title: Humoral immunity in phenotypes of chronic lung allograft dysfunction: A broncho-alveolar lavage fluid analysis.
abstract: Recently, antibody mediated rejection (AMR) has been associated with a higher incidence of chronic lung allograft dysfunction (CLAD) and mortality after lung transplantation (LTx). We investigated markers related to AMR and matrix remodeling in CLAD, with special attention for its two phenotypes being bronchiolitis obliterans syndrome (BOS) and restrictive CLAD (rCLAD).
  
  
  
  Immunoglobulins (IgA, IgE, IgG1-IgG4, total IgG and IgM) and complement (C4d and C1q) were quantified in lung lavage samples at the moment of BOS (n=15) or RAS (n=16) diagnosis; and were compared to stable transplant patients who served as control (n=14). Also, airway remodeling and metalloproteinases (MMPs) were investigated via zymography and gelatin degradation. The presence of DSA was additionally assessed in blood.
  
  
  
  Total IgG, IgG1-IgG4 and IgM were increased in rCLAD versus control (p<0.001) and BOS patients (p<0.01). IgA and IgE were increased in rCLAD compared to control (respectively p<0.05 and p<0.01), but not to BOS. Total IgG and IgE were increased in BOS versus control (respectively p<0.01 and p<0.05). Complement proteins were exclusively present in rCLAD and correlated positively with immunoglobulins. Additionally, in blood, DSA were more present in rCLAD (p=0.041). MMP-9 levels increased in RAS and BOS versus control (p<0.001) and MMP-9 induced gelatin degradation was only increased in BOS compared to control (p<0.01).
  
  
  
  We demonstrated increased levels of immunoglobulins and complement proteins dominantly present in rCLAD. This leads to the belief that antibodies and AMR might play a more important role in rCLAD compared to BOS. Therefore, anti B-cell therapy could offer beneficial therapeutic effects in patients diagnosed with rCLAD, which needs further research.
authors: Lung Transplant Unit, Division of Respiratory Disease, Department of Clinical and Experimental Medicine, KULeuven, Leuven, Belgium.
authors: Elly
authors: E
authors: Vandermeulen
authors: Lung Transplant Unit, Division of Respiratory Disease, Department of Clinical and Experimental Medicine, KULeuven, Leuven, Belgium.
authors: Stijn E
authors: SE
authors: Verleden
authors: Lung Transplant Unit, Division of Respiratory Disease, Department of Clinical and Experimental Medicine, KULeuven, Leuven, Belgium.
authors: Hannelore
authors: H
authors: Bellon
authors: Lung Transplant Unit, Division of Respiratory Disease, Department of Clinical and Experimental Medicine, KULeuven, Leuven, Belgium.
authors: David
authors: D
authors: Ruttens
authors: Lung Transplant Unit, Division of Respiratory Disease, Department of Clinical and Experimental Medicine, KULeuven, Leuven, Belgium.
authors: Elise
authors: E
authors: Lammertyn
authors: Laboratory of Virology and Chemotherapy (Rega Institute), Department of Microbiology and Immunology, KULeuven, Leuven, Belgium.
authors: Sandra
authors: S
authors: Claes
authors: Laboratory of Immunobiology (Rega Institute), Department of Microbiology and Immunology, KULeuven, Leuven, Belgium.
authors: Jennifer
authors: J
authors: Vandooren
authors: Laboratory of Immunobiology (Rega Institute), Department of Microbiology and Immunology, KULeuven, Leuven, Belgium.
authors: Estafania
authors: E
authors: Ugarte-Berzal
authors: Laboratory of Virology and Chemotherapy (Rega Institute), Department of Microbiology and Immunology, KULeuven, Leuven, Belgium.
authors: Dominique
authors: D
authors: Schols
authors: HILA laboratory, Rode Kruis Vlaanderen, Mechelen, Belgium.
authors: Marie-Paule
authors: MP
authors: Emonds
authors: Lung Transplant Unit, Division of Respiratory Disease, Department of Clinical and Experimental Medicine, KULeuven, Leuven, Belgium.
authors: Dirk E
authors: DE
authors: Van Raemdonck
authors: Laboratory of Immunobiology (Rega Institute), Department of Microbiology and Immunology, KULeuven, Leuven, Belgium.
authors: Ghislain
authors: G
authors: Opdenakker
authors: Lung Transplant Unit, Division of Respiratory Disease, Department of Clinical and Experimental Medicine, KULeuven, Leuven, Belgium.
authors: Geert M
authors: GM
authors: Verleden
authors: Lung Transplant Unit, Division of Respiratory Disease, Department of Clinical and Experimental Medicine, KULeuven, Leuven, Belgium.
authors: Robin
authors: R
authors: Vos
authors: Lung Transplant Unit, Division of Respiratory Disease, Department of Clinical and Experimental Medicine, KULeuven, Leuven, Belgium. Electronic address: bart.vanaudenaerde@med.kuleuven.be.
authors: Bart M
authors: BM
authors: Vanaudenaerde
mesh_terms: D000328:Adult; D056151:Airway Remodeling; D001989:Bronchiolitis Obliterans / Q000175:diagnosis*; D018893:Bronchoalveolar Lavage / Q000379:methods; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology*; D002908:Chronic Disease; D015935:Complement C4b / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D006084:Graft Rejection / Q000175:diagnosis*; D006801:Humans; D056724:Immunity, Humoral; D007136:Immunoglobulins / Q000378:metabolism*; D008168:Lung / Q000378:metabolism / Q000473:pathology*; D016040:Lung Transplantation; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008875:Middle Aged; D010446:Peptide Fragments / Q000378:metabolism*; D010641:Phenotype; D014184:Transplantation, Homologous
chemical_list: D007136:Immunoglobulins; D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d; D020780:Matrix Metalloproteinase 9
keywords: Antibody mediated rejection; Broncho-alveolar lavage fluid; Chronic lung allograft dysfunction