Background: The ability of donor specific HLA antibodies (DSA) to fix complement is regarded to be a primary mechanism for antibody-mediated rejection of organ allografts. Recently, a Luminex-based solid phase C1q binding assay was developed to distinguish clinically relevant, complement fixing HLA antibodies from those that do not fix complement. Some previous studies indicated that C1q-binding DSAs correlate with rejection and are thus clinically significant, whereas non-C1q-binding DSA were not associated with increased risk of rejection. The objective of this study was to assess the validity of the C1q-binding assay to identify clinically-significant DSA. Methods: DSA-positive sera from 34 kidney recipients (19 with biopsy-proven AMR+ and 15 who were AMR-) were assayed in C1q binding assays (C1q Screen; One Lambda, Inc.). The correlation between C1q binding activity and AMR as well as DSA MFI value was assessed. Concentration of low MFI sera prior to testing in the C1q binding assay was accomplished using Centricon Ultracell-100 concentrators (Millipore). Results: A slight majority (10/19; 53%) of sera from AMR+ patients were C1q+, whereas only 2/15 (13%) of sera from AMR- patients were C1q+.
|AMR+||AMR-||Number of Patients|
|Number of Patients||19||15||34|
This observation is consistent with previous studies indicating that C1q binding activity identifies clinically significant DSA. However, comparison of mean MFI values of DSAs showed that C1q+ sera from either AMR+ or AMR- patients had much higher MFI values than C1q- sera from AMR+ or AMR- patients.
|C1q+||18,233 +/- 4,268*||11,784 +/- 11,224|
|C1q-||5,864 +/- 2,686||5,381 +/- 2,352|
Further, AMR+C1q+ sera converted to C1q- when diluted to a comparable MFI level as the C1q- DSA. Likewise C1q- sera from both AMR+ and AMR- patients converted to C1q+ when DSA were concentrated to MFI levels comparable to those observed for AMR+/C1q+ sera. Conclusions: The association between C1q binding activity by DSA and AMR in our patients appears largely to reflect quantitative differences in antibody levels, and we found no evidence that the C1q binding assay distinguishes clinically significant antibodies based on C1q functional activity.
To cite this abstract in AMA style:Ellis T, Yell M, Muth B, Brown P, Djamali A. Positive Solid Phase C1q Assays in Patients with Antibody-Mediated Rejection Correlate with the Presence of HLA Antibodies with High MFI Values [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/positive-solid-phase-c1q-assays-in-patients-with-antibody-mediated-rejection-correlate-with-the-presence-of-hla-antibodies-with-high-mfi-values/. Accessed October 27, 2020.
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