title: Immunological diversity in phenotypes of chronic lung allograft dysfunction: a comprehensive immunohistochemical analysis.
abstract: Chronic rejection after organ transplantation is defined as a humoral- and cell-mediated immune response directed against the allograft. In lung transplantation, chronic rejection is nowadays clinically defined as a cause of chronic lung allograft dysfunction (CLAD), consisting of different clinical phenotypes including restrictive allograft syndrome (RAS) and bronchiolitis obliterans syndrome (BOS). However, the differential role of humoral and cellular immunity is not investigated up to now. Explant lungs of patients with end-stage BOS (n = 19) and RAS (n = 18) were assessed for the presence of lymphoid (B and T cells) and myeloid cells (dendritic cells, eosinophils, mast cells, neutrophils, and macrophages) and compared to nontransplant control lung biopsies (n = 21). All myeloid cells, with exception of dendritic cells, were increased in RAS versus control (neutrophils, eosinophils, and mast cells: all P < 0.05, macrophages: P < 0.001). Regarding lymphoid cells, B cells and cytotoxic T cells were increased remarkably in RAS versus control (P < 0.001) and in BOS versus control (P < 0.01). Interestingly, lymphoid follicles were restricted to RAS (P < 0.001 versus control and P < 0.05 versus BOS). Our data suggest an immunological diversity between BOS and RAS, with a more pronounced involvement of the B-cell response in RAS characterized by a structural organization of lymphoid follicles. This may impact future therapeutic approaches.
authors.affiliation: Lung Transplant Unit, Division of Respiratory Disease, Department of Clinical and Experimental Medicine, KULeuven, Leuven, Belgium.
authors.forename: Elly
authors.initials: E
authors.lastname: Vandermeulen
authors.affiliation: Lung Transplant Unit, Division of Respiratory Disease, Department of Clinical and Experimental Medicine, KULeuven, Leuven, Belgium.
authors.forename: Elise
authors.initials: E
authors.lastname: Lammertyn
authors.affiliation: Lung Transplant Unit, Division of Respiratory Disease, Department of Clinical and Experimental Medicine, KULeuven, Leuven, Belgium.
authors.forename: Stijn E
authors.initials: SE
authors.lastname: Verleden
authors.affiliation: Lung Transplant Unit, Division of Respiratory Disease, Department of Clinical and Experimental Medicine, KULeuven, Leuven, Belgium.
authors.forename: David
authors.initials: D
authors.lastname: Ruttens
authors.affiliation: Lung Transplant Unit, Division of Respiratory Disease, Department of Clinical and Experimental Medicine, KULeuven, Leuven, Belgium.
authors.forename: Hannelore
authors.initials: H
authors.lastname: Bellon
authors.affiliation: Lung Transplant Unit, Division of Respiratory Disease, Department of Clinical and Experimental Medicine, KULeuven, Leuven, Belgium.
authors.forename: Mario
authors.initials: M
authors.lastname: Ricciardi
authors.affiliation: Lung Transplant Unit, Division of Respiratory Disease, Department of Clinical and Experimental Medicine, KULeuven, Leuven, Belgium.
authors.forename: Jana
authors.initials: J
authors.lastname: Somers
authors.affiliation: Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.
authors.forename: Ken R
authors.initials: KR
authors.lastname: Bracke
authors.affiliation: Translational Cell & Tissue Research Unit, Department of Imaging & Pathology, KULeuven, Leuven, Belgium.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Van Den Eynde
authors.affiliation: Translational Cell & Tissue Research Unit, Department of Imaging & Pathology, KULeuven, Leuven, Belgium.
authors.forename: Thomas
authors.initials: T
authors.lastname: Tousseyn
authors.affiliation: Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.
authors.forename: Guy G
authors.initials: GG
authors.lastname: Brusselle
authors.affiliation: Translational Cell & Tissue Research Unit, Department of Imaging & Pathology, KULeuven, Leuven, Belgium.
authors.forename: Erik K
authors.initials: EK
authors.lastname: Verbeken
authors.affiliation: Lung Transplant Unit, Division of Respiratory Disease, Department of Clinical and Experimental Medicine, KULeuven, Leuven, Belgium.
authors.forename: Johny
authors.initials: J
authors.lastname: Verschakelen
authors.affiliation: HILA laboratory, Rode Kruis Vlaanderen, Mechelen, Belgium.
authors.forename: Marie-Paule
authors.initials: MP
authors.lastname: Emonds
authors.affiliation: Lung Transplant Unit, Division of Respiratory Disease, Department of Clinical and Experimental Medicine, KULeuven, Leuven, Belgium.
authors.forename: Dirk E
authors.initials: DE
authors.lastname: Van Raemdonck
authors.affiliation: Lung Transplant Unit, Division of Respiratory Disease, Department of Clinical and Experimental Medicine, KULeuven, Leuven, Belgium.
authors.forename: Geert M
authors.initials: GM
authors.lastname: Verleden
authors.affiliation: Lung Transplant Unit, Division of Respiratory Disease, Department of Clinical and Experimental Medicine, KULeuven, Leuven, Belgium.
authors.forename: Robin
authors.initials: R
authors.lastname: Vos
authors.affiliation: Lung Transplant Unit, Division of Respiratory Disease, Department of Clinical and Experimental Medicine, KULeuven, Leuven, Belgium.
authors.forename: Bart M
authors.initials: BM
authors.lastname: Vanaudenaerde
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D006084:Graft Rejection / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D008168:Lung / Q000473:pathology; D008171:Lung Diseases / Q000276:immunology* / Q000473:pathology; D016040:Lung Transplantation / Q000009:adverse effects*; D008214:Lymphocytes; D008297:Male; D008875:Middle Aged; D022423:Myeloid Cells; D012189:Retrospective Studies; D055815:Young Adult
keywords: antibody-mediated rejection; broncho-alveolar lavage fluid; chronic lung allograft dysfunction; immunohistochemistry