Concomitant C4d and C3d detection in heart biopsies correlates with circulating DSA and graft dysfunction. Detection of C4d only in surveillance biopsies is not associated with graft dysfunction in majority of cases. However, conversion from C4d+ to C4d+ and C3d+ is observed in 20% of cases (C4d converters). We compare DSA patterns among patients with clinical (C4d+C3d+ & C4d converters) and subclinical (C4d+) AMR.

Of 1589 transplants, 610 were screened for AMR in the last 6 years. Three groups were investigated including asymptomatic patients with C4d+ biopsies till last follow up (n=34), symptomatic patients with C4d+C3d+ biopsy (n=30) and patients who started as C4d+ then converted to C4d+C3d+ (n=11). We investigate DSA characteristics of the sera within one week of the 1st biopsy. DSA characteristics included Class I vs. II, breadth (cPRA), and strength (MFI of the highest reacting DSA). We also compare pre-transplant DSA, cPRA and crossmatch results.

No significant differences were noted among groups in pre-transplant mean cPRA, incidence of DSA, or positive crossmatch. In contrast, at time of initial biopsy, significant differences in incidence of DSA, mean cPRA, and mean MFI were noted (table 1).

C4d+ converters had significantly higher incidence of DSA, driven by HLA-DQ & higher mean cPRA compared to patients who remained C4d+.

Having DSA particularly HLA-DQ or cPRA ≥50% at time of biopsy was associated with C4d+ conversion with high negative predictive value (NPV) but low positive predictive value (PPV).

HLA antibody characteristics correlate with C4d+/C3d+ patterns and may be relevant in determining which subclinical C4d+ patients may not progress to clinical AMR.

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