Are Sputum High Mobility Group Box 1 and D-Dimer Changes Relevant Markers of Tissue Damage and Fibrinolysis in Cystic Fibrosis?

BACKGROUND/

OBJECTIVES

Cystic fibrosis (CF) is a genetic disease whose hallmarks include chronic inflammation of the airways causing tissue damage with increased levels of alarmins in the respiratory secretions, as well as activation of the coagulation/fibrinolytic systems that are linked to inflammation. However, no information is available about the fibrinolytic system and how fibrinolysis is involved in airway injury. On the road to understanding this issue, we determined levels of two key markers, High Mobility Group Box 1 (HMGB1), an alarmin, and D-dimers, associated with fibrin breakdown and airway inflammation, in the sputum from patients with cystic fibrosis.

METHODS

Sputum samples were collected from 13 individuals with CF and subjected to two different treatment protocols. In the first protocol, the sample was treated with dithiothreitol (DTT) and then centrifuged in order to collect the supernatant (SED). In the second protocol, the sample was centrifuged and the supernatant was obtained (SE). The pellet obtained was treated with DTT and then centrifuged in order to collect the supernatant (SPE). ELISA assays were performed on all samples.

RESULTS

HMGB1 and D-dimer levels were significantly lower in supernatants from sputum centrifuged before DTT treatment (SE) compared to those processed after DTT (SPE and SED). However, no significant difference was observed between SPE and SED samples for both markers. D-dimer levels in SED correlated positively with FEV1 and blood monocyte counts.

CONCLUSIONS

Direct sputum processing with DTT may be a useful procedure for assessing biomarkers of inflammation and fibrinolysis in CF.