Interpreting Anti-HLA Antibody Testing Data: A Practical Guide for Physicians

Overview

Journal Transplantation

Specialty General Surgery

Date 2016 May 4

PMID 27140516

Citations 19

Authors

Carrie A Schinstock

Manish J Gandhi

Mark D Stegall

Affiliations

Soon will be listed here.

Abstract

The development of sensitive methods for alloantibody detection has been a significant advance in clinical transplantation. However, the complexity of the data from solid phase and crossmatch assays has led to potential confusion about how to use the results for clinical decision making. The goal of this review is to provide a practical guide for transplant physicians for the interpretation of antibody data to supplement consultation with local tissue typing experts. Sources of variability in both the solid phase and crossmatch assay are discussed as are recent data regarding C1q binding antibodies and IgG subclass testing. Although definitive approaches to alloantibody testing are not possible with our current knowledge, we outline a pragmatic approach that we hope will enhance clinical management in this area.

Citing Articles

Crossmatch assays in transplantation: Physical or virtual?: A review.

Rocha Y, Jaramillo A, Neumann J, Hacke K, Palou E, Torres J Medicine (Baltimore). 2023; 102(50):e36527.

PMID: 38115324 PMC: 10727546. DOI: 10.1097/MD.0000000000036527.

Impact of Resolved Preformed, Persistent Preformed, and De Novo Anti-HLA Donor-Specific Antibodies in Kidney Transplant Recipients on Long-Term Renal Graft Outcomes.

Gniewkiewicz M, Czerwinska K, Zielniok K, Durlik M J Clin Med. 2023; 12(10).

PMID: 37240467 PMC: 10219016. DOI: 10.3390/jcm12103361.

Donor specific antibody surveillance among pediatric kidney transplant programs: A report from the improving renal outcome collaborative.

Steinbach E, Barletta G, Patel H, Hooper D, Garro R, Harshman L Pediatr Transplant. 2023; 27(3):e14498.

PMID: 36898856 PMC: 10305844. DOI: 10.1111/petr.14498.

The detrimental effect of donor-specific antibodies is irrespective of its level in highly-immunized living donor kidney transplant recipients: A case-control series.

Tramper T, Roelen D, Brand-Schaaf S, Kal-van Gestel J, Kho M, Reinders M Front Immunol. 2023; 13:1093359.

PMID: 36703958 PMC: 9873371. DOI: 10.3389/fimmu.2022.1093359.

Rapid desensitization through immunoadsorption during cardiopulmonary bypass. A novel method to facilitate human leukocyte antigen incompatible heart transplantation.

Issitt R, Cudworth E, Cortina-Borja M, Gupta A, Kallon D, Crook R Perfusion. 2023; 39(3):543-554.

PMID: 36625378 PMC: 10943618. DOI: 10.1177/02676591221151035.

References

Stegall M, Chedid M, Cornell L . The role of complement in antibody-mediated rejection in kidney transplantation. Nat Rev Nephrol. 2012; 8(11):670-8. DOI: 10.1038/nrneph.2012.212. View

Sigdel T, Sarwal M . Moving beyond HLA: a review of nHLA antibodies in organ transplantation. Hum Immunol. 2013; 74(11):1486-90. PMC: 5221517. DOI: 10.1016/j.humimm.2013.07.001. View

Gebel H, Bray R . HLA antibody detection with solid phase assays: great expectations or expectations too great?. Am J Transplant. 2014; 14(9):1964-75. DOI: 10.1111/ajt.12807. View

Zeevi A, Lunz J, Feingold B, Shullo M, Bermudez C, Teuteberg J . Persistent strong anti-HLA antibody at high titer is complement binding and associated with increased risk of antibody-mediated rejection in heart transplant recipients. J Heart Lung Transplant. 2012; 32(1):98-105. PMC: 3628631. DOI: 10.1016/j.healun.2012.09.021. View

Hidalgo L, Campbell P, Sis B, Einecke G, Mengel M, Chang J . De novo donor-specific antibody at the time of kidney transplant biopsy associates with microvascular pathology and late graft failure. Am J Transplant. 2009; 9(11):2532-41. DOI: 10.1111/j.1600-6143.2009.02800.x. View

Glotz D, Lucchiari N, Pegaz-Fiornet B, Suberbielle-Boissel C . Endothelial cells as targets of allograft rejection. Transplantation. 2006; 82(1 Suppl):S19-21. DOI: 10.1097/01.tp.0000231348.55262.5a. View

Zachary A, Lucas D, Detrick B, Leffell M . Naturally occurring interference in Luminex assays for HLA-specific antibodies: characteristics and resolution. Hum Immunol. 2009; 70(7):496-501. DOI: 10.1016/j.humimm.2009.04.001. View

Sicard A, Ducreux S, Rabeyrin M, Couzi L, McGregor B, Badet L . Detection of C3d-binding donor-specific anti-HLA antibodies at diagnosis of humoral rejection predicts renal graft loss. J Am Soc Nephrol. 2014; 26(2):457-67. PMC: 4310653. DOI: 10.1681/ASN.2013101144. View

Jackson A, Lucas D, Melancon J, Desai N . Clinical relevance and IgG subclass determination of non-HLA antibodies identified using endothelial cell precursors isolated from donor blood. Transplantation. 2011; 92(1):54-60. DOI: 10.1097/TP.0b013e31821b60e9. View

10.

Pereira S, Perkins S, Lee J, Shumway W, LeFor W, Lopez-Cepero M . Donor-specific antibody against denatured HLA-A1: clinically nonsignificant?. Hum Immunol. 2011; 72(6):492-8. DOI: 10.1016/j.humimm.2011.02.012. View

11.

Terasaki P, Ozawa M, Castro R . Four-year follow-up of a prospective trial of HLA and MICA antibodies on kidney graft survival. Am J Transplant. 2007; 7(2):408-15. DOI: 10.1111/j.1600-6143.2006.01644.x. View

12.

Gandhi M, Carrick D, Jenkins S, De Goey S, Ploeger N, Wilson G . Lot-to-lot variability in HLA antibody screening using a multiplexed bead-based assay. Transfusion. 2013; 53(9):1940-7. PMC: 3626740. DOI: 10.1111/trf.12064. View

13.

Valenzuela N, Reed E . Antibodies in transplantation: the effects of HLA and non-HLA antibody binding and mechanisms of injury. Methods Mol Biol. 2013; 1034:41-70. PMC: 3879955. DOI: 10.1007/978-1-62703-493-7_2. View

14.

Mizutani K, Terasaki P, Rosen A, Esquenazi V, Miller J, Shih R . Serial ten-year follow-up of HLA and MICA antibody production prior to kidney graft failure. Am J Transplant. 2005; 5(9):2265-72. DOI: 10.1111/j.1600-6143.2005.01016.x. View

15.

Grafft C, Cornell L, Gloor J, Cosio F, Gandhi M, Dean P . Antibody-mediated rejection following transplantation from an HLA-identical sibling. Nephrol Dial Transplant. 2009; 25(1):307-10. DOI: 10.1093/ndt/gfp526. View

16.

Montgomery R, Lonze B, King K, Kraus E, Kucirka L, Locke J . Desensitization in HLA-incompatible kidney recipients and survival. N Engl J Med. 2011; 365(4):318-26. DOI: 10.1056/NEJMoa1012376. View

17.

Jacob E, De Goey S, Gandhi M . Positive virtual crossmatch with negative flow crossmatch results in two cases. Transpl Immunol. 2011; 25(1):77-81. DOI: 10.1016/j.trim.2011.05.007. View

18.

Le Bas-Bernardet S, Hourmant M, Valentin N, Paitier C, Giral-Classe M, Curry S . Identification of the antibodies involved in B-cell crossmatch positivity in renal transplantation. Transplantation. 2003; 75(4):477-82. DOI: 10.1097/01.TP.0000047311.77702.59. View

19.

Kaneku H, OLeary J, Taniguchi M, Susskind B, Terasaki P, Klintmalm G . Donor-specific human leukocyte antigen antibodies of the immunoglobulin G3 subclass are associated with chronic rejection and graft loss after liver transplantation. Liver Transpl. 2012; 18(8):984-92. DOI: 10.1002/lt.23451. View

20.

OLeary J, Klintmalm G . Impact of donor-specific antibodies on results of liver transplantation. Curr Opin Organ Transplant. 2013; 18(3):279-84. DOI: 10.1097/MOT.0b013e3283614a10. View