Not All Antibodies Are Created Equal: Factors That Influence Antibody Mediated Rejection

Figure 1

Factors influencing AMR. Schematic of the antibody components that influence AMR’s pathogenesis. Depicted are the antibody factors (blue) that influence AMR pathology (shown in red). Antibody factors influencing AMR include sensitization pretransplant and antibody attributes such as specificity, ability to bind complement, isotype/subclass, strength (MFI/titer), density, affinity, and glycosylation. AMR histology (red) includes graft dysfunction, endothelial cell (EC) swelling, microvascular inflammation, and macrophage infiltrate and can occur with or without complement deposition. The three outcomes after DSA include stable function, subclinical AMR and clinical dysfunction with AMR (either acute or chronic). Stable function in the presence of DSA is typically seen in those patients with IgG2/IgG4 antibodies that do not show signs of complement binding antibodies (C1q−, C4d−). Subclinical AMR is typically seen in those patients with IgG2/IgG4 antibodies that may show signs of complement binding antibodies (C1q−, C4d±). Clinical dysfunction with AMR can be grouped into acute or chronic AMR. Acute AMR is typically seen in those patients with IgG3/IgG1 antibodies that are complement binding antibodies (C1q+, C4d+). Chronic AMR is typically seen in those patients with IgG2/IgG4 antibodies that may or may not include complement binding antibodies (C1q±, C4d±).