A role for flow-PRA monitoring following cardiac allograft transplantation

The clinical significance of circulating HLA antibodies post heart transplantation (HT) is an area of on-going debate. In the current study evaluated 52 HT recipient utilizing Flow cytometry as the most sensitive and specific technique to detect HLA class I and II antibodies. The patient demographics were as follows: age 47 ± 13 yrs, 84% male, 35% African American, ischemia time 181 ± 51 mins. Treatment included triple immunosuppression without anti-lymphocyte antibodies. Of these patients, 56% had L-VAD implanted prior to transplantation. Serum specimens were collected at fixed intervals [2,4 weeks; 2,3,6 and 12 month post HT]. Flow PRA analysis was performed using microparticles coated with either class I or class II HLA antigens. Allograft biopsies were evaluated using ISHLT score criteria. During the first year post HT 22 recipients expressed HLA antibodies (16 of whom had only class I antibodies, and 9 had only class II antibodies). Interestingly, 3 of these patients expressed HLA antibodies only transiently (between 2-6 months post HT). Four patients had detectable HLA antibodies in the early post HT period that disappeared after 2-6 months. Conversely, two patients had detectable HLA antibodies only at a later period post HT. A significant association was observed between the level of donor-recipient HLA-A mismatches and the presence of HLA class I antibodies (80% of patients with class I antibodies had 2 mismatches at the HLA-A locus, p=0.036). Mismatches at the B or DR loci were not associated with class I or II PRA, respectively. In our cohort of patients, a significant association was observed between severity of rejection episodes (ISHLT score of 3) and the presence of class I PRA. In contrast, no such correlation was observed with recipients positive for class II PRA. A trend toward significance was noted among patients who had L-VAD prior to transplantation and the presence of post transplant class I PRA (p=0.063), but not class II PRA (p=0.14). we thus conclude that 1) Mismatches at HLA-A (but not in HLA-B) locus are associated with the presence of class I PRA post HT, and, 2) Recipients with class I antibodies have more severe rejection episodes. We are currently in the process of evaluating the role of HLA antibodies vascular rejection, and in particular in allograft intimal thickening, as measured by intra-vascular ultrasound imaging (IVUS).