Noninvasive discrimination of rejection in cardiac allograft recipients using gene expression profiling

摘要: Rejection diagnosis by endomyocardial biopsy (EMB) is invasive, expensive and variable. We investigated gene expression profiling of peripheral blood mononuclear cells (PBMC) to discriminate ISHLT grade 0 rejection (quiescence) from moderate/severe (ISHLT ≥3A). Patients were followed prospectively with sampling at post-transplant visits. Biopsies graded criteria locally three independent pathologists blinded clinical data. Known alloimmune pathways leukocyte microarrays identified 252 candidate genes for which real-time PCR assays developed. An 11 test was derived a training set (n = 145 samples, 107 patients) using linear discriminant analysis (LDA), converted into score (0–40), validated in an 63 patients). The distinguished biopsy-defined quiescence (p 0.0018) the validation set, had agreement 84% (95% CI 66% C94%) ≥3A rejection. >1 year scores below 30 (approximately 68% study population) are very unlikely have (NPV 99.6%). Gene testing can detect absence rejection, thus avoiding certain settings. Additional experience needed establish role molecular event prediction immunosuppression management.