Comparison of two donor‐derived cell‐free DNA tests and a blood gene‐expression profile test in heart transplantation

Abstract

Background Donor‐derived cell‐free DNA (dd‐cfDNA) testing is an emerging screening modality for noninvasive detection of acute rejection (AR). This study compared the testing accuracy for AR of two commercially available dd‐cfDNA and gene‐expression profiling (GEP) testing in heart transplant (HTx) recipients. Methods This is a retrospective, observational study of HTx only patients who underwent standard and expanded single nucleotide polymorphism (SNP) dd‐cfDNA between October 2020 to January 2022. Comparison with GEP was also performed. Assays were compared for correlation, accurate classification, and prediction for AR. Results A total of 428 samples from 112 unique HTx patients were used for the study. A positive standard SNP correlated with the expanded SNP assay (p < .001). Both standard and expanded SNP tests showed low sensitivity (39%, p = 1.0) but high specificity (82% and 84%, p = 1.0) for AR. GEP did not improve sensitivity and showed worse specificity (p < .001) compared to standard dd‐cfDNA. Conclusion We found no significant difference between standard and expanded SNP assays in detecting AR. We show improved specificity without change in sensitivity using dd‐cfDNA in place of GEP testing. Prospective controlled studies to address how to best implement dd‐cfDNA testing into clinical practice are needed.

Donor-Specific Antibody Testing is an Effective Surveillance Strategy for High-Risk Antibody Mediated Rejection in Heart Transplant Patients in the Contemporary Era

“…The primary reason for transplantation was non-ischemic cardiomyopathy (60%). Highly sensitized (panel of reactive antibodies >= 10%) 29 patients comprised 19% of the study cohort. Induction therapy was used in 246 patients (47%) and 73 patients (13%) underwent multi-organ transplants.…”

“…The typical EMB surveillance protocol at the University of California, San Diego Health (UC San Diego Health) has been described previously. 16 This protocol includes C4d immunofluorescence at 2 and 4 weeks, and at 3, 6 and 12 months during surveillance EMBs in addition to for-cause EMB indication. 2,3 DSA testing is also performed at the same time intervals for surveillance indication and whenever there is clinical concern for AMR.…”

“…The primary reason for transplantation was non-ischemic cardiomyopathy (60%). Highly sensitized (panel of reactive antibodies >= 10%) 29 patients comprised 19% of the study cohort.…”

Incidence of Acute Rejection Compared With Endomyocardial Biopsy Complications for Heart Transplant Patients in the Contemporary Era

“…Typical induction and AR treatment protocols for UC San Diego Health has been described previously. 19 …”

“… 3 At UC San Diego Health, a weekly pathological review of all EMB samples is performed as previously described. 19 Treatment for AR refers to a significant change in a subject’s immunomodulatory regimen including: initiation or increase in corticosteroids to a prednisone equivalent of 40 mg/d or higher, intravenous immune globulin, plasmapheresis, rituximab, thymoglobulin, and/or bortezomib use.…”