Gandhi MJ, Degoey S, Falbo D, et al. High levels of anti-HLA antibody with strong affinity and avidity can saturate the solid phase platform or interfere with alloantibody binding to the beads leading to SAB results that are lower than expected for a particular antigenic specificity.
However, if the solid phase assay is positive suggesting the presence of alloantibody, further evaluation is necessary. Mizutani K, Terasaki P, Rosen A, et al. Antibodies against MICA antigens and kidney-transplant rejection. Kaneku H, O'Leary JG, Taniguchi M, et al. Thank you! 50.
For transplant candidates awaiting a deceased donor, the goal is to optimize access to transplantation while avoiding an unexpected final XM. 54.
47. 55. The MFI threshold to distinguish negative and positive also depends on a particular center’s risk tolerance for AMR and clinical context. Schinstock, Carrie A. MD; Gandhi, Manish J. MD; Stegall, Mark D. MD. The current fluorescent-based solid phase assay is able to concurrently distinguish up to 100 different microparticles or beads. 42. Interpretation of HLA single antigen bead assays.
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When the HLA antigen is attached to the bead, ... That being said, if a sensitized patient has AMR without detectable anti-HLA DSA, testing for non-HLA antibodies using the few commercially available assays is a consideration. Schinstock C, Cosio F, Cornell L, et al. helped with the design of the work and critical revision. Emerging evidence suggests that DSA of the IgG 3 subclass is particularly deleterious to the renal and liver allografts.54,66-72 However, studies of IgG subclasses in transplantation are limited because few groups have examined complete IgG subclass characterization [IgG1-IgG4] serially. Our personal recommendation is to perform only one serum dilution in highly sensitized patients at baseline and as needed to detect prozone. C1q single antigen bead assay only detects high titer/avidity class-I anti HLA antibodies detected by single antigen beads. This paper provides transplant physicians approaches to understanding this changing field. Low expression of HLA Cw and DP is very common, but occasionally other HLA antigens have low expression.20 Although the risk to undergo transplantation is generally low, it is unclear whether the HLA expression could change during an inflammatory event, for example. Jackson AM, Sigdel TK, Delville M, et al.
Naturally occurring interference in Luminex assays for HLA-specific antibodies: characteristics and resolution. 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.
If the auto-flow XM is positive, and you have confirmed that the patient has not had any recent sensitization and the donor typing is complete, you can proceed to transplant. Although it is advantageous to completely avoid DSA, it is not always possible given a patient’s sensitization. Chen G, Sequeira F, Tyan DB. HLA testing is performed and test results are kept on file to compare with results from those people who need a donor match. These patients usually require no further investigation. Hidalgo LG, Campbell PM, Sis B, et al. 62. 7. 70. Burns JM, Cornell LD, Perry DK, et al. HLA antibody detection with solid phase assays: great expectations or expectations too great? No special preparation is needed for either method. If you … Alloantibody can bind a shared epitope on multiple antigens resulting in the positivity of more than one bead.19,32-34 The strength of this antibody would be diluted and underrepresent its clinical importance if the donor cell only has one of these antigens. Woodle ES, Shields AR, Ejaz NS, et al. Greater consistency in candidate and deceased donor HLA typing requirements across organ types.
67. We recognize that further serum dilution is needed to obtain the antibody titer, which is optimal to determine the level of antibody. 61. Despite improvements in patient selection and management, every transplant carries some risk of graft loss. 29. Does anyone understand how to interpret the HLA-DR test results from Labcorp? The clinical significance of antibodies to human vascular endothelial cells after cardiac transplantation. Inter and intra laboratory concordance of HLA antibody results obtained by single antigen bead based assay. External substances (IgM antibody,26 intravenous immunoglobulin, antithymocyte globulin,27 immune complexes, complement,28,29 or nonspecific binding of external substances) can also interfere with antibody binding to the bead or the secondary detection agent and also lead to this phenomenon.30,31 This effect does not necessarily affect all antigen specificities for a particular patient at one time and is mainly a consideration for highly sensitized patients (cPRA >80%). 59.
44. 40. You may be trying to access this site from a secured browser on the server. Otten HG, Verhaar MC, Borst HP, et al. The XM9-11 is considered the final test to determine the safety of moving forward with transplantation, but now sensitive SAB assays have made the virtual crossmatch possible. This MFI cutoff also differs depending on the organ to be transplanted. 4. Get new journal Tables of Contents sent right to your email inbox, August 2016 - Volume 100 - Issue 8 - p 1619-1628, https://optn.transplant.hrsa.gov/PublicComment/pubcommentPropSub_335.pdf, http://www.atcmeetingabstracts.com/abstract/donor-specific-alloantibody-after-positive-crossmatch-kidney-transplantation-with-eculizumab-ec-correlation-with-transplant-glomerulopathy-and-graft-failure/, Interpreting Anti-HLA Antibody Testing Data: A Practical Guide for Physicians, Articles in PubMed by Carrie A. Schinstock, MD, Articles in Google Scholar by Carrie A. Schinstock, MD, Other articles in this journal by Carrie A. Schinstock, MD, A 2018 Reference Guide to the Banff Classification of Renal Allograft Pathology, Consensus Guidelines on the Testing and Clinical Management Issues Associated With HLA and Non-HLA Antibodies in Transplantation, Patient's Death with a Functioning Graft is still the Most Common Cause of Kidney Transplant Loss, Subclinical Antibody-mediated Rejection After Kidney Transplantation: Treatment Outcomes, A Practical Guide to the Clinical Implementation of Biomarkers for Subclinical Rejection Following Kidney Transplantation. Although ideally all DSA would be avoided, it is not always possible. 53.
While making the final diagnosis, all test results … Deciphering complement interference in anti-human leukocyte antigen antibody detection with flow beads assays. Even if donor HLA is expressed, sometimes DSA is of low enough affinity and avidity that it does not produce a positive flow XM. Visentin J, Guidicelli G, Bachelet T, et al. This might include relatives of someone needing a transplant.
69.
Although there are no readily available tests to determine HLA expression on the intended donor cells, occasionally a XM can be done with a surrogate donor (a different donor with same HLA), which would be positive. We also provide possible explanations for ambiguous test results and recommendations for further investigation.
26. U.S. Department of Health & Human Services. † Refer to.
33. If the multi-antigen beads used for screening are positive, we suggest doing SABs to precisely identify the HLA antigen to which the patient has alloantibody. Regardless of the strength of alloantibody, without an antigenic target, the risk of AMR is generally low. Consideration of the underlying clinical context is also critical.
Although beyond the scope of this article, it is also always important to have a protocol to manage AMR because AMR can unexpectedly occur even in presumably low-risk situations.
To minimize the risk of AMR many transplant centers avoid HLA antigens to which the patient has been previously exposed or has had historical alloantibody. 57. Visentin J, Vigata M, Daburon S, et al. Moving beyond HLA: a review of nHLA antibodies in organ transplantation. Practical value of identifying antibodies to cryptic HLA epitopes in cardiac transplantation.
But there are also high-risk situations that are not as apparent when looking at SAB tests alone (Table 1). If your blood does contain the HLA antibodies (a positive test result), you will receive a letter in the mail. Desensitization in HLA-incompatible kidney recipients and survival. Tambur AR, Herrera ND, Haarberg KM, et al. This is referred as the prozone or hook effect. The SAB assay is only semiquantitative, and the variation in MFI has been reported as high as 62%, especially when the MFI is relatively low (1000-3000).18. The antibody titer is determined by doing serial dilutions. Again, if the solid phase assay is completely negative, the risk for AMR is low, and the XM does not add considerably to the evaluation. Usually all XM testing is negative, and transplantation can proceed.
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