title: Airway factor XIII associates with type 2 inflammation and airway obstruction in asthmatic patients.
abstract: BACKGROUND
  Coagulation Factor XIII (FXIII) plays an important role in wound healing by stabilizing fibrin clots and cross-linking extracellular matrix proteins. FXIII is expressed in cells of the monocyte/macrophage and dendritic cell lineages in response to type 2 cytokines.
  
  
  OBJECTIVE
  We sought to determine the association between FXIII and asthma pathobiology.
  
  
  METHODS
  We analyzed the expression of FXIII mRNA and protein levels in bronchoalveolar lavage samples obtained before and after segmental allergen challenge from patients with mild asthma and in induced sputum samples collected from patients with mild-to-moderate and severe asthma.
  
  
  RESULTS
  FXIII mRNA and protein levels were highly upregulated in bronchoalveolar cells and fluid after allergen challenge and mRNA levels correlated with protein levels. In sputum of asthmatic patients, FXIII expression was positively correlated with type 2 immune response and dendritic cell markers (CD209 and CD207). FXIII expression was also associated with increased airflow limitation (FEV1/forced vital capacity and residual volume/total lung capacity ratios) and greater reversibility to β-agonists.
  
  
  CONCLUSIONS
  FXIII expression was upregulated in the airways of asthmatic patients after allergen exposure. Expression in the sputum of asthmatic patients correlated with the type 2 immune response and airflow limitation. Excessive activity of FXIII could contribute to the pathophysiology of airway obstruction in asthmatic patients.
authors.affiliation: Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wis.
authors.forename: Stephane
authors.initials: S
authors.lastname: Esnault
authors.affiliation: Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wis.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Kelly
authors.affiliation: School of Pharmacy, University of Wisconsin School of Medicine and Public Health, Madison, Wis.
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Sorkness
authors.affiliation: Department of Biostatistics and Medical Informatics, University of Wisconsin School of Medicine and Public Health, Madison, Wis.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Evans
authors.affiliation: Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wis.
authors.forename: William W
authors.initials: WW
authors.lastname: Busse
authors.affiliation: Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wis. Electronic address: nnj@medicine.wisc.edu.
authors.forename: Nizar N
authors.initials: NN
authors.lastname: Jarjour
mesh_terms: D000328:Adult; D000402:Airway Obstruction / Q000378:metabolism* / Q000473:pathology*; D001249:Asthma / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D015415:Biomarkers; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D005176:Factor XIII / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012129:Respiratory Function Tests; D012720:Severity of Illness Index; D012882:Skin Tests; D055815:Young Adult
chemical_list: D015415:Biomarkers; D012333:RNA, Messenger; D007073:Immunoglobulin E; D005176:Factor XIII
keywords: Factor XIII; IL-13; air trapping; airway obstruction; allergy; asthma; eosinophils; inflammation; pulmonary function; severe asthma