*Purpose: Antibody-mediated rejection (AMR) is defined by pathologic evaluation of endomyocardial biopsy (EMB) for both histologic and immunopathologic components. Detectable donor specific antibodies (DSAs) in the setting of acute AMR are not always present. This may be related to variable interpretations of AMR by pathologists. The INTERHEART study evaluated for mRNA transcripts via the molecular microscope (MMDx) to assess for T cell-mediated (TCMR) and antibody-mediated (ABMR) rejection. We retrospectively evaluated the presence of detectable DSA in heart transplant (HTx) recipients with AMR as compared to those with ABMR by MMDx.

*Methods: Between 2016 and 2018, 72 HTx EMB samples were evaluated by pathology and MMDx. Significant DSA was defined as detectable within 1 month of EMB with mean fluorescence intensity (MFI) greater than 5,000.

*Results: In HTx recipients with AMR grade 1 or greater (n=17), 35.3% of patients had DSA as compared to patients with no evidence of AMR (n=50), 14% had DSA (p=NS). Conversely, in patients with abnormal MMDx concerning for ABMR (n=18), 44.4% of patients had DSA as compared to those with normal MMDx (n=44), 4.5% of patients had DSA (p<0.05). (Figure)

*Conclusions: In this small study of HTx recipients who undergo EMB for evaluation of rejection, patients with abnormal MMDx concerning for ABMR have a greater prevalence of detectable DSA greater than MFI of 5,000 as compared to those with normal MMDx. In patients with abnormal histology concerning for AMR, there is no detectable difference in DSA as compared to pathology interpretation as normal. The MMDx system may have a greater relationship with detectable DSA than histology interpretation for AMR and future studies should be conducted given the relationship of DSA to adverse outcomes.

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