Comparison between enzyme-linked immunosorbent assay and cytotoxic cross-match procedures for detecting IgG anti-donor antibodies

Background. Disadvantages inherent to complement-dependent cytotoxicity cro ss-match (CDC XM) methods are the requirements for complement and viable ta rget cells, detection of antibodies (Abs) against non-HLA antigens, and sub jective scoring. Cross-Stat(R) (SangStat Medical Corp., Menlo Park, CA), a recently developed enzyme-linked immunosorbent assay XM procedure for the d etection of IgG; antidonor HLA Abs, is theoretically devoid of these flaws. Methods. We compared results of Cross-Stat and our standard anti-human glob ulin (AHG)-enhanced CDC XM procedure on 524 sera from 230 transplant candid ates, which were evaluated against 51 cadaveric donors, Results. There was a significant correlation between AHG-CDC IgG XM and Cro ss-Stat results (P<0.001). For false negative sera, repeat AHG-CDC IgG XMs were still positive after platelet absorption, indicating that the Abs pres ent were either non-HLA Abs or anti-HLA class II. Flow cytometry testing of false positive sera usually (42/62) substantiated Cross-Stat results, indi cating that the discrepancy with AHG-CDC IgG XM is caused by greater sensit ivity of Cross-Stat, Relative to the AHG-CDC XM, the sensitivity of Cross-S tat was 100%, the specificity was 93%, the positive predictive value was 73 %, and the negative predictive value was 100%, A technical shortcoming of t he Cross-Stat assay is that the frequency of indeterminate samples in the a ssays was 15%, Among 49 Cross-Stat negative vs. 13 Cross-Stat positive prim ary cadaveric renal allograft recipients tall AHG-CDC IgG-XM negative), the re was no statistical difference in overall graft survival. Conclusion. Given the important theoretical advantages of enzyme-linked imm unosorbent assay-based XM methods over the CDC XM, however, further testing of the clinical relevance of the Cross-Stat is warranted.