhWHCqckUDjaiw5mQduFKWC3HETnZz04lPI8VBr3201KZFqB-jRlUkI6y20vOd1E77B2r0Y_BrEzYaQU-09Eq_paUnWhpKnWil5i8vPmO9TrXX1lc8SfB1J6B07bOnoKP11FlyPpAdtOv9__lcvBtjW995a9oH2lBc9WPoEk-NOnIN-tf0t-ltKAEKCX_FP3zTlmM</recordid><startdate>20140901</startdate><enddate>20140901</enddate><creator>Piazza, A</creator><creator>Ozzella, G</creator><creator>Poggi, E</creator><creator>Caputo, D</creator><creator>Manfreda, A</creator><creator>Adorno, D</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20140901</creationdate><title>Virtual Crossmatch in Kidney Transplantation</title><author>Piazza, A ; Ozzella, G ; Poggi, E ; Caputo, D ; Manfreda, A ; Adorno, D</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c435t-44108094a04c3d2b32fdb5953cb1bdbc27751e10c0d59d6f0f391b2ecd0d74783</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Antibodies - analysis</topic><topic>Donor Selection</topic><topic>Female</topic><topic>Flow Cytometry</topic><topic>Histocompatibility Testing - methods</topic><topic>HLA Antigens - immunology</topic><topic>Humans</topic><topic>Italy</topic><topic>Kidney Transplantation</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Retrospective Studies</topic><topic>Surgery</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Piazza, A</creatorcontrib><creatorcontrib>Ozzella, G</creatorcontrib><creatorcontrib>Poggi, E</creatorcontrib><creatorcontrib>Caputo, D</creatorcontrib><creatorcontrib>Manfreda, A</creatorcontrib><creatorcontrib>Adorno, D</creatorcontrib><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>Piazza, A</au><au>Ozzella, G</au><au>Poggi, E</au><au>Caputo, D</au><au>Manfreda, A</au><au>Adorno, D</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Virtual Crossmatch in Kidney Transplantation</atitle><jtitle>Transplantation proceedings</jtitle><addtitle>Transplant Proc</addtitle><date>2014-09-01</date><risdate>2014</risdate><volume>46</volume><issue>7</issue><spage>2195</spage><epage>2198</epage><pages>2195-2198</pages><issn>0041-1345</issn><eissn>1873-2623</eissn><abstract>Abstract Background The Luminex Single-Antigen Beads (LSA) assay allows an accurate detection and characterization of preexisting donor-specific antibodies (DSA) in kidney transplant candidates. But the ability of LSA to detect quite low levels of antibodies makes it hard to correctly predict crossmatch results in donor selection. In this study we retrospectively analyzed the accuracy of our virtual crossmatch (v-XM) protocol, which was used for selection of potential kidney transplant recipients, in predicting the results of actual crossmatch (a-XM) in cadaver-donor renal transplantation. We also investigated correlation between negative a-XM results and strength/specificity of preformed DSA. Methods The correlation between negative v-XMs and a-XMs performed in 2007–2012 at the Regional Transplant Center of the Lazio Region, Italy, was analyzed. In carrying out v-XM, the donor HLA molecules against which patients showed LSA-detected DSA with normalized mean fluorescence intensity (MFI) ≥5,000 were considered to be “unacceptable DSA,” and LSA-DSA showing MFI &lt;5,000 were defined as “acceptable DSA.” All cadaver donors had been typed for HLA-A, -B, -DR, and -DQB molecules by sequence-specific primer methods. On the basis of a negative v-XM, we performed 507 a-XMs between serum samples from 256 renal transplant candidates and T/B lymphocytes from 302 cadaver donors with the use of both complement-dependent cytotoxicity (CDC) and flow cytometry (FC) methods. Results The v-XM negative results showed good correlation with both CDC and FC a-XMs (97% and 90%, respectively). The sensitivity of v-XM was 100%; this high value was related to the lack of false-negative DSA results. The limited specificity with both techniques (CDC-XM, 74%; FC-XM, 79%) was due to the presence of “acceptable” and/or anti-DQA/DPB DSA in some patient sera used to perform the a-XMs. During the study period, 171 (67%) of the 256 sensitized patients received a kidney transplant: 30% of these had “acceptable DSA” and/or anti-DQA/DPB DSA. No antibody-mediated rejection due to preformed HLA-DSA was observed. Conclusions Our v-XM protocol showed high sensitivity in predicting donor-recipient immunologic compatibility. The results of this study also demonstrated the importance of evaluating DSA strength for implementing v-XM results in the selection of kidney transplant recipients. Moreover, the finding of anti-DQA/DPB DSA, especially in serum samples that gave positive results with the use of both CDC and FC a-XMs, highlights the importance of defining all of the donor HLA molecules to perform an accurate v-XM.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>25242749</pmid><doi>10.1016/j.transproceed.2014.07.053</doi><tpages>4</tpages></addata></record>
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subjects Antibodies - analysis
Donor Selection
Female
Flow Cytometry
Histocompatibility Testing - methods
HLA Antigens - immunology
Humans
Italy
Kidney Transplantation
Male
Middle Aged
Retrospective Studies
Surgery
title Virtual Crossmatch in Kidney Transplantation
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