Antibody monitoring: a solid approach to predicting clinical outcome.

On March 2 and 3 of this year, a conference on histocompatibility testing was held in Chicago and attended by transplant physicians, transplant surgeons, and histocompatiblity laboratory directors. At the end of the conference, some clinicians expressed concerns about the use of solid phase immunoassays for characterizing and quantifying human leukocyte antigen (HLA)-specific antibodies. The article by Reinsmoen et al. is one of a growing number of articles that should allay such concerns while further elucidating factors relevant to interpreting the results of these tests. As with other recent articles, this article shows that results of solid-phase assays correlate with antibody strength which, in turn, allows prediction of crossmatch results. This is extremely relevant when interfering antibodies, such as therapeutic or auto-antibodies, make meaningful interpretation of cell-based tests impossible or when donor tissue is unavailable. The results presented in the article do show the variability inherent in any immunologic assay. There is substantial overlap in the range of Luminex test values among the different patient groups. However, this variability also occurs in cell-based assays. Note that, in this report, the median channel shift in the flow cytometric crossmatch did not always correlate precisely with the outcome of the cytotoxicity crossmatch. Another example of such a variability is in crossmatch proficiency tests, which often do not yield a high consensus among laboratories. However, the authors make several salient points about the interpretation and use of test results. First, solid-phase antibody assays are very useful for monitoring antibody changes within a patient. Second, the authors note that test result values need to be correlated with the clinical data considering the immunosuppression regimen used at a center. Third, and most important, the authors note that all available data should be used in making clinical predictions and clinical decisions. The data they have used here included that from solid-phase assays, flow cytometric and cytotoxicity crossmatches, and from expanded typing of a donor to reconcile the results of the crossmatch with those of the antibody identity. It has been suggested that laboratories should all use the same antibody testing method and apply uniform value for defining strong and weak antibodies. As clearly elucidated in the article by Reinsmoen et al., test, patient, donor, and treatment protocol factors must all be applied to test interpretation. Correlation with a center’s clinical outcomes and coordination with clinical practice are much more important than uniformity among laboratories on the fine points of test interpretation. Solid-phase immunoassays have been a boon to histocompatibility testing, permitting a speed, sensitivity, and specificity in antibody identification that was not possible before. The article by Reinsmoen et al. highlights the very important way in which data generated from solid phase immunoassays of HLA-specific antibody can be used to increase access to transplantation and improve outcomes among patients undergoing desensitization. However, the impact is much more far reaching, as the principles demonstrated here should be applied to all patients who are sensitized before transplantation or develop HLA-specific antibodies afterward. Immunogenetics Laboratory, Johns Hopkins University School of Medicine, Baltimore, MD. Address correspondence to: Andrea A. Zachary, Ph.D., D(ABHI), Immunogenetics Laboratory, Johns Hopkins University School of Medicine, 2041 E, Monument Street, Baltimore, MD 21205. E-mail: aaz@jhmi.edu Received 13 June 2008. Accepted 13 June 2008. Copyright © 2008 by Lippincott Williams & Wilkins ISSN 0041-1337/08/8606-768 DOI: 10.1097/TP.0b013e3181856ffa