Predictive Value of HLA Antibody Characteristics in Progression of Subclinical Antibody Mediated Rejection in Heart Transplant Recipients

Abstract

Purpose Donor specific antibody (DSA) is a risk factor for antibody-mediated rejection (AMR). Concomitant detection of C4d & C3d in heart biopsies correlates with DSA and allograft dysfunction. Detection of C4d only in surveillance biopsies may not be associated with allograft dysfunction. However, conversion from C4d only to C4d + C3d is noted in ~20% of cases (C4d converters). We studied DSA patterns in clinical (C4d+C3d+ & C4d converters) & subclinical (C4d+) AMR. Methods and Materials Of 1589 transplants, 610 were screened for AMR (last 6 yr). We studied DSA patterns in C4d+ asymptomatic patients, C4d+C3d+ biopsies symptomatic patients & patients who started as C4d+ & converted to C4d+C3d+. We also compared cPRA & crossmatches. Results Significant differences in DSA incidence, mean cPRA, & DSA mean MFI were noted across all groups with C4d+ patients having the lowest values ( table 1 ). DSA mean MFI was significantly higher in patients with clinical AMR ( table 1 ). C4d converters had significantly higher mean cPRA & DSA, driven by higher DQ DSA but not class I DSA compared to patients who remained C4d+ ( Table 2 ). Having any DSA, DQ DSA or cPRA≥50% at time of biopsy was associated with C4d conversion with high -ve predictive value (NPV) but low +ve predictive value (PPV). Conclusions Our data suggest that HLA antibody characteristics may be relevant in determining which subclinical C4d+ may not progress to clinical AMR & warrants investigation in larger cohorts. Table 1 Any DSA DSA Cl I DSA Cl II DSA Cl I +II mean ± SE cPRA mean ± SE MFI C4d+: n=34 19, 56% 9, 26% 12, 35% 2, 6% 44.8 ± 5.1 7398.5 ± 1525.1 C4d+C3d+: n=30 28, 93% 20, 67% 26, 87% 18, 60% 87.4 ± 5.4 12633.0 ± 1222.8 C4d conv: n=11 11, 100% 4, 36% 10, 91% 3, 27% 81.1 ± 8.9 8378.2 ± 1950.9 p .0003 .005 .022 Table 2 Any DSA DSA Cl I DSA Cl II DR DSA DQ DSA cPRA≥50 C4d+: n=34 19, 56% 9, 26% 12, 35% 3, 9% 11, 32% 16, 47% C4d conv: n=11 11, 100% 4, 36% 10, 91% 6, 55% 9, 82% 10, 91% p .008 .70 .002 .003 .004 .014 PPV .38 .30 .46 .67 .45 .39 NPV 1 .78 .96 .86 .92 .95