Donor-specific antibodies and pathogenic autoantibodies (DSA/AutoAb)

Donor-specific antibodies (DSAs) and pathogenic autoantibodies are specialized immunoglobulins, primarily of the IgG class, that inappropriately target non-self donor tissues or the body's own antigens. DSAs are a primary driver of antibody-mediated rejection (AMR) in solid organ transplantation, where they bind to Human Leukocyte Antigens (HLA) on the graft, triggering complement activation and subsequent tissue damage [1]. Pathogenic autoantibodies underlie various autoimmune disorders by interfering with cellular signaling, inducing inflammation, or promoting the destruction of host tissues [2]. Modern therapeutic strategies focus on reducing the levels of these antibodies through physical removal via plasmapheresis, enzymatic degradation using agents like imlifidase, or by blocking the neonatal Fc receptor (FcRn) to accelerate their natural clearance [3]. Additionally, therapies may target the B cells and plasma cells responsible for the production of these antibodies to provide long-term disease control [4]. Monitoring the titers and specificity of these antibodies is essential for diagnosing rejection, managing autoimmune flares, and assessing the efficacy of desensitization protocols [5]. [1] Colvin, R. B., & Smith, R. N. (2005). Antibody-mediated organ-allograft rejection. Nature Reviews Immunology. [2] Ludwig, R. J., et al. (2017). Mechanisms of Autoantibody-Induced Pathology. Frontiers in Immunology. [3] Gable, K. L., & Guptill, J. T. (2019). Antagonism of the Neonatal Fc Receptor as a Therapeutic Strategy in Myasthenia Gravis. Frontiers in Neurology. [4] Jordan, S. C., et al. (2011). Intravenous immunoglobulin and rituximab for desensitization of highly HLA-sensitized patients. American Journal of Transplantation. [5] Valenzuela, N. M., & Reed, E. F. (2013). Antibodies in transplantation: the effects of HLA and non-HLA antibody binding and complement activation. Pediatric Nephrology.

Other names

Anti-HLA antibodiesSelf-reactive antibodiesPathogenic immunoglobulinsAlloantibodiesAutoantibodiesHumoral antibodies

Enzymatic cleavage of IgG hinge region to prevent effector functions; inhibition of the neonatal Fc receptor (FcRn) to accelerate IgG degradation; depletion of B cells or plasma cells to inhibit antibody production; physical removal via plasmapheresis or immunoadsorption.