The Effects of Donor-Specific Antibody Characteristics on Cardiac Allograft Vasculopathy.

Cardiac allograft vasculopathy (CAV) is a major cause of late graft dysfunction and mortality after heart transplantation. The pathophysiology of CAV consists of a complex interplay between donor risk factors, recipient comorbidities, and immune-mediated processes. Despite many studies showing a correlation between donor-specific antibodies (DSA) and CAV, the effects of different DSA types on the severity of CAV remains elusive. This study investigates the characteristics of DSA amongst different CAV severity groups. We evaluated 526 adult heart transplant recipients at a single tertiary medical center between January 2010 and August 2015. Subjects were screened for DSA at the time of transplant, 1 month, 3 months, 6 months, 1 year, and then annually thereafter. CAV screening was performed with annual angiography. Subjects were divided into those with DSA (n= 143) and those without DSA (control group, n =383). Subjects with DSA were further categorized into those with persistent DSA (n=34), transient DSA (n=106), 1:8 dilution positive DSA (n=45), complement-binding (C1q) DSA (n=36), Class I DSA (n=36), and Class II DSA (n=106). The mean duration of follow up was 3.6 years. The outcomes are the incidence of CAV based on the ISHLT grading scale. Subjects with persistent DSA were found to have higher incidence of moderate-to-severe CAV (CAV2/3) compared the control group (p = <0.001). On the contrary, there was no difference in the incidence of CAV2/3 between subjects with transient DSA and the control group (p =0.873). Subjects with 1:8 dilution positive DSA and C1q positive DSA also had a higher incidence of CAV2/3 when compared those without DSA (p =0.001, p =<0.001). Between subjects with Class I and Class II DSA, only subjects with Class II DSA had higher incidence of CAV 2/3 compared to the control group (p =0.042). DSA that are persistent, 1:8 dilution positive, C1q positive, and Class II are associated with more severe grades of CAV. Given CAV2/3 is linked with higher mortality post-transplantation, these DSA characteristics may serve as prognostic markers of disease and may warrant consideration for treatment. [ABSTRACT FROM AUTHOR]