Integrative indicators of anti-endotoxin immunity and systemic inflammation in bronchial asthma patients with different inflammatory phenotypes

Abstract

Background. Since the role of endotoxin in induction of broncho-obstructive syndrome is above any doubt today, we focused on the role of anti-endotoxin immunity (AEI) in the formation of different phenotypes of chronic inflammation, which underlie characteristics of the course of asthma.
The aim of this study was to determine the role of humoral and mucosal components of AEI and systemic inflammation in different inflammatory phenotypes in patients with asthma, which could be useful in developing personalized therapy.
Materials and methods. The study included 109 patients with a verified diagnosis of moderate to severe asthma. All patients were divided into 3 groups depending on the type of inflammation in the respiratory tract: Group 1, eosinophilic; Group 2, neutrophilic; and Group 3, mixed granulocytic inflammation. The humoral and mucosal components of endotoxin binding systems were evaluated by levels of specific endotoxin-binding class M, A, and G antibodies (anti-ET IgM, anti-ET IgA, and anti-ET IgG) in peripheral blood and the level of secretory anti-endotoxin IgA in induced sputum. Systemic inflammation was assessed by concentration of C-reactive protein (CRP).
Results. Peripheral blood concentrations of anti-ET IgM and anti-ET IgA were elevated in neutrophilic and mixed inflammatory phenotypes. At the same time, in the eosinophilic inflammatory phenotype, these indexes were not significantly different from the control group. In all groups of patients with asthma, concentrations of anti-ET IgG were similar and remained within the normal range. In all inflammatory phenotypes, concentrations of secretory anti-ET IgA and C-reactive protein were increased within the range of low-intensity inflammation. The highest levels of anti-ET IgA and CRP were found in neutrophilic and mixed inflammatory phenotypes. Levels of secretory anti-ET IgA moderately directly correlated with the relative number of neutrophilic leukocytes in induced sputum (r = 0.469, р < 0.05) and levels of CRP moderately directly correlated with levels of secretory anti-ET IgA (r = 0.427, р < 0.05).
Conclusions. The most pronounced humoral and mucosal response to endotoxin and the intensity of systemic inflammation in neutrophilic and mixed inflammatory phenotypes evidenced a significant role of inhaled endotoxin in the formation of severe asthma. The observed imbalance of humoral and mucosal components in AEI systems supports modern ideas of the pathogenesis of asthma with different inflammatory phenotypes and provides a promising possibility of individualized treatment and control of the disease.