Consensus guidelines on the testing and clinical management issues associated with HLA and Non-HLA antibodies in transplantation

Brian D. Tait, Caner Süsal, Howard M. Gebel, Peter W. Nickerson, Andrea A. Zachary, Frans H J Claas, Elaine F. Reed, Robert A. Bray, Patricia Campbell, Jeremy R. Chapman, P. Toby Coates, Robert B. Colvin, Emanuele Cozzi, Ilias I N Doxiadis, Susan V. Fuggle, John Gill, Denis Glotz, Nils Lachmann, Thalachallour Mohanakumar, Nicole Suciu-FocaSuchitra Sumitran-Holgersson, Kazunari Tanabe, Craig J. Taylor, Dolly B. Tyan, Angela Webster, Adriana Zeevi, Gerhard Opelz

Research output: Contribution to journalArticle

Abstract

BACKGROUND: The introduction of solid-phase immunoassay (SPI) technology for the detection and characterization of human leukocyte antigen (HLA) antibodies in transplantation while providing greater sensitivity than was obtainable by complement-dependent lymphocytotoxicity (CDC) assays has resulted in a new paradigm with respect to the interpretation of donor-specific antibodies (DSA). Although the SPI assay performed on the Luminex instrument (hereafter referred to as the Luminex assay), in particular, has permitted the detection of antibodies not detectable by CDC, the clinical significance of these antibodies is incompletely understood. Nevertheless, the detection of these antibodies has led to changes in the clinical management of sensitized patients. In addition, SPI testing raises technical issues that require resolution and careful consideration when interpreting antibody results. METHODS: With this background, The Transplantation Society convened a group of laboratory and clinical experts in the field of transplantation to prepare a consensus report and make recommendations on the use of this new technology based on both published evidence and expert opinion. Three working groups were formed to address (a) the technical issues with respect to the use of this technology, (b) the interpretation of pretransplantation antibody testing in the context of various clinical settings and organ transplant types (kidney, heart, lung, liver, pancreas, intestinal, and islet cells), and (c) the application of antibody testing in the posttransplantation setting. The three groups were established in November 2011 and convened for a "Consensus Conference on Antibodies in Transplantation" in Rome, Italy, in May 2012. The deliberations of the three groups meeting independently and then together are the bases for this report. RESULTS: A comprehensive list of recommendations was prepared by each group. A summary of the key recommendations follows. Technical Group: (a) SPI must be used for the detection of pretransplantation HLA antibodies in solid organ transplant recipients and, in particular, the use of the single-antigen bead assay to detect antibodies to HLA loci, such as Cw, DQA, DPA, and DPB, which are not readily detected by other methods. (b) The use of SPI for antibody detection should be supplemented with cell-based assays to examine the correlations between the two types of assays and to establish the likelihood of a positive crossmatch (XM). (c) There must be an awareness of the technical factors that can influence the results and their clinical interpretation when using the Luminex bead technology, such as variation in antigen density and the presence of denatured antigen on the beads. Pretransplantation Group: (a) Risk categories should be established based on the antibody and the XM results obtained. (b) DSA detected by CDC and a positive XM should be avoided due to their strong association with antibody-mediated rejection and graft loss. (c) A renal transplantation can be performed in the absence of a prospective XM if single-antigen bead screening for antibodies to all class I and II HLA loci is negative. This decision, however, needs to be taken in agreement with local clinical programs and the relevant regulatory bodies. (d) The presence of DSA HLA antibodies should be avoided in heart and lung transplantation and considered a risk factor for liver, intestinal, and islet cell transplantation. Posttransplantation Group: (a) High-risk patients (i.e., desensitized or DSA positive/XM negative) should be monitored by measurement of DSA and protocol biopsies in the first 3 months after transplantation. (b) Intermediate-risk patients (history of DSA but currently negative) should be monitored for DSA within the first month. If DSA is present, a biopsy should be performed. (c) Low-risk patients (nonsensitized first transplantation) should be screened for DSA at least once 3 to 12 months after transplantation. If DSA is detected, a biopsy should be performed. In all three categories, the recommendations for subsequent treatment are based on the biopsy results. CONCLUSIONS: A comprehensive list of recommendations is provided covering the technical and pretransplantation and posttransplantation monitoring of HLA antibodies in solid organ transplantation. The recommendations are intended to provide state-of-the-art guidance in the use and clinical application of recently developed methods for HLA antibody detection when used in conjunction with traditional methods.

Original languageEnglish (US)
Pages (from-to)19-47
Number of pages29
JournalTransplantation
Volume95
Issue number1
DOIs
StatePublished - Jan 15 2013

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HLA Antigens
Transplantation
Guidelines
Antibodies
Tissue Donors
Immunoassay
Technology
Biopsy
Islets of Langerhans
Antigens
Consensus

ASJC Scopus subject areas

  • Transplantation

Cite this

Tait, B. D., Süsal, C., Gebel, H. M., Nickerson, P. W., Zachary, A. A., Claas, F. H. J., ... Opelz, G. (2013). Consensus guidelines on the testing and clinical management issues associated with HLA and Non-HLA antibodies in transplantation. Transplantation, 95(1), 19-47. https://doi.org/10.1097/TP.0b013e31827a19cc

Consensus guidelines on the testing and clinical management issues associated with HLA and Non-HLA antibodies in transplantation. / Tait, Brian D.; Süsal, Caner; Gebel, Howard M.; Nickerson, Peter W.; Zachary, Andrea A.; Claas, Frans H J; Reed, Elaine F.; Bray, Robert A.; Campbell, Patricia; Chapman, Jeremy R.; Coates, P. Toby; Colvin, Robert B.; Cozzi, Emanuele; Doxiadis, Ilias I N; Fuggle, Susan V.; Gill, John; Glotz, Denis; Lachmann, Nils; Mohanakumar, Thalachallour; Suciu-Foca, Nicole; Sumitran-Holgersson, Suchitra; Tanabe, Kazunari; Taylor, Craig J.; Tyan, Dolly B.; Webster, Angela; Zeevi, Adriana; Opelz, Gerhard.

In: Transplantation, Vol. 95, No. 1, 15.01.2013, p. 19-47.

Research output: Contribution to journalArticle

Tait, BD, Süsal, C, Gebel, HM, Nickerson, PW, Zachary, AA, Claas, FHJ, Reed, EF, Bray, RA, Campbell, P, Chapman, JR, Coates, PT, Colvin, RB, Cozzi, E, Doxiadis, IIN, Fuggle, SV, Gill, J, Glotz, D, Lachmann, N, Mohanakumar, T, Suciu-Foca, N, Sumitran-Holgersson, S, Tanabe, K, Taylor, CJ, Tyan, DB, Webster, A, Zeevi, A & Opelz, G 2013, 'Consensus guidelines on the testing and clinical management issues associated with HLA and Non-HLA antibodies in transplantation', Transplantation, vol. 95, no. 1, pp. 19-47. https://doi.org/10.1097/TP.0b013e31827a19cc
Tait, Brian D. ; Süsal, Caner ; Gebel, Howard M. ; Nickerson, Peter W. ; Zachary, Andrea A. ; Claas, Frans H J ; Reed, Elaine F. ; Bray, Robert A. ; Campbell, Patricia ; Chapman, Jeremy R. ; Coates, P. Toby ; Colvin, Robert B. ; Cozzi, Emanuele ; Doxiadis, Ilias I N ; Fuggle, Susan V. ; Gill, John ; Glotz, Denis ; Lachmann, Nils ; Mohanakumar, Thalachallour ; Suciu-Foca, Nicole ; Sumitran-Holgersson, Suchitra ; Tanabe, Kazunari ; Taylor, Craig J. ; Tyan, Dolly B. ; Webster, Angela ; Zeevi, Adriana ; Opelz, Gerhard. / Consensus guidelines on the testing and clinical management issues associated with HLA and Non-HLA antibodies in transplantation. In: Transplantation. 2013 ; Vol. 95, No. 1. pp. 19-47.
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abstract = "BACKGROUND: The introduction of solid-phase immunoassay (SPI) technology for the detection and characterization of human leukocyte antigen (HLA) antibodies in transplantation while providing greater sensitivity than was obtainable by complement-dependent lymphocytotoxicity (CDC) assays has resulted in a new paradigm with respect to the interpretation of donor-specific antibodies (DSA). Although the SPI assay performed on the Luminex instrument (hereafter referred to as the Luminex assay), in particular, has permitted the detection of antibodies not detectable by CDC, the clinical significance of these antibodies is incompletely understood. Nevertheless, the detection of these antibodies has led to changes in the clinical management of sensitized patients. In addition, SPI testing raises technical issues that require resolution and careful consideration when interpreting antibody results. METHODS: With this background, The Transplantation Society convened a group of laboratory and clinical experts in the field of transplantation to prepare a consensus report and make recommendations on the use of this new technology based on both published evidence and expert opinion. Three working groups were formed to address (a) the technical issues with respect to the use of this technology, (b) the interpretation of pretransplantation antibody testing in the context of various clinical settings and organ transplant types (kidney, heart, lung, liver, pancreas, intestinal, and islet cells), and (c) the application of antibody testing in the posttransplantation setting. The three groups were established in November 2011 and convened for a {"}Consensus Conference on Antibodies in Transplantation{"} in Rome, Italy, in May 2012. The deliberations of the three groups meeting independently and then together are the bases for this report. RESULTS: A comprehensive list of recommendations was prepared by each group. A summary of the key recommendations follows. Technical Group: (a) SPI must be used for the detection of pretransplantation HLA antibodies in solid organ transplant recipients and, in particular, the use of the single-antigen bead assay to detect antibodies to HLA loci, such as Cw, DQA, DPA, and DPB, which are not readily detected by other methods. (b) The use of SPI for antibody detection should be supplemented with cell-based assays to examine the correlations between the two types of assays and to establish the likelihood of a positive crossmatch (XM). (c) There must be an awareness of the technical factors that can influence the results and their clinical interpretation when using the Luminex bead technology, such as variation in antigen density and the presence of denatured antigen on the beads. Pretransplantation Group: (a) Risk categories should be established based on the antibody and the XM results obtained. (b) DSA detected by CDC and a positive XM should be avoided due to their strong association with antibody-mediated rejection and graft loss. (c) A renal transplantation can be performed in the absence of a prospective XM if single-antigen bead screening for antibodies to all class I and II HLA loci is negative. This decision, however, needs to be taken in agreement with local clinical programs and the relevant regulatory bodies. (d) The presence of DSA HLA antibodies should be avoided in heart and lung transplantation and considered a risk factor for liver, intestinal, and islet cell transplantation. Posttransplantation Group: (a) High-risk patients (i.e., desensitized or DSA positive/XM negative) should be monitored by measurement of DSA and protocol biopsies in the first 3 months after transplantation. (b) Intermediate-risk patients (history of DSA but currently negative) should be monitored for DSA within the first month. If DSA is present, a biopsy should be performed. (c) Low-risk patients (nonsensitized first transplantation) should be screened for DSA at least once 3 to 12 months after transplantation. If DSA is detected, a biopsy should be performed. In all three categories, the recommendations for subsequent treatment are based on the biopsy results. CONCLUSIONS: A comprehensive list of recommendations is provided covering the technical and pretransplantation and posttransplantation monitoring of HLA antibodies in solid organ transplantation. The recommendations are intended to provide state-of-the-art guidance in the use and clinical application of recently developed methods for HLA antibody detection when used in conjunction with traditional methods.",
author = "Tait, {Brian D.} and Caner S{\"u}sal and Gebel, {Howard M.} and Nickerson, {Peter W.} and Zachary, {Andrea A.} and Claas, {Frans H J} and Reed, {Elaine F.} and Bray, {Robert A.} and Patricia Campbell and Chapman, {Jeremy R.} and Coates, {P. Toby} and Colvin, {Robert B.} and Emanuele Cozzi and Doxiadis, {Ilias I N} and Fuggle, {Susan V.} and John Gill and Denis Glotz and Nils Lachmann and Thalachallour Mohanakumar and Nicole Suciu-Foca and Suchitra Sumitran-Holgersson and Kazunari Tanabe and Taylor, {Craig J.} and Tyan, {Dolly B.} and Angela Webster and Adriana Zeevi and Gerhard Opelz",
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TY - JOUR

T1 - Consensus guidelines on the testing and clinical management issues associated with HLA and Non-HLA antibodies in transplantation

AU - Tait, Brian D.

AU - Süsal, Caner

AU - Gebel, Howard M.

AU - Nickerson, Peter W.

AU - Zachary, Andrea A.

AU - Claas, Frans H J

AU - Reed, Elaine F.

AU - Bray, Robert A.

AU - Campbell, Patricia

AU - Chapman, Jeremy R.

AU - Coates, P. Toby

AU - Colvin, Robert B.

AU - Cozzi, Emanuele

AU - Doxiadis, Ilias I N

AU - Fuggle, Susan V.

AU - Gill, John

AU - Glotz, Denis

AU - Lachmann, Nils

AU - Mohanakumar, Thalachallour

AU - Suciu-Foca, Nicole

AU - Sumitran-Holgersson, Suchitra

AU - Tanabe, Kazunari

AU - Taylor, Craig J.

AU - Tyan, Dolly B.

AU - Webster, Angela

AU - Zeevi, Adriana

AU - Opelz, Gerhard

PY - 2013/1/15

Y1 - 2013/1/15

N2 - BACKGROUND: The introduction of solid-phase immunoassay (SPI) technology for the detection and characterization of human leukocyte antigen (HLA) antibodies in transplantation while providing greater sensitivity than was obtainable by complement-dependent lymphocytotoxicity (CDC) assays has resulted in a new paradigm with respect to the interpretation of donor-specific antibodies (DSA). Although the SPI assay performed on the Luminex instrument (hereafter referred to as the Luminex assay), in particular, has permitted the detection of antibodies not detectable by CDC, the clinical significance of these antibodies is incompletely understood. Nevertheless, the detection of these antibodies has led to changes in the clinical management of sensitized patients. In addition, SPI testing raises technical issues that require resolution and careful consideration when interpreting antibody results. METHODS: With this background, The Transplantation Society convened a group of laboratory and clinical experts in the field of transplantation to prepare a consensus report and make recommendations on the use of this new technology based on both published evidence and expert opinion. Three working groups were formed to address (a) the technical issues with respect to the use of this technology, (b) the interpretation of pretransplantation antibody testing in the context of various clinical settings and organ transplant types (kidney, heart, lung, liver, pancreas, intestinal, and islet cells), and (c) the application of antibody testing in the posttransplantation setting. The three groups were established in November 2011 and convened for a "Consensus Conference on Antibodies in Transplantation" in Rome, Italy, in May 2012. The deliberations of the three groups meeting independently and then together are the bases for this report. RESULTS: A comprehensive list of recommendations was prepared by each group. A summary of the key recommendations follows. Technical Group: (a) SPI must be used for the detection of pretransplantation HLA antibodies in solid organ transplant recipients and, in particular, the use of the single-antigen bead assay to detect antibodies to HLA loci, such as Cw, DQA, DPA, and DPB, which are not readily detected by other methods. (b) The use of SPI for antibody detection should be supplemented with cell-based assays to examine the correlations between the two types of assays and to establish the likelihood of a positive crossmatch (XM). (c) There must be an awareness of the technical factors that can influence the results and their clinical interpretation when using the Luminex bead technology, such as variation in antigen density and the presence of denatured antigen on the beads. Pretransplantation Group: (a) Risk categories should be established based on the antibody and the XM results obtained. (b) DSA detected by CDC and a positive XM should be avoided due to their strong association with antibody-mediated rejection and graft loss. (c) A renal transplantation can be performed in the absence of a prospective XM if single-antigen bead screening for antibodies to all class I and II HLA loci is negative. This decision, however, needs to be taken in agreement with local clinical programs and the relevant regulatory bodies. (d) The presence of DSA HLA antibodies should be avoided in heart and lung transplantation and considered a risk factor for liver, intestinal, and islet cell transplantation. Posttransplantation Group: (a) High-risk patients (i.e., desensitized or DSA positive/XM negative) should be monitored by measurement of DSA and protocol biopsies in the first 3 months after transplantation. (b) Intermediate-risk patients (history of DSA but currently negative) should be monitored for DSA within the first month. If DSA is present, a biopsy should be performed. (c) Low-risk patients (nonsensitized first transplantation) should be screened for DSA at least once 3 to 12 months after transplantation. If DSA is detected, a biopsy should be performed. In all three categories, the recommendations for subsequent treatment are based on the biopsy results. CONCLUSIONS: A comprehensive list of recommendations is provided covering the technical and pretransplantation and posttransplantation monitoring of HLA antibodies in solid organ transplantation. The recommendations are intended to provide state-of-the-art guidance in the use and clinical application of recently developed methods for HLA antibody detection when used in conjunction with traditional methods.

AB - BACKGROUND: The introduction of solid-phase immunoassay (SPI) technology for the detection and characterization of human leukocyte antigen (HLA) antibodies in transplantation while providing greater sensitivity than was obtainable by complement-dependent lymphocytotoxicity (CDC) assays has resulted in a new paradigm with respect to the interpretation of donor-specific antibodies (DSA). Although the SPI assay performed on the Luminex instrument (hereafter referred to as the Luminex assay), in particular, has permitted the detection of antibodies not detectable by CDC, the clinical significance of these antibodies is incompletely understood. Nevertheless, the detection of these antibodies has led to changes in the clinical management of sensitized patients. In addition, SPI testing raises technical issues that require resolution and careful consideration when interpreting antibody results. METHODS: With this background, The Transplantation Society convened a group of laboratory and clinical experts in the field of transplantation to prepare a consensus report and make recommendations on the use of this new technology based on both published evidence and expert opinion. Three working groups were formed to address (a) the technical issues with respect to the use of this technology, (b) the interpretation of pretransplantation antibody testing in the context of various clinical settings and organ transplant types (kidney, heart, lung, liver, pancreas, intestinal, and islet cells), and (c) the application of antibody testing in the posttransplantation setting. The three groups were established in November 2011 and convened for a "Consensus Conference on Antibodies in Transplantation" in Rome, Italy, in May 2012. The deliberations of the three groups meeting independently and then together are the bases for this report. RESULTS: A comprehensive list of recommendations was prepared by each group. A summary of the key recommendations follows. Technical Group: (a) SPI must be used for the detection of pretransplantation HLA antibodies in solid organ transplant recipients and, in particular, the use of the single-antigen bead assay to detect antibodies to HLA loci, such as Cw, DQA, DPA, and DPB, which are not readily detected by other methods. (b) The use of SPI for antibody detection should be supplemented with cell-based assays to examine the correlations between the two types of assays and to establish the likelihood of a positive crossmatch (XM). (c) There must be an awareness of the technical factors that can influence the results and their clinical interpretation when using the Luminex bead technology, such as variation in antigen density and the presence of denatured antigen on the beads. Pretransplantation Group: (a) Risk categories should be established based on the antibody and the XM results obtained. (b) DSA detected by CDC and a positive XM should be avoided due to their strong association with antibody-mediated rejection and graft loss. (c) A renal transplantation can be performed in the absence of a prospective XM if single-antigen bead screening for antibodies to all class I and II HLA loci is negative. This decision, however, needs to be taken in agreement with local clinical programs and the relevant regulatory bodies. (d) The presence of DSA HLA antibodies should be avoided in heart and lung transplantation and considered a risk factor for liver, intestinal, and islet cell transplantation. Posttransplantation Group: (a) High-risk patients (i.e., desensitized or DSA positive/XM negative) should be monitored by measurement of DSA and protocol biopsies in the first 3 months after transplantation. (b) Intermediate-risk patients (history of DSA but currently negative) should be monitored for DSA within the first month. If DSA is present, a biopsy should be performed. (c) Low-risk patients (nonsensitized first transplantation) should be screened for DSA at least once 3 to 12 months after transplantation. If DSA is detected, a biopsy should be performed. In all three categories, the recommendations for subsequent treatment are based on the biopsy results. CONCLUSIONS: A comprehensive list of recommendations is provided covering the technical and pretransplantation and posttransplantation monitoring of HLA antibodies in solid organ transplantation. The recommendations are intended to provide state-of-the-art guidance in the use and clinical application of recently developed methods for HLA antibody detection when used in conjunction with traditional methods.

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