title: The Lymphatic Phenotype of Lung Allografts in Patients With Bronchiolitis Obliterans Syndrome and Restrictive Allograft Syndrome.
abstract: Chronic lung allograft dysfunction (CLAD), presenting as bronchiolitis obliterans syndrome (BOS) or restrictive allograft syndrome (RAS) is the major limiting factor of long-term survival in lung transplantation. Its pathogenesis is still obscure. In BOS, persistent alloimmune injury and chronic airway inflammation are suggested. One of the main tasks of the lymphatic vessel (LV) system is the promotion of immune cell trafficking. The formation of new LVs has been shown to trigger chronic allograft rejection in kidney transplants. We therefore sought to address the role of lymphangiogenesis in CLAD.
  
  
  
  Formalin-fixed paraffin-embedded tissue samples of 22 patients receiving a lung retransplantation due to BOS or RAS were collected. Lymphatic vessel density (LVD) was determined by immunohistochemical staining for podoplanin. Lung tissue obtained from 13 non-CLAD patients served as control. The impact of LVD on graft survival was assessed.
  
  
  
  Lymphatic vessel density in CLAD patients did not differ from those in control subjects (median number of LVs per bronchiole: 4.75 (BOS), 6.47 (RAS), 4.25 (control), P = 0.97). Moreover, the number of LVs was not associated with regions of cellular infiltrates (median number of LVs per bronchiole: with infiltrates, 5.00 (BOS), 9.00 (RAS), 4.00 (control), P = 0.62; without infiltrates, 4.5 (BOS), 0.00 (RAS), 4.56 (control), P = 0.74). Lymphatic vessel density did not impact the time to development of BOS or RAS in lung transplantation (low vs high LVD: 38.5 vs 86.0 months, P = 0.15 [BOS]; 60.5 vs 69.5 months, P = 0.80 [RAS]).
  
  
  
  Unlike chronic organ failure in kidney transplantation, lymphangiogenesis is not altered in CLAD patients. Our findings highlight unique immunological processes leading to BOS and RAS.
authors.affiliation: 1 Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria. 2 Christian Doppler Laboratory for Cardiac and Thoracic Diagnosis and Regeneration, Medical University of Vienna, Vienna, Austria. 3 Department of Thoracic Surgery, Semmelweis University, Budapest, Hungary. 4 Clinical Institute of Pathology, Medical University of Vienna, Vienna, Austria.
authors.forename: Denise
authors.initials: D
authors.lastname: Traxler
authors.forename: Thomas
authors.initials: T
authors.lastname: Schweiger
authors.forename: Stefan
authors.initials: S
authors.lastname: Schwarz
authors.forename: Magdalena Maria
authors.initials: MM
authors.lastname: Schuster
authors.forename: Peter
authors.initials: P
authors.lastname: Jaksch
authors.forename: Gyoergy
authors.initials: G
authors.lastname: Lang
authors.forename: Peter
authors.initials: P
authors.lastname: Birner
authors.forename: Walter
authors.initials: W
authors.lastname: Klepetko
authors.forename: Hendrik Jan
authors.initials: HJ
authors.lastname: Ankersmit
authors.forename: Konrad
authors.initials: K
authors.lastname: Hoetzenecker
mesh_terms: D000328:Adult; D064591:Allografts; D015415:Biomarkers / Q000032:analysis; D055745:Bronchioles / Q000737:chemistry / Q000276:immunology / Q000473:pathology*; D001989:Bronchiolitis Obliterans / Q000209:etiology / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D016040:Lung Transplantation / Q000009:adverse effects*; D042583:Lymphangiogenesis; D042601:Lymphatic Vessels / Q000737:chemistry / Q000276:immunology / Q000473:pathology*; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis; D008875:Middle Aged; D013577:Syndrome; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult; D000098853:Podoplanin
chemical_list: D015415:Biomarkers; D008562:Membrane Glycoproteins; C117468:PDPN protein, human; D000098853:Podoplanin