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Erschienen in: Pediatric Nephrology 6/2012

01.06.2012 | Original Article

Donor-specific HLA antibodies and graft function in children after renal transplantation

verfasst von: Jenni Miettinen, Juha Peräsaari, Jouni Lauronen, Erik Qvist, Helena Valta, Mikko Pakarinen, Jussi Merenmies, Hannu Jalanko

Erschienen in: Pediatric Nephrology | Ausgabe 6/2012

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Abstract

Background

The presence of circulating donor-specific human leukocyte antigen antibodies (HLA-DSA) has been associated with chronic antibody-mediated rejection, leading to progressive graft dysfunction and poor graft survival. The aim of this study was to investigate the incidence and significance of HLA-DSA in paediatric renal transplantation (RTx) patients.

Methods

A total of 294 post-transplant serum samples from 123 RTx patients were retrospectively analysed for HLA antibodies. Positive samples were further tested for HLA-DSA by a Luminex Single Antigen bead assay. The antibody findings were correlated to measured glomerular filtration rate (GFR) and clinical outcome.

Results

HLA antibodies were detected in half of the routine samples (140/294) taken 1 month to 10 years after RTx, and 40% (62/140) of these were HLA-DSA. Overall, one-third (42/123) of the patients had HLA-DSA, which mostly (65%) reacted against class II antigens. Detection of HLA-DSA was not associated with poor GFR at the time of sampling, and no exceptional deterioration of GFR after the HLA-DSA detection was noted in individual patients regardless of the antibody level. The presence of HLA-DSA in the first 2 years posttransplantation was not associated with poorer graft function later on.

Conclusion

Detection of HLA antibodies is common in children after RTx, and this finding, as such, does not predict any deterioration of graft function.
Literatur
1.
Zurück zum Zitat Meier-Kriesche HU, Schold JD, Kaplan B (2004) Long-term renal allograft survival: have we made significant progress or is it time to rethink our analytic and therapeutic strategies? Am J Transplant 4:1289–1295PubMedCrossRef Meier-Kriesche HU, Schold JD, Kaplan B (2004) Long-term renal allograft survival: have we made significant progress or is it time to rethink our analytic and therapeutic strategies? Am J Transplant 4:1289–1295PubMedCrossRef
2.
Zurück zum Zitat Gaston RS, Cecka JM, Kasiske BL, Fieberg AM, Leduc R, Cosio FC, Gourishankar S, Grande J, Halloran P, Hunsicker L, Mannon R, Rush D, Matas AJ (2010) Evidence for antibody-mediated injury as a major determinant of late kidney allograft failure. Transplantation 90:68–74PubMedCrossRef Gaston RS, Cecka JM, Kasiske BL, Fieberg AM, Leduc R, Cosio FC, Gourishankar S, Grande J, Halloran P, Hunsicker L, Mannon R, Rush D, Matas AJ (2010) Evidence for antibody-mediated injury as a major determinant of late kidney allograft failure. Transplantation 90:68–74PubMedCrossRef
3.
Zurück zum Zitat Nankivell BJ, Borrows RJ, Fung CL, O’Connell PJ, Allen RD, Chapman JR (2003) The natural history of chronic allograft nephropathy. N Engl J Med 349:2326–2333PubMedCrossRef Nankivell BJ, Borrows RJ, Fung CL, O’Connell PJ, Allen RD, Chapman JR (2003) The natural history of chronic allograft nephropathy. N Engl J Med 349:2326–2333PubMedCrossRef
4.
Zurück zum Zitat Akalin E, Pascual M (2006) Sensitization after kidney transplantation. Clin J Am Soc Nephrol 1:433–440PubMedCrossRef Akalin E, Pascual M (2006) Sensitization after kidney transplantation. Clin J Am Soc Nephrol 1:433–440PubMedCrossRef
5.
Zurück zum Zitat Terasaki PI, Cai J (2008) Human leukocyte antigen antibodies and chronic rejection: from association to causation. Transplantation 86:377–383PubMedCrossRef Terasaki PI, Cai J (2008) Human leukocyte antigen antibodies and chronic rejection: from association to causation. Transplantation 86:377–383PubMedCrossRef
6.
Zurück zum Zitat Böhmig GA, Bartel G, Regele H, Wahrmann M (2009) Prospects and limitations of post-transplantation alloantibody detection in renal transplantation. Hum Immunol 70:640–644PubMedCrossRef Böhmig GA, Bartel G, Regele H, Wahrmann M (2009) Prospects and limitations of post-transplantation alloantibody detection in renal transplantation. Hum Immunol 70:640–644PubMedCrossRef
7.
Zurück zum Zitat Jordan SC, Reinsmoen N, Peng A, Lai CH, Cao K, Villicana R, Toyoda M, Kahwaji J, Vo AA (2010) Advances in diagnosing and managing antibody-mediated rejection. Pediatr Nephrol 25:2035–2045PubMedCrossRef Jordan SC, Reinsmoen N, Peng A, Lai CH, Cao K, Villicana R, Toyoda M, Kahwaji J, Vo AA (2010) Advances in diagnosing and managing antibody-mediated rejection. Pediatr Nephrol 25:2035–2045PubMedCrossRef
8.
Zurück zum Zitat Riethmüller S, Ferrari-Lacraz S, Müller MK, Raptis DA, Hadaya K, Rüsi B, Laube G, Schneiter G, Fehr T, Villard J (2010) Donor-specific antibody levels and three generations of crossmatches to predict antibody-mediated rejection in kidney transplantation. Transplantation 90:160–167PubMedCrossRef Riethmüller S, Ferrari-Lacraz S, Müller MK, Raptis DA, Hadaya K, Rüsi B, Laube G, Schneiter G, Fehr T, Villard J (2010) Donor-specific antibody levels and three generations of crossmatches to predict antibody-mediated rejection in kidney transplantation. Transplantation 90:160–167PubMedCrossRef
9.
Zurück zum Zitat Cai J, Terasaki PI (2008) Post-transplantation antibody monitoring and HLA antibody epitope identification. Curr Opin Immunol 20:602–606PubMedCrossRef Cai J, Terasaki PI (2008) Post-transplantation antibody monitoring and HLA antibody epitope identification. Curr Opin Immunol 20:602–606PubMedCrossRef
10.
Zurück zum Zitat Lachmann N, Terasaki PI, Budde K, Liefeldt L, Kahl A, Reinke P, Pratschke J, Rudolph B, Schmidt D, Salama A, Schönemann C (2009) Anti-human leukocyte antigen and donor-specific antibodies detected by Luminex posttransplant serve as biomarkers for chronic rejection of renal allografts. Transplantation 87:1505–1513PubMedCrossRef Lachmann N, Terasaki PI, Budde K, Liefeldt L, Kahl A, Reinke P, Pratschke J, Rudolph B, Schmidt D, Salama A, Schönemann C (2009) Anti-human leukocyte antigen and donor-specific antibodies detected by Luminex posttransplant serve as biomarkers for chronic rejection of renal allografts. Transplantation 87:1505–1513PubMedCrossRef
11.
Zurück zum Zitat Hourmant M, Cesbron-Gautier A, Terasaki PI, Mizutani K, Moreau A, Meurette A, Dantal J, Giral M, Blancho G, Cantarovich D, Karam G, Follea G, Soulillou JP, Bignon JD (2005) Frequency and clinical implications of development of donor-specific and non-donor-specific HLA antibodies after kidney transplantation. J Am Soc Nephrol 16:2804–2812PubMedCrossRef Hourmant M, Cesbron-Gautier A, Terasaki PI, Mizutani K, Moreau A, Meurette A, Dantal J, Giral M, Blancho G, Cantarovich D, Karam G, Follea G, Soulillou JP, Bignon JD (2005) Frequency and clinical implications of development of donor-specific and non-donor-specific HLA antibodies after kidney transplantation. J Am Soc Nephrol 16:2804–2812PubMedCrossRef
12.
Zurück zum Zitat Claas FH (2010) Clinical relevance of circulating donor-specific HLA antibodies. Curr Opin Organ Transplant 15:462–466PubMedCrossRef Claas FH (2010) Clinical relevance of circulating donor-specific HLA antibodies. Curr Opin Organ Transplant 15:462–466PubMedCrossRef
13.
Zurück zum Zitat Lee PC, Terasaki PI, Takemoto SK, Lee PH, Hung CJ, Chen YL, Tsai A, Lei HY (2002) All chronic rejection failures of kidney transplants were preceded by the development of HLA antibodies. Transplantation 74:1192–1194PubMedCrossRef Lee PC, Terasaki PI, Takemoto SK, Lee PH, Hung CJ, Chen YL, Tsai A, Lei HY (2002) All chronic rejection failures of kidney transplants were preceded by the development of HLA antibodies. Transplantation 74:1192–1194PubMedCrossRef
14.
Zurück zum Zitat Terasaki PI, Ozawa M, Castro R (2007) Four-year follow-up of a prospective trial of HLA and MICA antibodies on kidney graft survival. Am J Transplant 7:408–415PubMedCrossRef Terasaki PI, Ozawa M, Castro R (2007) Four-year follow-up of a prospective trial of HLA and MICA antibodies on kidney graft survival. Am J Transplant 7:408–415PubMedCrossRef
15.
Zurück zum Zitat Phelan D, Mohanakumar T, Ramachandran S, Jendrisak MD (2009) Living donor renal transplantation in the presence of donor-specific human leukocyte antigen antibody detected by solid-phase assay. Hum Immunol 70:584–588PubMedCrossRef Phelan D, Mohanakumar T, Ramachandran S, Jendrisak MD (2009) Living donor renal transplantation in the presence of donor-specific human leukocyte antigen antibody detected by solid-phase assay. Hum Immunol 70:584–588PubMedCrossRef
16.
Zurück zum Zitat Aubert V, Venetz JP, Pantaleo G, Pascual M (2009) Are all donor-specific antibodies detected by solid-phase assay before transplantation clinically relevant? Transplantation 87:1897–1898PubMedCrossRef Aubert V, Venetz JP, Pantaleo G, Pascual M (2009) Are all donor-specific antibodies detected by solid-phase assay before transplantation clinically relevant? Transplantation 87:1897–1898PubMedCrossRef
17.
Zurück zum Zitat Bartel G, Regele H, Wahrmann M, Huttary N, Exner M, Hörl WH, Böhmig GA (2008) Posttransplant HLA alloreactivity in stable kidney transplant recipients-incidences and impact on long-term allograft outcomes. Am J Transplant 8:2652–2660PubMedCrossRef Bartel G, Regele H, Wahrmann M, Huttary N, Exner M, Hörl WH, Böhmig GA (2008) Posttransplant HLA alloreactivity in stable kidney transplant recipients-incidences and impact on long-term allograft outcomes. Am J Transplant 8:2652–2660PubMedCrossRef
18.
Zurück zum Zitat Süsal C, Ovens J, Mahmoud K, Döhler B, Scherer S, Ruhenstroth A, Tran TH, Heinoid A, Opelz G (2011) No association of kidney graft loss with human leukocyte antigen antibodies detected exclusively by sensitive Luminex single-antigen testing: a Collaborative Transplant Study report. Transplantation 91:883–887PubMedCrossRef Süsal C, Ovens J, Mahmoud K, Döhler B, Scherer S, Ruhenstroth A, Tran TH, Heinoid A, Opelz G (2011) No association of kidney graft loss with human leukocyte antigen antibodies detected exclusively by sensitive Luminex single-antigen testing: a Collaborative Transplant Study report. Transplantation 91:883–887PubMedCrossRef
19.
Zurück zum Zitat Girnita AL, Webber SA, Zeevi A (2006) Anti-HLA alloantibodies in pediatric solid organ transplantation. Pediatr Transplant 10:146–153PubMedCrossRef Girnita AL, Webber SA, Zeevi A (2006) Anti-HLA alloantibodies in pediatric solid organ transplantation. Pediatr Transplant 10:146–153PubMedCrossRef
20.
Zurück zum Zitat Roberti I, Vyas S, Pancoska C (2007) Donor-specific antibodies by flow single antigen beads in pediatric living donor kidney transplants: single center experience. Pediatr Transplant 11:901–905PubMedCrossRef Roberti I, Vyas S, Pancoska C (2007) Donor-specific antibodies by flow single antigen beads in pediatric living donor kidney transplants: single center experience. Pediatr Transplant 11:901–905PubMedCrossRef
21.
Zurück zum Zitat Verghese PS, Smith JM, McDonald RA, Schwartz SM, Nelson KA, Warner PR (2010) Impaired graft survival in pediatric renal transplant recipients with donor-specific antibodies detected by solid-phase assays. Pediatr Transplant 14:730–734PubMedCrossRef Verghese PS, Smith JM, McDonald RA, Schwartz SM, Nelson KA, Warner PR (2010) Impaired graft survival in pediatric renal transplant recipients with donor-specific antibodies detected by solid-phase assays. Pediatr Transplant 14:730–734PubMedCrossRef
22.
Zurück zum Zitat Emonds MP, Herman J, Dendievel J, Waer M, Van Damme-Lombaerts R (2000) Evaluation of anti-human leukocyte antigen allo-immunization in pediatric cadaveric kidney transplantation. Pediatr Transplant 4:6–11PubMedCrossRef Emonds MP, Herman J, Dendievel J, Waer M, Van Damme-Lombaerts R (2000) Evaluation of anti-human leukocyte antigen allo-immunization in pediatric cadaveric kidney transplantation. Pediatr Transplant 4:6–11PubMedCrossRef
23.
Zurück zum Zitat Valta H, Jalanko H, Holmberg C, Helenius I, Mäkitie O (2008) Impaired bone health in adolescents after liver transplantation. Am J Transplant 8:150–157PubMed Valta H, Jalanko H, Holmberg C, Helenius I, Mäkitie O (2008) Impaired bone health in adolescents after liver transplantation. Am J Transplant 8:150–157PubMed
24.
Zurück zum Zitat Jodal L, Brochner-Mortensen J (2009) Reassessment of a classical single injection 51Cr-EDTA clearance method for determination of renal function in children and adults. Part I: Analytically correct relationship between total and one-pool clearance. Scand J Clin Lab Invest 69:305–313PubMedCrossRef Jodal L, Brochner-Mortensen J (2009) Reassessment of a classical single injection 51Cr-EDTA clearance method for determination of renal function in children and adults. Part I: Analytically correct relationship between total and one-pool clearance. Scand J Clin Lab Invest 69:305–313PubMedCrossRef
25.
Zurück zum Zitat Eng HS, Bennett G, Bardy P, Coghlan P, Russ GR, Coates PT (2009) Clinical significance of anti-HLA antibodies detected by Luminex: enhancing the interpretation of CDC-BXM and important post-transplantation monitoring tools. Hum Immunol 70:595–599PubMedCrossRef Eng HS, Bennett G, Bardy P, Coghlan P, Russ GR, Coates PT (2009) Clinical significance of anti-HLA antibodies detected by Luminex: enhancing the interpretation of CDC-BXM and important post-transplantation monitoring tools. Hum Immunol 70:595–599PubMedCrossRef
26.
Zurück zum Zitat Terasaki P, Lachmann N, Cai J (2006) Summary of the effect of de novo HLA antibodies on chronic kidney graft failure. Clin Transpl 455–462 Terasaki P, Lachmann N, Cai J (2006) Summary of the effect of de novo HLA antibodies on chronic kidney graft failure. Clin Transpl 455–462
27.
Zurück zum Zitat Amico P, Hönger G, Mayr M, Steiger J, Hopfer H, Schaub S (2009) Clinical relevance of pretransplant donor-specific HLA antibodies detected by single-antigen flow-beads. Transplantation 87:1681–1688PubMedCrossRef Amico P, Hönger G, Mayr M, Steiger J, Hopfer H, Schaub S (2009) Clinical relevance of pretransplant donor-specific HLA antibodies detected by single-antigen flow-beads. Transplantation 87:1681–1688PubMedCrossRef
28.
Zurück zum Zitat Gupta A, Sinnott P (2009) Clinical relevance of pretransplant human leukocyte antigen donor-specific antibodies in renal patients waiting for a transplant: a risk factor. Hum Immunol 70:618–622PubMedCrossRef Gupta A, Sinnott P (2009) Clinical relevance of pretransplant human leukocyte antigen donor-specific antibodies in renal patients waiting for a transplant: a risk factor. Hum Immunol 70:618–622PubMedCrossRef
29.
Zurück zum Zitat Fine RN, Malekzadeh MH, Pennisi AJ, Ettenger RB, Uittenbogaart CH, Korsch BM (1979) Renal transplantation in children. J Pediatr 95:244–248PubMedCrossRef Fine RN, Malekzadeh MH, Pennisi AJ, Ettenger RB, Uittenbogaart CH, Korsch BM (1979) Renal transplantation in children. J Pediatr 95:244–248PubMedCrossRef
30.
Zurück zum Zitat Davenport A, Younie ME, Parsons JE, Klouda PT (1994) Development of cytotoxic antibodies following renal allograft transplantation is associated with reduced graft survival due to chronic vascular rejection. Nephrol Dial Transplant 9:1315–1319PubMed Davenport A, Younie ME, Parsons JE, Klouda PT (1994) Development of cytotoxic antibodies following renal allograft transplantation is associated with reduced graft survival due to chronic vascular rejection. Nephrol Dial Transplant 9:1315–1319PubMed
31.
Zurück zum Zitat Yabu JM, Higgins JP, Chen G, Sequeira F, Busque S, Tyran DB (2011) C1q-fixing human leukocyte antigen antibodies are specific for predicting transplant glomerulopathy and late graft failure after kidney transplantation. Transplantation 91:342–347PubMedCrossRef Yabu JM, Higgins JP, Chen G, Sequeira F, Busque S, Tyran DB (2011) C1q-fixing human leukocyte antigen antibodies are specific for predicting transplant glomerulopathy and late graft failure after kidney transplantation. Transplantation 91:342–347PubMedCrossRef
32.
Zurück zum Zitat Chin C, Chen G, Sequeria F, Berry G, Siehr S, Bernstein D, Rosenthal D, Reinhartz O, Tyan D (2011) Clinical usefulness of a novel C1q assay to detect immunoglobulin G antibodies capable of fixing complement in sensitized pediatric heart transplant patients. J Heart Lung Transplant 30:158–163PubMedCrossRef Chin C, Chen G, Sequeria F, Berry G, Siehr S, Bernstein D, Rosenthal D, Reinhartz O, Tyan D (2011) Clinical usefulness of a novel C1q assay to detect immunoglobulin G antibodies capable of fixing complement in sensitized pediatric heart transplant patients. J Heart Lung Transplant 30:158–163PubMedCrossRef
Metadaten
Titel
Donor-specific HLA antibodies and graft function in children after renal transplantation
verfasst von
Jenni Miettinen
Juha Peräsaari
Jouni Lauronen
Erik Qvist
Helena Valta
Mikko Pakarinen
Jussi Merenmies
Hannu Jalanko
Publikationsdatum
01.06.2012
Verlag
Springer-Verlag
Erschienen in
Pediatric Nephrology / Ausgabe 6/2012
Print ISSN: 0931-041X
Elektronische ISSN: 1432-198X
DOI
https://doi.org/10.1007/s00467-012-2101-4

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