title: Molecular targets on B-cells to prevent and treat antibody-mediated rejection in organ transplantation. Present and Future.
abstract: BACKGROUND
  Waiting lists for transplant are increasing day after day since transplantation is still the best option for the treatment of end-stage organ failure. Likewise, our increasing knowledge about how immune system mounts the response against allograft is at the point that up to 95% of acute T-cell-mediated rejections are effectively controlled by current immunosuppressive therapy. Nevertheless, this is not the case for acute and chronic antibody-mediated rejections (ABMR), where treatments to reduce the level of donor specific antibodies (DSAs) remain suboptimal, causing the majority of acute and chronic graft losses.
  
  
  METHODS
  T-cell immunosuppressant agents are usually ineffective to treat humoral rejection and current strategies to prevent ABMR include plasmapheresis; high doses of intravenous immunoglobulin; anti-CD20 monoclonal antibodies to treat B-cells; and in some cases Bortezomib, which mainly affects plasmoblast and plasma cells, or antibodies against components of complement cascade.
  
  
  CONCLUSIONS
  We reassess the B-cell ontogeny in order to propose new molecular targets that interrupt the antibody production pathways and their eventual pathological injury. We also take a look at the pharmaceutical industry to find agents that are currently being assayed for B-cell pathologies and that could be used in the future to prevent and treat ABMR.
authors.affiliation: a Immunology Service , Clinical University Hospital Virgen de la Arrixaca-IMIB , Murcia , Spain.
authors.forename: Jose A
authors.initials: JA
authors.lastname: Galián
authors.affiliation: a Immunology Service , Clinical University Hospital Virgen de la Arrixaca-IMIB , Murcia , Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Mrowiec
authors.affiliation: a Immunology Service , Clinical University Hospital Virgen de la Arrixaca-IMIB , Murcia , Spain.|b Head of Regional Histocompatibility and Transplant Immunology Laboratory (LRHI) , Clinical University Hospital Virgen de la Arrixaca-IMIB , Murcia , Spain.|c Net of Biomedical Research in Digestive and Liver Diseases (CIBERehd) , Barcelona , Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Muro
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D015195:Drug Design; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D058990:Molecular Targeted Therapy; D016377:Organ Transplantation / Q000379:methods*; D010956:Plasmapheresis / Q000379:methods; D013601:T-Lymphocytes / Q000276:immunology; D014184:Transplantation, Homologous
chemical_list: D000906:Antibodies; D007166:Immunosuppressive Agents
keywords: Antibody-mediated rejection; B-cell; kidney allograft; molecular target