C1Q: A NOVEL ASSAY FOR PREDICTING CLINICALLY RELEVANT ANTIBODY

摘要

The IgG SAB assay does not distinguish binding antibody from complement (C) fixing antibody. The clinical relevance of binding (but not C fixing) antibody is unknown and may even be benign or beneficial (e.g., accommodation). In contrast to the insensitive and nonspecific C4d Luminex~R (LMX) assay (1), our laboratory has developed a new assay (C1q SAB) using the highly sensitive and specific SABs to detect the presence of C fixing HLA antibody (HLA-Ab) not detectable by traditional cytotoxicity assays. The patient's own C or exogenous human C1q (as opposed to rabbit C used in the CDC assay) must bind to these antibodies and should portend C4d deposition (clinically relevant) due to HLA-Ab. We therefore sought to demonstrate the clinical utility of the C1q SAB assay in donor selection and risk assessment for antibody mediated rejection post-heart transplantation. Additionally, while IVIG has a beneficial effect in reducing HLA-Ab in highly sensitized patients, it non-specifically binds to the surface of cells and any solid phase used in HLA-Ab detection assays. The C1q assay successfully eliminates the false positive and high BG signals due to IVIG. Based on the same principle, LMX-C1q-IVIG was developed to predict in vivo IVIG efficacy for lowering HLA-Ab.