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Erschienen in: Pediatric Nephrology 11/2011

01.11.2011 | Review

Evaluation of the highly sensitized transplant recipient

verfasst von: Peter Stastny, Ian-Michael Salvador, Bhavna Lavingia

Erschienen in: Pediatric Nephrology | Ausgabe 11/2011

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Abstract

The immune response against alloantigens involves the production of antibodies and development of T-cell immunity. Recipients sensitized to HLA antigens may have antibodies to almost all donors and may not be able to find a suitable kidney transplant donor. Strategies available to enable these patients to obtain a transplant are to give priority to highly sensitized patients, to perform therapy for antibody reduction or to transplant with existing antibodies and to intervene as needed with post-transplant treatment. While sensitization against HLA antigens is the most important cause of immunological transplant failure, other types of alloantigens, many of them expressed selectively in endothelial cells, and autoantigens may also be involved. Molecular typing and solid-phase antibody testing have markedly changed this field in the last few years. Methods for the analysis of HLA antibodies and for the study of T-cell reactivity and sensitization will also be discussed. Virtual cross-matching can now be performed for many patients, resulting in considerable savings in time and effort. Successful application of this approach requires the intervention of highly trained personnel with a good understanding of the limitations of the procedure and with intimate knowledge of the antibody profiles of the patients on the waiting list.
Literatur
1.
Zurück zum Zitat Sanfilippo F, Vaughn WK, Bollinger RR, Spees EK (1982) Comparative effects of pregnancy, transfusion, and prior graft rejection on sensitization and renal transplant results. Transplantation 34:360–366CrossRef Sanfilippo F, Vaughn WK, Bollinger RR, Spees EK (1982) Comparative effects of pregnancy, transfusion, and prior graft rejection on sensitization and renal transplant results. Transplantation 34:360–366CrossRef
2.
Zurück zum Zitat Kissmeyer-Nielsen F, Olsen S, Petersen VP, Fjeldborg O (1966) Hyperacute rejection of kidney allografts, associated with pre-existing humoral antibodies against donor cells. Lancet 2:662–665CrossRef Kissmeyer-Nielsen F, Olsen S, Petersen VP, Fjeldborg O (1966) Hyperacute rejection of kidney allografts, associated with pre-existing humoral antibodies against donor cells. Lancet 2:662–665CrossRef
3.
Zurück zum Zitat Patel R, Terasaki PI (1969) Significance of the positive crossmatch test in kidney transplantation. N Engl J Med 280:735–739CrossRef Patel R, Terasaki PI (1969) Significance of the positive crossmatch test in kidney transplantation. N Engl J Med 280:735–739CrossRef
4.
Zurück zum Zitat Moraes JR, Stastny P (1977) A new antigen system expressed in human endothelial cells. J Clin Invest 60:449–454CrossRef Moraes JR, Stastny P (1977) A new antigen system expressed in human endothelial cells. J Clin Invest 60:449–454CrossRef
5.
Zurück zum Zitat Win TS, Pettigrew GJ (2010) Humoral autoimmunity and transplant vasculopathy: when allo is not enough. Transplantation 90:113–120CrossRef Win TS, Pettigrew GJ (2010) Humoral autoimmunity and transplant vasculopathy: when allo is not enough. Transplantation 90:113–120CrossRef
6.
Zurück zum Zitat Pei R, Lee JH, Shih NJ, Chen M, Terasaki PI (2003) Single human leukocyte antigen flow cytometry beads for accurate identification of human leukocyte antigen antibody specificities. Transplantation 75:43–49CrossRef Pei R, Lee JH, Shih NJ, Chen M, Terasaki PI (2003) Single human leukocyte antigen flow cytometry beads for accurate identification of human leukocyte antigen antibody specificities. Transplantation 75:43–49CrossRef
7.
Zurück zum Zitat Waanders MM, Heidt S, Koekkoek KM, Zoet YM, Doxiadis II, Amir A, Heemskerk MH, Mulder A, Brand A, Roelen DL, Claas FH, Ward FE, MacQueen JM, Amos DB, Delmas-Marsalet Y, Johnson A (2008) Monitoring of indirect allorecognition: wishful thinking or solid data? The antiglobulin microcytotoxicity assay in HL-A genotyped families. Tissue Antigens 71:1–15CrossRef Waanders MM, Heidt S, Koekkoek KM, Zoet YM, Doxiadis II, Amir A, Heemskerk MH, Mulder A, Brand A, Roelen DL, Claas FH, Ward FE, MacQueen JM, Amos DB, Delmas-Marsalet Y, Johnson A (2008) Monitoring of indirect allorecognition: wishful thinking or solid data? The antiglobulin microcytotoxicity assay in HL-A genotyped families. Tissue Antigens 71:1–15CrossRef
8.
Zurück zum Zitat Ward FE, MacQueen JM, Amos DB, Delmas-Marsalet Y, Johnson A (1975) The antiglobulin microcytotoxicity assay in HL-A genotyped families. Transplantation 19:286–290CrossRef Ward FE, MacQueen JM, Amos DB, Delmas-Marsalet Y, Johnson A (1975) The antiglobulin microcytotoxicity assay in HL-A genotyped families. Transplantation 19:286–290CrossRef
9.
Zurück zum Zitat Karpinski M, Rush D, Jeffery J, Exner M, Regele H, Dancea S, Pochinco D, Birk P, Nickerson P (2001) Flow cytometric crossmatching in primary renal transplant recipients with a negative anti-human globulin enhanced cytotoxicity crossmatch. J Am Soc Nephrol 12:2807–2814PubMed Karpinski M, Rush D, Jeffery J, Exner M, Regele H, Dancea S, Pochinco D, Birk P, Nickerson P (2001) Flow cytometric crossmatching in primary renal transplant recipients with a negative anti-human globulin enhanced cytotoxicity crossmatch. J Am Soc Nephrol 12:2807–2814PubMed
10.
Zurück zum Zitat El-Awar N, Lee J, Terasaki PI (2005) HLA antibody identification with single antigen beads compared to conventional methods. Hum Immunol 66:989–997CrossRef El-Awar N, Lee J, Terasaki PI (2005) HLA antibody identification with single antigen beads compared to conventional methods. Hum Immunol 66:989–997CrossRef
11.
Zurück zum Zitat SEOPF (1993) Southeastern organ procurement foundation tissue typing manual. Section B-20:12-13 SEOPF (1993) Southeastern organ procurement foundation tissue typing manual. Section B-20:12-13
12.
Zurück zum Zitat Rebibou JM, Chabod J, Bittencourt MC, Thevenin C, Chalopin JM, Herve P, Tiberghien P (2000) Flow-PRA evaluation for antibody screening in patients awaiting kidney transplantation. Transplant Proc 32:2745–2746CrossRef Rebibou JM, Chabod J, Bittencourt MC, Thevenin C, Chalopin JM, Herve P, Tiberghien P (2000) Flow-PRA evaluation for antibody screening in patients awaiting kidney transplantation. Transplant Proc 32:2745–2746CrossRef
13.
Zurück zum Zitat Cecka JM (2009) Calculated PRA (CPRA): the new measure of sensitization for transplant candidates. Am J Transplant 10:26–29CrossRef Cecka JM (2009) Calculated PRA (CPRA): the new measure of sensitization for transplant candidates. Am J Transplant 10:26–29CrossRef
14.
Zurück zum Zitat Amos DB, Bach FH (1968) Phenotypic expressions of the major histocompatibility locus in man (HL-A): leukocyte antigens and mixed leukocyte culture reactivity. J Exp Med 128:623–637CrossRef Amos DB, Bach FH (1968) Phenotypic expressions of the major histocompatibility locus in man (HL-A): leukocyte antigens and mixed leukocyte culture reactivity. J Exp Med 128:623–637CrossRef
15.
Zurück zum Zitat Grunnet N, Kristensen T, Kornerup HJ, Kissmeyer-Nielsen F (1975) Direct cell mediated lympholysis. A test of allograft-rejection in human kidney recipients. Tissue Antigens 5:280–285CrossRef Grunnet N, Kristensen T, Kornerup HJ, Kissmeyer-Nielsen F (1975) Direct cell mediated lympholysis. A test of allograft-rejection in human kidney recipients. Tissue Antigens 5:280–285CrossRef
16.
Zurück zum Zitat Poggio ED, Heeger PS (2004) Use of cytokine enzyme-linked immunosorbent spot (ELISPOT) assay as an immune monitoring tool in solid organ transplantation. Transplant Rev 18:183–191CrossRef Poggio ED, Heeger PS (2004) Use of cytokine enzyme-linked immunosorbent spot (ELISPOT) assay as an immune monitoring tool in solid organ transplantation. Transplant Rev 18:183–191CrossRef
17.
Zurück zum Zitat Gupta S, Mitchell JD, Markham DW, Mammen PP, Patel PC, Kaiser PA, Stastny P, Ring WS, Dimaio JM, Drazner MH (2008) Utility of the cylex assay in cardiac transplant recipients. J Heart Lung Transplant 27:817–822CrossRef Gupta S, Mitchell JD, Markham DW, Mammen PP, Patel PC, Kaiser PA, Stastny P, Ring WS, Dimaio JM, Drazner MH (2008) Utility of the cylex assay in cardiac transplant recipients. J Heart Lung Transplant 27:817–822CrossRef
18.
Zurück zum Zitat Stastny P, Lavingia B, Fixler DE, Yancy CW, Ring WS (2007) Antibodies against donor human leukocyte antigens and the outcome of cardiac allografts in adults and children. Transplantation 84:738–745CrossRef Stastny P, Lavingia B, Fixler DE, Yancy CW, Ring WS (2007) Antibodies against donor human leukocyte antigens and the outcome of cardiac allografts in adults and children. Transplantation 84:738–745CrossRef
19.
Zurück zum Zitat Everly MJ, Rebellato LM, Ozawa M, Briley KP, Catrou PG, Haisch CE, Terasaki PI (2010) Beyond histology: lowering human leukocyte antigen antibody to improve renal allograft survival in acute rejection. Transplantation 89:962–967CrossRef Everly MJ, Rebellato LM, Ozawa M, Briley KP, Catrou PG, Haisch CE, Terasaki PI (2010) Beyond histology: lowering human leukocyte antigen antibody to improve renal allograft survival in acute rejection. Transplantation 89:962–967CrossRef
20.
Zurück zum Zitat Lobo PI, Isaacs RB, Spencer CE, Pruett TL, Sanfey HA, Sawyer RG, McCullough C (2002) Improved specificity and sensitivity when using pronase-digested lymphocytes to perform flow-cytometric crossmatch prior to renal transplantation. Transpl Int 15:563–569CrossRef Lobo PI, Isaacs RB, Spencer CE, Pruett TL, Sanfey HA, Sawyer RG, McCullough C (2002) Improved specificity and sensitivity when using pronase-digested lymphocytes to perform flow-cytometric crossmatch prior to renal transplantation. Transpl Int 15:563–569CrossRef
21.
Zurück zum Zitat Lefaucheur C, Suberbielle-Boissel C, Hill GS, Nochy D, Andrade J, Antoine C, Gautreau C, Charron D, Glotz D (2009) Clinical relevance of preformed HLA donor-specific antibodies in kidney transplantation. Contrib Nephrol 162:1–12PubMed Lefaucheur C, Suberbielle-Boissel C, Hill GS, Nochy D, Andrade J, Antoine C, Gautreau C, Charron D, Glotz D (2009) Clinical relevance of preformed HLA donor-specific antibodies in kidney transplantation. Contrib Nephrol 162:1–12PubMed
22.
Zurück zum Zitat Hidalgo LG, Campbell PM, Sis B, Einecke G, Mengel M, Chang J, Sellares J, Reeve J, Halloran PF (2009) De novo donor-specific antibody at the time of kidney transplant biopsy associates with microvascular pathology and late graft failure. Am J Transplant 9:2532–2541CrossRef Hidalgo LG, Campbell PM, Sis B, Einecke G, Mengel M, Chang J, Sellares J, Reeve J, Halloran PF (2009) De novo donor-specific antibody at the time of kidney transplant biopsy associates with microvascular pathology and late graft failure. Am J Transplant 9:2532–2541CrossRef
23.
Zurück zum Zitat Lefaucheur C, Loupy A, Hill GS, Andrade J, Nochy D, Antoine C, Gautreau C, Charron D, Glotz D, Suberbielle-Boissel C (1398) Preexisting donor-specific HLA antibodies predict outcome in kidney transplantation. J Am Soc Nephrol 21:1398–1406CrossRef Lefaucheur C, Loupy A, Hill GS, Andrade J, Nochy D, Antoine C, Gautreau C, Charron D, Glotz D, Suberbielle-Boissel C (1398) Preexisting donor-specific HLA antibodies predict outcome in kidney transplantation. J Am Soc Nephrol 21:1398–1406CrossRef
24.
Zurück zum Zitat Muczynski KA, Ekle DM, Coder DM, Anderson SK (2003) Normal human kidney HLA-DR-expressing renal microvascular endothelial cells: characterization, isolation, and regulation of MHC class II expression. J Am Soc Nephrol 14:1336–1348CrossRef Muczynski KA, Ekle DM, Coder DM, Anderson SK (2003) Normal human kidney HLA-DR-expressing renal microvascular endothelial cells: characterization, isolation, and regulation of MHC class II expression. J Am Soc Nephrol 14:1336–1348CrossRef
25.
Zurück zum Zitat Opelz G (2005) Non-HLA transplantation immunity revealed by lymphocytotoxic antibodies. Lancet 365:1570–1576CrossRef Opelz G (2005) Non-HLA transplantation immunity revealed by lymphocytotoxic antibodies. Lancet 365:1570–1576CrossRef
26.
Zurück zum Zitat Lavingia B, Qin Z, Comeaux A, Stastny P (2008) Correlation of antibodies against endothelial cell antigens with outcome of kidney regrafts. Hum Immunol 69:S108–S109CrossRef Lavingia B, Qin Z, Comeaux A, Stastny P (2008) Correlation of antibodies against endothelial cell antigens with outcome of kidney regrafts. Hum Immunol 69:S108–S109CrossRef
27.
Zurück zum Zitat Lavingia B, Comeaux A, Qin Z, Stastny P (2009) Anti-endothelial cell antibodies correlate with the development of TCAD in heart transplant recipients. Hum Immunol 70:S85CrossRef Lavingia B, Comeaux A, Qin Z, Stastny P (2009) Anti-endothelial cell antibodies correlate with the development of TCAD in heart transplant recipients. Hum Immunol 70:S85CrossRef
28.
Zurück zum Zitat Bell SA, Faust H, Mittermuller J, Kolb HJ, Meurer M (1996) Specificity of antinuclear antibodies in scleroderma-like chronic graft-versus-host disease: clinical correlation and histocompatibility locus antigen association. Br J Dermatol 134:848–854CrossRef Bell SA, Faust H, Mittermuller J, Kolb HJ, Meurer M (1996) Specificity of antinuclear antibodies in scleroderma-like chronic graft-versus-host disease: clinical correlation and histocompatibility locus antigen association. Br J Dermatol 134:848–854CrossRef
29.
Zurück zum Zitat Hirata D, Iwamoto M, Yoshio T, Okazaki H, Masuyama J, Mimori A, Minota S (2000) Nucleolin as the earliest target molecule of autoantibodies produced in MRL/lpr lupus-prone mice. Clin Immunol 97:50–58CrossRef Hirata D, Iwamoto M, Yoshio T, Okazaki H, Masuyama J, Mimori A, Minota S (2000) Nucleolin as the earliest target molecule of autoantibodies produced in MRL/lpr lupus-prone mice. Clin Immunol 97:50–58CrossRef
30.
Zurück zum Zitat Fogal V, Sugahara KN, Ruoslahti E, Christian S (2009) Cell surface nucleolin antagonist causes endothelial cell apoptosis and normalization of tumor vasculature. Angiogenesis 12:91–100CrossRef Fogal V, Sugahara KN, Ruoslahti E, Christian S (2009) Cell surface nucleolin antagonist causes endothelial cell apoptosis and normalization of tumor vasculature. Angiogenesis 12:91–100CrossRef
31.
Zurück zum Zitat Mizutani K, Terasaki P, Rosen A, Esquenazi V, Miller J, Shih RN, Pei R, Ozawa M, Lee J (2005) Serial ten-year follow-up of HLA and MICA antibody production prior to kidney graft failure. Am J Transplant 5:2265–2272CrossRef Mizutani K, Terasaki P, Rosen A, Esquenazi V, Miller J, Shih RN, Pei R, Ozawa M, Lee J (2005) Serial ten-year follow-up of HLA and MICA antibody production prior to kidney graft failure. Am J Transplant 5:2265–2272CrossRef
32.
Zurück zum Zitat Lee PC, Zhu L, Terasaki PI, Everly MJ (2009) HLA-specific antibodies developed in the first year posttransplant are predictive of chronic rejection and renal graft loss. Transplantation 88:568–574CrossRef Lee PC, Zhu L, Terasaki PI, Everly MJ (2009) HLA-specific antibodies developed in the first year posttransplant are predictive of chronic rejection and renal graft loss. Transplantation 88:568–574CrossRef
Metadaten
Titel
Evaluation of the highly sensitized transplant recipient
verfasst von
Peter Stastny
Ian-Michael Salvador
Bhavna Lavingia
Publikationsdatum
01.11.2011
Verlag
Springer Berlin Heidelberg
Erschienen in
Pediatric Nephrology / Ausgabe 11/2011
Print ISSN: 0931-041X
Elektronische ISSN: 1432-198X
DOI
https://doi.org/10.1007/s00467-010-1732-6

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