Anti-HLA Donor-Specific IgG Subclasses and C1q-binding Evolution in Posttransplant Monitoring

Abstract

Background: The identification of low-level antibodies by single-antigen bead methodology has brought advancements to risk evaluation of kidney transplant recipients. However, the use of mean fluorescence intensity (MFI) to quantify antibodies and to guide therapy is not enough. Notably, immunoglobulin G (IgG) subclass switching is hypothesized to follow a programmed sequence after an emergency signal from the germinal center. In transplantation this process is not clear yet. In the present study, we sequentially evaluate anti-HLA donor specific antibody (DSA) subclasses, their profile changes, and C1q-binding ability and the influence of those characteristics on antibody mediated rejection (AMR) occurrence and allograft function.

Methods: A total of 30 DSA-positive patients were tested for IgG subclass content and C1q-binding in sequential serum samples.

Results: Twenty-one patients were DSA-positive before transplant; patients sensitized only by transfusion or pregnancies had IgG1 and/or IgG3, and patients sensitized by both transfusion and pregnancies or previous transplant showed a broader range of IgG subclasses. C1q binding was detected in high MFI made up of IgG1 or multiple IgG subclasses. Only 4 patients were positive for C1q posttransplantation and 3 of these showed an increase in MFI, changes in subclasses patterns, AMR, and allograft dysfunction.

Conclusions: Posttransplant evaluation of DSA subclasses and the ability to bind C1q may be informative for both AMR occurrence and allograft dysfunction. Monitoring these events may help to better define risk and interventional time points.

FIGURE 1

Sera samples collected during prospective posttransplant monitoring.

FIGURE 2

Study population according to anti-HLA DSA and C1q-binding status. C1q+-C1q-binding positive; C1q−-C1q-binding negative.

FIGURE 3

Evolution of allograft function. A, Comparison of means of allograft function measured by eGFR by MDRD according to the presence of anti-HLA DSAs with or without C1q-binding by each period of time evaluated. B, Evolution of allograft function over time evaluated by repeated-measures ANOVA according to C1q-binding status.