Airway factor XIII associates with type 2 inflammation and airway obstruction in asthmatic patients

J Allergy Clin Immunol. 2016 Mar;137(3):767-73.e6. doi: 10.1016/j.jaci.2015.05.053. Epub 2015 Oct 30.

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.

Keywords: Factor XIII; IL-13; air trapping; airway obstruction; allergy; asthma; eosinophils; inflammation; pulmonary function; severe asthma.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Airway Obstruction / metabolism*
  • Airway Obstruction / pathology*
  • Asthma / diagnosis
  • Asthma / genetics*
  • Asthma / pathology*
  • Biomarkers
  • Bronchial Provocation Tests
  • Bronchoalveolar Lavage Fluid
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Factor XIII / genetics*
  • Factor XIII / metabolism
  • Female
  • Gene Expression
  • Humans
  • Immunoglobulin E / blood
  • Immunoglobulin E / immunology
  • Male
  • Middle Aged
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Respiratory Function Tests
  • Severity of Illness Index
  • Skin Tests
  • Young Adult

Substances

  • Biomarkers
  • RNA, Messenger
  • Immunoglobulin E
  • Factor XIII