Can C1q in Endomyocardial Biopsies (EMB) Predict AMR and Adverse Outcome?

Abstract

<h3>Purpose</h3> Single antigen bead flow assays with C1q spiking (C1q SAB) are reported to better predict early antibody-mediated rejection (AMR) in cardiac transplant patients. We wondered whether finding C1q co-localized with IgG in the capillaries of cardiac transplant biopsies would have similar predictive value. <h3>Methods and Materials</h3> Initially in our program, C1q staining was performed and recorded along with C3d staining as a measure of complement activation prior to use of C4d. The UTAH Cardiac Pathology Database also contains retrospectively assigned pAMR scores, based on specific histologic and immunopathologic parameters recorded separately (C1q did not figure into these scores). Outcome data (graft dysfunction, CAV, mortality, and cause of death) are also recorded, We correlated the presence of C1q with pAMR and outcome in a time varying Cox proportional hazard model. <h3>Results</h3> 788 patients with 10,236 EMBs were analyzed. Using the model of pAMR as predictor for adverse cardiovascular outcomes that we have reported previously, our prediction of adverse outcome was not enhanced in patients with C1q found on biopsy in addition to C3d or C4d. p=0.8598. Adding IgG as a co-variate strengthened the prediction, but not significantly, p=0.62. [figure 1] <h3>Conclusions</h3> While serum C1q SAB assays are useful in predicting AMR, detection of bound C1q in biopsy tissue did not improve our ability to predict adverse CV outcomes (in contrast to C4d). We conclude that there is no benefit to adding C1q detection on biopsy in the current ISHLT schema for AMR. This is likely due to the transient nature of C1q binding (unlike C3d and C4d), though the precise relationship between serum and tissue C1q in heart transplantation requires further study.