Abstract

Purpose Solid phase assays detect anti-HLA antibodies with high accuracy and sensitivity, however debate continues on how these results should be interpreted in the setting of lung transplantation. Methods and Materials We performed a retrospective analysis of pre-transplant anti-HLA antibody levels detected using a solid-phase HLA microbead assay (Luminex) in 80 patients undergoing lung transplantation at a single centre between 1/1/09 and 1/5/10. All patients underwent prospective T- and B-cell crossmatches (complement-dependent cytotoxicity assays) prior to transplantation. Outcome variables analyzed included acute cellular and antibody-mediated rejection, BOS and survival. Results Pre-transplant class I and class II anti-HLA antibodies were present in 31/80 (38%) and 13/80 (10%) patients, respectively, but did not predict a positive T- or B-cell crossmatch which was weekly positive in 1/80 and 14/80 patients, respectively. HLA class I and II donor-specific antibodies (DSA) were present pre-transplant in 13 and 7 patients, respectively. The presence pre-transplant of class I DSA, irrespective of a negative prospective T- and B-cell crossmatch predicted for a poor outcome (Odds ratio for BOS/death 4.6, p = 0.03). Pre-transplant DSA was not associated with the subsequent development of either acute cellular or antibody-mediated rejection. Only two patients developed clinically significant antibody-mediated rejection. Both developed DSA following transplant having not been present pre-transplant. Conclusions Identifying DSA pre-transplant predicts poor outcomes post-transplant and provides prognostic information beyond that which has been historically provided by a negative prospective crossmatch. Future studies need to focus on defining the level of pre-transplant DSA as measured using solid phase assays that predict for adverse outcomes following lung transplantation.

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