*Purpose: The role of non-HLA antibodies (Ab) in HLA-DSA negative antibody mediated rejection (AMR) following heart transplant (HTx) remains largely unknown.

*Methods: Retrospective analysis of all HTx patients at a single center who were admitted for HLA-DSA negative ABMR and had positive non-HLA Ab at time of hospitalization.

*Results: A total of 6 patients were identified (50% female, 83% NICM). Pre-transplant HLA DSA and virtual crossmatch (VXM) were negative in 5 patients. One patient was positive for DR16 DSA at time of transplant with negative flow crossmatch. All presented with severely reduced ejection fraction (EF) at a median of 2.5 years post-transplant. Only one of the 5 biopsies were positive revealing pAMR1. Non- HLA Abs were detected in all patients. Four were positive for AT1R and ETAR Ab, 1 for EC2/EC3 Ab and 1 for MICA Ab. Fifty percent of patients had medication non-compliance or immunosuppression changes prior to presentation. All were treated with steroids. Plasmapheresis and IVIG were used in 2 patients. EF recovered back to baseline in all patients prior to discharge.

Non-HLA Abs remained positive in all patients. One patient with AT1R Ab was treated with an angiotension receptor blocker (ARB). One required photopheresis for persistent heart failure symptoms. In the remaining 4 patients, despite positive non-HLA DSA Ab persisting for least one-year, no further changes in management occurred except continued surveillance given lack of symptoms.

*Conclusions: Non-HLA antibodies should be checked when HLA-DSAs are negative and there is concern for AMR. Treatment options can include steroids, plasmapheresis, IVIG, ARB and/or surveillance. Further investigation is needed in the field of non-HLA Ab, particularly in long term management and outcomes.

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