title: Humoral immunity and complement effector mechanisms after lung transplantation.
abstract: Lung transplantation (LTx) is the final treatment option for patients with endstage lung diseases including chronic obstructive pulmonary disease, cystic fibrosis, and interstitial lung disease. Survival after LTx is severely hampered by the development of the bronchiolitis obliterans syndrome (BOS) which is hallmarked by excessive fibrosis and scar tissue formation leading to small airway obliteration and eventually organ failure. The pathophysiology of BOS is incompletely understood. During the past years both anti-HLA and non-HLA antibodies have been identified that correlate with transplantation outcome. Also, the involvement of autoimmunity on BOS progression has been demonstrated, including autoantigens Type V collagen and K-alpha tubulin. Both allo- and autoantibodies binding to its respective antigen trigger the binding of C1q and sequential complement activation which can lead to either cell damage or activation, both processes which fit into the current model of BOS pathogenesis. In this review we will discuss both HLA, non-HLA and autoantibodies associated with disease progression, but also elaborate on the subsequent complement effector mechanisms, complement regulation, and the potential influence of regulatory mechanisms on graft survival.
authors.affiliation: Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands. Electronic address: k.budding@umcutrecht.nl.
authors.forename: K
authors.initials: K
authors.lastname: Budding
authors.affiliation: Department of Respiratory Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: E A
authors.initials: EA
authors.lastname: van de Graaf
authors.affiliation: Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: H G
authors.initials: HG
authors.lastname: Otten
mesh_terms: D001323:Autoantibodies / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology*; D001989:Bronchiolitis Obliterans / Q000276:immunology*; D024062:Collagen Type V / Q000276:immunology; D003167:Complement Activation / Q000276:immunology; D015922:Complement C1q / Q000276:immunology*; D006084:Graft Rejection / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D056724:Immunity, Humoral / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000473:pathology / Q000601:surgery; D016040:Lung Transplantation / Q000009:adverse effects*; D014404:Tubulin / Q000276:immunology
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D024062:Collagen Type V; D006680:HLA Antigens; D014404:Tubulin; D015922:Complement C1q
keywords: Alloimmunity; Autoimmunity; Complement regulation; Lung transplantation