Bisyuk Y. Clinical, immunological and pharmacogenetic subtypes of the endotoxin-dependent inflammation in patients with asthma

The thesis is devoted to the research of an anti-endotoxin immunity and polymorphism of genes receptors of CD14 (C-159T) and TLR-4 (Asp299Gly) in patients with different subtypes of asthma. The study included 331 asthma patients. The endotoxin-dependent chronic inflammation in asthma is accompanied by increased concentrations of serum anti-endotoxin antibodies of class M, G; higher level of sCD14 in induced sputum and decreased concentrations of secretory anti-endotoxin immunoglobulin A. The presence of genotype CT + TT (C-159T-CD14) has reduced the risk of asthma in non-atopic, neutrophilic, refractory subtype, but has increased risk in eosinophilic subtype and in patients with infrequent exacerbations. The presence of genotype AG + GG (Asp299Gly-TLR-4) has increased the risk of asthma in atopic, eosinophilic, corticosteroid-sensitive sybtypes and in patients with early onset asthma, reversible obstruction. It was proved that efficacy of inhaled corticosteroids and leukotriene modifiers in asthma depends on Asp299Gly polymorphism of TLR-4.