Application, technical issues, and interpretation of C1q for graft outcome.

PURPOSE OF REVIEW: Significant interest and controversy surround the use of C1q for determining risk of antibody-mediated rejection (AMR) and graft loss. Alternate models for predicting outcomes have been proposed. This review focuses on the correlation of currently utilized assays for outcome, together with the technical and theoretical limitations, to distill current thinking.

RECENT FINDINGS: Results demonstrate that C1q status is significantly correlated with AMR and graft loss. There is general consensus that C1q is more clinically relevant for graft outcome than neat IgG MFI. IgG titers, subclass, and other complement assays have now been studied to determine if they are more relevant. Only IgG3 and possibly C3d fixation have shown added value to C1q for outcome correlation. Direct parallel titer comparisons of C1q and IgG are lacking and the correlation is unknown.

SUMMARY: Overall, results confirm the correlation with C1q+ donor-specific antibody (DSA) for AMR and graft loss. The association is stronger posttransplant. C1q+ de novo antibody appears to be especially detrimental portending graft loss in about 1-2.5 years post detection. Recommendations to biopsy and treat at time of de novo C1q+ antibody detection have been suggested by several groups.