Duska Dragun1, Rusan Catar, Aurélie Philippe. 1. 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
Abstract
PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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. SUMMARY: 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.
PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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. SUMMARY: 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: Shaikh M Atif; Michelle K Nelsen; Sophie L Gibbings; A Nicole Desch; Ross M Kedl; Ronald G Gill; Philippa Marrack; Kenneth M Murphy; Todd J Grazia; Peter M Henson; Claudia V Jakubzick Journal: J Immunol Date: 2015-06-01 Impact factor: 5.422
Authors: Karla Lehle; Johannes Kroher; Philipp Kolat; Marietta von Süßkind-Schwendi; Christof Schmid; Assad Haneya; Leopold Rupprecht; Stephan Hirt Journal: Heart Vessels Date: 2015-03-28 Impact factor: 2.037