Plasma proteome changes linked to late phase response after inhaled
allergen challenge in asthmatics
Abstract
Background. A subset of individuals with allergic asthma
develops a late phase response (LPR) to inhaled allergens, which is
characterized by a prolonged airway obstruction, airway inflammation and
airway hyperresponsiveness. The aim of this study was to identify
changes in the plasma proteome and circulating hematopoietic progenitor
cells associated with the LPR following an inhaled allergen challenge.
Methods. Serial plasma samples from asthmatics undergoing
inhaled allergen challenge were analyzed by mass spectrometry and
immunosorbent assays. Peripheral blood mononuclear cells were analyzed
by flow cytometry. Mass spectrometry data was analyzed using a linear
regression to model the relationship between airway obstruction during
the LPR and plasma proteome changes. Data from immunosorbent assays was
analyzed using linear mixed models. Results. Out of 396
proteins quantified in plasma, 150 showed a statistically significant
change 23 h post allergen challenge. Among the most upregulated were
three protease inhibitors: alpha-1-antitrypsin, alpha-1-antichymotrypsin
and plasma serine protease inhibitor. Altered levels of 13 proteins were
associated with the LPR, including increased factor XIII A and a
decreased von Willebrand factor. No relationship was found between the
LPR and changes in the proportions of classical, intermediate, and
non-classical monocytes. Conclusions. Allergic reactions to
inhaled allergens in asthmatic subjects was associated with changes in a
large proportion of the measured plasma proteome, whereof protease
inhibitors showed the largest changes, likely to influence the
inflammatory response. Many of the proteins altered in relation to the
LPR are associated with coagulation, highlighting potential mechanistic
targets for future treatments of type-2 asthma.