58-P: CORRELATION OF CIRCULATING COMPLEMENT-FIXING DONOR SPECIFIC ANTIBODIES IDENTIFIED BT THE C1q ASSAY AND PRESENCE OF C4d in ENDOMYOCARDIAL BIOPSY: A SINGLE-CENTER RETROSPECTIVE STUDY

Abstract

Aim Donor-specific antibodies (DSA) are associated with increased cardiac graft loss. Detection of antibody-mediated rejection (AMR) relies on graft dysfunction, C4d immunofluorescence (IF) and DSA. We applied a C1q solid-phase assay in parallel with the standard IgG SAB assay to examine the correlation of circulating complement-fixing donor-specific antibodies and presence of C4d in endomyocardial biopsy (EMB). Methods We retrospectively studied the relationship of C1q+ DSA, and C4d IF in 40 EMB from 38 cases of heart transplant recipients (The Journal of Heart and Lung Transplantation, Vol 32, No 4, April 2013). C4d evaluation was performed for cause, including (1) clinical evidence of graft dysfunction; (2) high PRA; and (3) ACR, ISHLT Grade 3R. We applied a C1q solid-phase assay in parallel with the standard IgG SAB assay to examine the DSA profiles in heart transplant patients post-transplant. The MFI cut off values of IgG DSA and C1q+ DSA are > 1,000 and >200 respectively. Results A better concordance is observed between C1q+ DSA with C4d IF+ as compared to IgG DSA with C4d IF+ (54% vs.24%, p = 0.09, paired samples T test). However, the correlation of C1q DSA with C4d IF is not statistically significant ( p = 0.12, Fisher Exact test). Importantly, C1q+ DSA is observed in 14/15 cases with C4d IF +; 17 cases had circulating C1q+ DSA without detectable C4d staining (Table), suggesting that that the presence of C1q+ DSA may precede the detection of C4d deposition in EMB and/or the development of AMR. [ Table 1 ] Conclusions In this cohort of 38 patients, no significant correlation is observed between circulating C1q DSA and C4d IF in EMB. Additional studies are needed to further evaluate the association of C1q DSA with EMB and IF C4d staining, and with long-term outcomes in heart transplant recipients.