title: Bronchiolitis obliterans syndrome due to donor-specific HLA-antibodies.
abstract: Chronic lung allograft dysfunction (CLAD) is a limiting factor for long-term survival in lung transplant recipients. Donor-specific human leukocyte antigen (HLA)-antibodies (DSA) have been suggested as potential risk factors for CLAD. However, their impact on clinical outcome following lung transplantation remains controversial. We performed a single-center study of 120 lung transplant recipients transplanted between 2006 and 2011. Patient sera were investigated before and after transplantation. The sera were screened by means of Luminex(®) technology (Luminex Inc., Austin, TX, USA) for IgG-HLA-class I and class II antibodies (ab). Using single antigen beads, DSA were identified and correlated retrospectively with clinical parameters. After transplantation 39 out of 120 patients (32.5%) were positive for HLA-ab. The incidence of de novo DSA formation was 27 of 120 patients (22.5%). Eleven of 27 (41%) of de novo DSA-positive patients developed BOS compared to 13 of 93 (14%) DSA-negative patients (p = 0.002). Furthermore, the generation of de novo DSA was independently associated with the development of BOS in multivariable analysis [hazard ration (HR) 2.5, 95% confidence interval (CI) 1.0-6.08; p = 0.046). Our results indicate that de novo DSA are associated with the development of BOS after lung transplantation. Monitoring of HLA-ab after transplantation is useful for identifying high-risk patients and offers an opportunity for early therapeutic intervention.
authors.affiliation: Laboratory for Immunogenetics, University Hospital Grosshadern, Ludwig-Maximilians-University, Munich, Germany.|Department of General, Visceral, Transplantation, Vascular and Thoracic Surgery, University Hospital Grosshadern, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Kauke
authors.affiliation: Department of Internal Medicine V, University Hospital Grosshadern, Ludwig-Maximilians-University, and Asklepios Fachkliniken München-Gauting, Comprehensive Pneumology Center Munich (CPC-M), Member of the German Center for Lung Research (DZL), Munich, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Kneidinger
authors.affiliation: Department of Internal Medicine V, University Hospital Grosshadern, Ludwig-Maximilians-University, and Asklepios Fachkliniken München-Gauting, Comprehensive Pneumology Center Munich (CPC-M), Member of the German Center for Lung Research (DZL), Munich, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Martin
authors.affiliation: Laboratory for Immunogenetics, University Hospital Grosshadern, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Dick
authors.affiliation: Department of General, Visceral, Transplantation, Vascular and Thoracic Surgery, University Hospital Grosshadern, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Schneider
authors.affiliation: Department of Cardiac Surgery, University Hospital Grosshadern, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Schramm
authors.affiliation: Department of General, Visceral, Transplantation, Vascular and Thoracic Surgery, University Hospital Grosshadern, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Meimarakis
authors.affiliation: Department of General, Visceral, Transplantation, Vascular and Thoracic Surgery, University Hospital Grosshadern, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Preissler
authors.affiliation: Comprehensive Pneumology Center Munich (CPC-M), Institute of Lung Biology and Disease, Helmholtz Zentrum München, Member of the German Center for Lung Research (DZL), Munich, Germany.
authors.forename: O
authors.initials: O
authors.lastname: Eickelberg
authors.affiliation: Department of Anaesthesiology, University Hospital Grosshadern, Ludwig-Maximilians-University, Munich Lung Transplant Group (MLTP), Munich, Germany.
authors.forename: V
authors.initials: V
authors.lastname: von Dossow
authors.affiliation: Department of Internal Medicine V, University Hospital Grosshadern, Ludwig-Maximilians-University, and Asklepios Fachkliniken München-Gauting, Comprehensive Pneumology Center Munich (CPC-M), Member of the German Center for Lung Research (DZL), Munich, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Behr
authors.affiliation: Department of General, Visceral, Transplantation, Vascular and Thoracic Surgery, University Hospital Grosshadern, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Hatz
authors.affiliation: Department of Internal Medicine V, University Hospital Grosshadern, Ludwig-Maximilians-University, and Asklepios Fachkliniken München-Gauting, Comprehensive Pneumology Center Munich (CPC-M), Member of the German Center for Lung Research (DZL), Munich, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Neurohr
authors.affiliation: Department of General, Visceral, Transplantation, Vascular and Thoracic Surgery, University Hospital Grosshadern, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Winter
mesh_terms: D000328:Adult; D000906:Antibodies / Q000276:immunology*; D001989:Bronchiolitis Obliterans / Q000276:immunology*; D005260:Female; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D016040:Lung Transplantation; D008297:Male; D008875:Middle Aged; D014019:Tissue Donors
chemical_list: D000906:Antibodies; D006680:HLA Antigens
keywords: bronchiolitis obliterans syndrome; chronic lung allograft dysfunction; human leukocyte antigen-antibodies; humoral rejection; lung transplantation