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.