Malte Ziemann (Lübeck / DE), Monika Lindemann (Essen / DE), Michael Hallensleben (Hannover / DE), Wolfgang Altermann (Halle / DE), Karina Althaus (Tübingen / DE), Klemens Budde (Berlin / DE), Gunilla Einecke (Hannover / DE), Ute Eisenberger (Essen / DE), Andrea Ender (Stuttgart / DE), Thorsten Feldkamp (Kiel / DE), Florian Grahammer (Hamburg / DE), Martina Guthoff (Tübingen / DE), Christopher Holzmann-Littig (München / DE), Christian Hugo (Dresden / DE), Teresa Kauke (München / DE), Stephan Kemmner (München / DE), Martina Koch (Hamburg / DE; Mainz / DE), Nils Lachmann (Berlin / DE), Matthias Marget (Hamburg / DE), Christian Morath (Heidelberg / DE), Martin Nitschke (Lübeck / DE), Lujtz Renders (München / DE), Sabine Scherer (Heidelberg / DE), Julian Stumpf (Dresden / DE), Vedat Schwenger (Stuttgart / DE), Florian Sommer (Augsburg / DE), Bernd M. Spriewald (Erlangen / DE), Caner Süsal (Heidelberg / DE; Istanbul / TR), Daniel Zecher (Regensburg / DE), Murielle Verboom (Hannover / DE), Falko M. Heinemann (Essen / DE)
Single antigen (SA) tests are indispensable for HLA antibody identification. 3 tests are available, but little is known about their comparative prognostic value.
Sera from kidney transplant patients with preformed donor-specific antibodies (DSA) were selected from a multicenter study. All 49 sera with sufficient aliquots were tested by a microspot SA test from BAG and bead array SA assays from Immucor/Werfen (IMM) and ThermoFisher/OneLambda (OLI). ABMR-free survival within 6 months posttransplant and 10-year death-censored graft survival (10yGS) were evaluated according to (1) number of SA tests classifying the serum as DSA-positive (DSA+), and (2) number of SA tests detecting at least 1 identical DSA specificity.
(1) 22 sera were DSA+ by all tests and had highest incidence of ABMR and lowest 10yGS. The OLI assay was most sensitive and classified all sera as DSA+, that were DSA+ by BAG and/or IMM. It was the only test detecting DSA in 13 sera which were DSA-negative (DSA-) by both BAG and IMM; however, these patients had similar ABMR-free survival and 10yGS as patients without any DSA. Overall, BAG and IMM seemed to have comparable sensitivity: 8 sera were DSA+ by BAG and OLI, and 4 sera DSA+ by IMM and OLI. Additional review of SA results revealed that some OLI results had been influenced by false positive reactions due to denatured beads or high background, while some weak reactions in the BAG test had been missed in standard evaluation. Correction of these misinterpretations did not significantly change the above-mentioned results. (2) In 18 sera, at least 1 DSA was detected by all tests. These patients had significantly more ABMR and worse 10yGS. In 15 sera, the same DSA was detected by IMM and OLI, or by BAG and OLI, respectively. These patients had significantly more ABMR, but no significant difference in 10yGS. In 22 sera, DSA were detectable by 1 or more tests, but no specificity was positive in more than 1 assay (in all 22 sera DSA were detected by OLI, in 1 additionally another DSA by IMM, and in 2 another DSA by BAG). Incidence of ABMR and graft survival were similar to DSA- patients.
OLI was the most sensitive assay but was also prone to false positive results. While false positive reactions were rare for BAG and IMM, these tests missed some DSA associated with an increased risk for ABMR. Larger studies are necessary to confirm these results.
The study was supported by free reagents provided by the companies BAG, Immucor and OneLambda/ThermoFisher.