Pilot evaluation of c1q screen in evaluation of patients for renal transplatation

Abstract

Anti-HLA analysis by luminex single antigen bead is well-established in patient evaluation pre-transplantation, despite concerns about oversensitivity, and lack of concensus concerning the clinically-relevant cut-off. A modified technique detecting only complement-fixing antibodies is commercially available. This assay is not CE-marked and labelled for research use only. Users are advised to “use a known positive and negative reference serum to determine assay cut-off”. The commercial assay appears to differ in configuration to that published in some papers. Aim: Pilot evaluation to determine if this novel assay differentiated donor specific antibodies (DSA) in patients who developed who developed antibody mediated rejection (AMR) post renal transplant from those who did not. Methods: 4 patients who developed AMR in the first 2 months post-transplant were compared with 13 patients, chosen because of positivity in IgG SAB assays who did not develop significant rejection post transplant. Standard IgG SAB assays were also performed. Results: 3/4 patients had donor-specific SAB positivity detectable on the day of transplant. All were negative for DSA in the C1q assay (positivity defined either by absolute or relative MFI). All of the patients with an uneventful post transplant course had IgG detectable in SAB assays (4 detectable in one assay only, and 9 positive in both SAB assays). 4 patients in the no-AMR group had donor specific C1q detected. Of the 4 patients with donor-specific C1q antibodies 2 have had prolonged graft function (9yrs & 12 yrs), while 2 grafts failed at 30 months and 4 years. Conclusion: In this pilot evaluation, the commercially-available C1q assay does not detect DSA in patients who subsequently develop AMR, even when these are detectable by IgG SAB. The presence of donor-specific C1q antibodies may be compatible with long-term graft survival.