Horizons in TransplantationExperimental transplantationPrediction of Complement-Binding Capacity of HLA Antibodies Based on Mean Fluorescence Intensity

•Complement activation is initiated by C1q binding, which depends on the density of bound IgG HLA antibodies and IgG subclass.•C1q-Luminex assay measuring C1q binding with HLA antibodies has recently been introduced.•The correlation between the strength of HLA antibodies and the ability to bind C1q is not universally accepted.•This study found that the mean fluorescence intensity of HLA antibodies using the IgG-Luminex partially predicted the C1q-binding before transplantation.

BackgroundHuman leukocyte antigen (HLA) antibodies estimated by Luminex single-antigen beads, especially those that fix complement, are associated with antibody-mediated rejection and graft failure. However, the relationship between HLA antibody strength and complement-binding ability is controversial.MethodsSerum samples of 31 sensitized renal patients waiting for renal transplantation were retrospectively analyzed by IgG-Luminex to identify HLA antibodies and in parallel by C1q-Luminex to determine the complement binding of HLA antibodies.ResultsThe percentage of HLA class I antibodies binding with C1q was lower than that of HLA class II antibodies (43.2% vs. 51.3%, P = .006). The mean fluorescence intensities (MFI) of IgG-Luminex correlated with the MFI of C1q-Luminex for the same antibodies (Spearman correlation; class I, r = 0.665, P < .01; class II, r = 0.761, P < .01). Receiver operating characteristic (ROC) curve analysis showed that the MFIs of HLA antibodies by IgG-Luminex predicted their C1q-binding abilities (area under the curve [AUC] class I = 0.917; AUC class II = 0.927). Using MFI cutoff values of 8238 and 6754 in IgG-Luminex for HLA class I and class II antibodies, respectively, the sensitivity and specificity for C1q binding were 82.4% and 87.4% for class I antibodies and 90.9% and 82% for class II antibodies.ConclusionsThe MFI of HLA antibodies by IgG-Luminex predicts the complement-binding capability to a certain extent before transplantation.