Effect of Immunosuppressive Drugs on Humoral Allosensitization after Kidney Transplant

Abstract

The negative effect of donor-specific antibodies on the success of solid transplant is now clearly established. However, the lack of effective treatment to prevent the development of antibody-mediated lesions deepens the need for clinicians to focus on primary prevention of de novo humoral allosensitization. Among the factors associated with the risk of developing de novo donor-specific antibodies, therapeutic immunosuppression is the most obvious parameter in which improvement is possible. Beyond compliance and the overall depth of immunosuppression, it is likely that the nature of the drugs is also crucial. Here, we provide an overview of the molecular effect of the various immunosuppressive drugs on B cell biology. Clinical data related to the effect of these drugs on de novo humoral allosensitization are also examined, providing a platform from which clinicians can optimize immunosuppression for prevention of de novo donor-specific antibody generation at the individual level.

Keywords: immunology; immunosuppression; renal transplantation.

Figure 1.

Key molecular steps of B cell activation and sites of action of immunosuppressive drugs. B cell activation is a two-step process. (Top panel) Binding of the cognate antigen to the surface Ig of B cells serves as the first signal of activation. BCR signaling drives the internalization of bound antigens (donor’s HLA molecules) to endosomal compartments, where they are processed. Selected peptides are then loaded onto recipient MHC class 2 molecules and presented on the B cell surface. (Bottom panel) B cells interact with cognate Tfh cells that provide the second costimulation signal for the completion of B cell activation. Therapies with proven efficiency are shown as red lines. Putative mechanisms of action are dashed red lines with question marks. TCR, T cell receptor.