title: Non-HLA antibodies in solid organ transplantation: recent concepts and clinical relevance.
abstract: OBJECTIVE
  Humoral responses beyond major histocompatibility antigens continue to receive the attention of the transplantation community. We report on clinical studies testing clinical relevance of non-human leukocyte antigen (HLA) antigens in solid organ transplantation and provide an update on novel experimental findings. A conceptual framework on the role of graft microenvironment during initiation of non-HLA-related humoral immunity is addressed as well.
  
  
  RESULTS
  Clinical relevance of antibodies targeting angiotensin type 1 receptor (AT1R-Abs) is broadly confirmed in renal and cardiac transplantation, where in addition antibodies against endothelin type A receptor (ETAR-Abs) were found. Obliterative lesions in lung allografts occur more commonly in the presence of antibodies directed against K-α 1 tubulin and collagen-V. Anti-perlecan antibodies are newly identified as accelerators of obliterative vascular lesions. Changes in the intragraft microenvironment, ischemia and alloimmunity seem to represent important permissive factors for non-HLA antibody responses.
  
  
  CONCLUSIONS
  Confirmed clinical relevance of non-HLA humoral responses in solid organ transplantation emphasizes the need for revision of classical diagnostic approaches based solely on detection of HLA-donor-specific antibodies (DSA). A better understanding of intersections of HLA- and non-HLA-related mechanisms and identification of common effector mechanisms would represent an important step towards targeted therapies.
authors.affiliation: Clinic for Nephrology and Intensive Care Medicine Campus Virchow-Klinikum and Center for Cardiovascular Research, Medical Faculty of the Charité, Berlin, Germany. duska.dragun@charite.de
authors.forename: Duska
authors.initials: D
authors.lastname: Dragun
authors.forename: Rusan
authors.initials: R
authors.lastname: Catar
authors.forename: Aurélie
authors.initials: A
authors.lastname: Philippe
mesh_terms: D001323:Autoantibodies / Q000097:blood*; D024062:Collagen Type V / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology; D019812:Heparan Sulfate Proteoglycans / Q000276:immunology*; D006801:Humans; D056724:Immunity, Humoral / Q000502:physiology; D016377:Organ Transplantation; D044140:Receptor, Angiotensin, Type 1 / Q000276:immunology*; D044022:Receptor, Endothelin A / Q000276:immunology*; D014404:Tubulin / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D024062:Collagen Type V; D006680:HLA Antigens; D019812:Heparan Sulfate Proteoglycans; D044140:Receptor, Angiotensin, Type 1; D044022:Receptor, Endothelin A; D014404:Tubulin; C071927:perlecan