Abstract

Purpose: Pre-formed HLA antibodies have historically been detected by complement dependent cytotoxicity (CDC) assays. The introduction of Luminex assays to detect HLA antibodies has resulted in increased detection of sensitisation, however, the clinical impact of Luminex detected HLA antibodies is unclear. The purpose of this study has been to analyse pre-transplant Luminex detected HLA antibodies, their ability to fix human C4d and to determine the effect on lung allograft survival. Methods and Materials: Pre-transplant serum from 394 lung transplant patients (144 Heart-Lung, 103 Double Lung and 147 Single Lung) was retrospectively tested for the presence of HLA antibodies using Labscreen (One Lambda) and Lifematch (Tepnel) Luminex assays. All sera had previously been screened by CDC at the time of transplant. C4d deposition on HLA coated Luminex beads was also measured. Results were analysed and correlated with graft survival using Kaplan-Meier and Logrank statistics. Results: Prior to transplantation 6 patients had produced HLA antibodies by CDC, all of which were donor specific (DSA). The Luminex assays detected HLA antibodies in a further 50 patients, 16 of which were donor specific. The one year actuarial graft survival for CDC ve DSA patients (n 6) was 0% compared to 56.3% for Luminex ve DSA (n 16), 82.4% for Luminex non-donor specific (n 34) and 71% for Negative patients (n ), p 0.0001. Ten % of the luminex positive sera (44 tested to date) fixed C4d. The one year graft survival for C4d ve/DSA (n 4) was 0%, C4d-ve DSA ve (n 12) 50%, C4d-ve DSA-ve (n 28) 78.6%, compared with 71% for antibody negative patients(p 0.0004). Conclusions: Detection of Luminex ve donor specific HLA antibodies is a prognostic indicator for poor graft survival. The development of a technique to detect C4d fixing donor specific Luminex detected antibodies may be a useful tool to identify patients at high risk of accelerated graft failure.

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