title: The importance of non-HLA antibodies in transplantation.
abstract: The development of post-transplantation antibodies against non-HLA autoantigens is associated with rejection and decreased long-term graft survival. Although our knowledge of non-HLA antibodies is incomplete, compelling experimental and clinical findings demonstrate that antibodies directed against autoantigens such as angiotensin type 1 receptor, perlecan and collagen, contribute to the process of antibody-mediated acute and chronic rejection. The mechanisms that underlie the production of autoantibodies in the setting of organ transplantation is an important area of ongoing investigation. Ischaemia-reperfusion injury, surgical trauma and/or alloimmune responses can result in the release of organ-derived autoantigens (such as soluble antigens, extracellular vesicles or apoptotic bodies) that are presented to B cells in the context of the transplant recipient's antigen presenting cells and stimulate autoantibody production. Type 17 T helper cells orchestrate autoantibody production by supporting the proliferation and maturation of autoreactive B cells within ectopic tertiary lymphoid tissue. Conversely, autoantibody-mediated graft damage can trigger alloimmunity and the development of donor-specific HLA antibodies that can act in synergy to promote allograft rejection. Identification of the immunologic phenotypes of transplant recipients at risk of non-HLA antibody-mediated rejection, and the development of targeted therapies to treat such rejection, are sorely needed to improve both graft and patient survival.
authors.affiliation: UCLA Immunogenetics Center, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California Los Angeles, 1000 Veteran Avenue, Los Angeles, California 90095, USA.
authors.forename: Qiuheng
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: UCLA Immunogenetics Center, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California Los Angeles, 1000 Veteran Avenue, Los Angeles, California 90095, USA.
authors.forename: Elaine F
authors.initials: EF
authors.lastname: Reed
mesh_terms: D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D003094:Collagen / Q000276:immunology; D019812:Heparan Sulfate Proteoglycans / Q000276:immunology; D006801:Humans; D016030:Kidney Transplantation; D044140:Receptor, Angiotensin, Type 1 / Q000276:immunology; D014181:Transplantation Immunology
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D019812:Heparan Sulfate Proteoglycans; D044140:Receptor, Angiotensin, Type 1; C071927:perlecan; D003094:Collagen