Annals of Laboratory Medicine

Korean Society for Laboratory Medicine (대한진단검사의학회)
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Application of Calculated Panel Reactive Antibody Using HLA Frequencies in Koreans

  • Jang, Ji-Young (Department of Laboratory Medicine, School of Medicine, The Catholic University of Korea) ;
  • Kim, Yoon-Joo (Department of Laboratory Medicine, School of Medicine, The Catholic University of Korea) ;
  • Kim, Yong-Goo (Department of Laboratory Medicine, School of Medicine, The Catholic University of Korea) ;
  • Park, Yeon-Joon (Department of Laboratory Medicine, School of Medicine, The Catholic University of Korea) ;
  • Han, Kyung-Ja (Department of Laboratory Medicine, School of Medicine, The Catholic University of Korea) ;
  • Oh, Eun-Jee (Department of Laboratory Medicine, School of Medicine, The Catholic University of Korea)
  • Published : 2012.01.01
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Abstract

Background: Introduction of the Luminex panel reactive antibody (PRA)-single antigen (SA) assay has increased the detection rates of unacceptable antigens in sensitized patients; the calculated PRA (CPRA) level represents the percentage of actual organ donors that express 1 or more of these unacceptable antigens. We developed a CPRA calculator based on the HLA frequencies in Koreans to measure sensitization levels in Korean patients. Methods: To develop the calculator, we obtained the HLA-A, HLA-B, and HLA-DR phenotypes of 1,622 Koreans, and compared these with previously reported frequencies in Koreans. Sera from patients awaiting kidney transplantation were tested for HLA antibodies by Luminex PRA-screen, PRA-identification (ID), and PRA-SA assays. The measured %PRA from the PRA-screen (N=55) and PRA-ID (N=71) were compared to the %CPRA for the unacceptable antigens obtained from PRA-SA. Results: Phenotype frequencies used for the CPRA calculator agreed with previously reported data. The concordance rates among the 3 PRA methods for the detection of class I and class II antibodies were 76.1-81.8% (kappa, 0.519-0.636) and 72.7-83.6% (0.463-0.650), respectively. For the detection of broadly sensitized sera (>50% or >80%), the concordance rates were over 80%. In sera with 80-100% CPRA, 91.7% and 94.4% of the samples had concordant results (80-100% PRA) in the PRA-screen and PRA-ID assay, respectively. Conclusions: Although further clinical studies are required to confirm the benefits of CPRA values, adoption of CPRA analysis based on HLA frequencies in Koreans may be useful for sensitization measurements and organ-allocation algorithms.

Keywords

References

  1. Cecka JM, Kucheryavaya AY, Reinsmoen NL, Leffell MS. Calculated PRA: initial results show benefits for sensitized patients and a reduction in positive crossmatches. Am J Transplant 2011;11:719-724. https://doi.org/10.1111/j.1600-6143.2010.03340.x
  2. Cecka JM. Calculated PRA (CPRA): the new measure of sensitization for transplant candidates. Am J Transplant 2010;10:26-29. https://doi.org/10.1111/j.1600-6143.2009.02927.x
  3. Jung S, Oh EJ, Yang CW, Ahn WS, Kim Y, Park YJ, et al. Comparative evaluation of ELISA and Luminex panel reactive antibody assays for HLA alloantibody screening. Korean J Lab Med 2009;29:473-480. https://doi.org/10.3343/kjlm.2009.29.5.473
  4. Bray RA and Gebel HM. Strategies for human leukocyte antigen antibody detection. Curr Opin Organ Transplant 2009;14:392-397. https://doi.org/10.1097/MOT.0b013e32832d31c7
  5. Howell WM, Carter V, Clark B. The HLA system: immunobiology, HLA typing, antibody screening and crossmatching techniques. J Clin Pathol 2010;63:387-390. https://doi.org/10.1136/jcp.2009.072371
  6. Roh EY, Kim HS, Kim SM, Lim YM, Han BY, Park MH. HLA-A, -B, -DR allele frequencies and haplotypic associations in Koreans defined by generic-level DNA typing. Korean J Lab Med 2003;23:420-430.
  7. Whang DH, Yang YS, Hong HK. Allele and haplotype frequencies of human leukocyte antigen-A, -B, and -DR loci in Koreans: DNA typing of 1,500 cord blood units. Korean J Lab Med 2008;28:465-474. https://doi.org/10.3343/kjlm.2008.28.6.465
  8. Raymond M and Rousset F. GENEPOP (version 1.2): population genetics software for exact tests and ecumenicism. J Hered 1995;86:248-249. https://doi.org/10.1093/oxfordjournals.jhered.a111573
  9. Rousset F. Genepop'007: a complete re-implementation of the genepop software for Windows and Linux. Mol Ecol Resour 2008;8:103-106. https://doi.org/10.1111/j.1471-8286.2007.01931.x
  10. Zachary AA, Montgomery RA, Leffell MS. Defining unacceptable HLA antigens. Curr Opin Organ Transplant 2008;13:405-410. https://doi.org/10.1097/MOT.0b013e3283071450
  11. Lee KW and Kim YS. Serologic ambiguity and allelic frequency of the HLA-B40 family in the Korean population. Tissue Antigens 1997;49:383-388. https://doi.org/10.1111/j.1399-0039.1997.tb02766.x
  12. Lee KW, Oh DH, Lee C, Yang SY. Allelic and haplotypic diversity of HLAA, -B, -C, -DRB1, and -DQB1 genes in the Korean population. Tissue Antigens 2005;65:437-447. https://doi.org/10.1111/j.1399-0039.2005.00386.x
  13. Kerman R, Lappin J, Kahan B, Katz S, McKissick E, Hosek K, et al. The crossmatch may still be the most clinically relevant histocompatibility test performed. Clin Transpl 2007:227-229.
  14. Kerman RH. Understanding the sensitized patient. Heart Fail Clin 2007; 3:1-9. https://doi.org/10.1016/j.hfc.2007.03.003
  15. Phelan D, Mohanakumar T, Ramachandran S, Jendrisak MD. Living donor renal transplantation in the presence of donor-specific human leukocyte antigen antibody detected by solid-phase assay. Hum Immunol 2009;70:584-588. https://doi.org/10.1016/j.humimm.2009.05.007
  16. Aubert V, Venetz JP, Pantaleo G, Pascual M. Low levels of human leukocyte antigen donor-specific antibodies detected by solid phase assay before transplantation are frequently clinically irrelevant. Hum Immunol 2009;70:580-583. https://doi.org/10.1016/j.humimm.2009.04.011
  17. Ho EK, Vasilescu ER, Colovai AI, Stokes MB, Hallar M, Markowitz GS, et al. Sensitivity, specificity and clinical relevance of different cross-matching assays in deceased-donor renal transplantation. Transpl Immunol 2008;20:61-67. https://doi.org/10.1016/j.trim.2008.09.013
  18. Bray RA, Murphey C, Schaub S. Calculated PRA: a process whose time has come or 'Deja vu' all over again? Am J Transplant 2011;11:650-651. https://doi.org/10.1111/j.1600-6143.2011.03452.x
  19. Vaidya S, Hilson B, Sheldon S, Cano P, Fernandez-Vina M. DP reactive antibody in a zero mismatch renal transplant pair. Hum Immunol 2007; 68:947-949. https://doi.org/10.1016/j.humimm.2007.10.013
  20. Goral S, Prak EL, Kearns J, Bloom RD, Pierce E, Doyle A, et al. Preformed donor-directed anti-HLA-DP antibodies may be an impediment to successful kidney transplantation. Nephrol Dial Transplant 2008;23:390-392.
  21. Bray RA, Nolen JD, Larsen C, Pearson T, Newell KA, Kokko K, et al. Transplanting the highly sensitized patient: The emory algorithm. Am J Transplant 2006;6:2307-2315. https://doi.org/10.1111/j.1600-6143.2006.01521.x
  22. Appel JZ 3rd, Hartwig MG, Cantu E 3rd, Palmer SM, Reinsmoen NL, Davis RD. Role of flow cytometry to define unacceptable HLA antigens in lung transplant recipients with HLA-specific antibodies. Transplantation 2006;81:1049-1057. https://doi.org/10.1097/01.tp.0000204046.89396.c5
  23. Leffell MS, Cherikh WS, Land G, Zachary AA. Improved definition of human leukocyte antigen frequencies among minorities and applicability to estimates of transplant compatibility. Transplantation 2007;83:964-972. https://doi.org/10.1097/01.tp.0000258588.09356.d7

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