Abstract
Soluble molecules of the major histocompatibility complex play an important role in the development of various immune-mediated diseases. However, there is not much information on the participation of these proteins in the pathogenesis of chronic obstructive pulmonary disease (COPD). The aim of our work was to determine the content of soluble molecules of the major histocompatibility complex of classes I and II (sHLA-I and sHLA-II) in the exhaled breath condensate (EBC) and in the blood serum in patients with moderate to severe COPD during the exacerbation and stable phase. We investigated 105 patients (male) with COPD aged 46–67 and 21 healthy nonsmoking volunteers (male) comparable in age. The content of sHLA-I and sHLA-II molecules was studied using ELISA. We found an increase in the level of sHLA-I and sHLA-II molecules in EBC, as well as an enhancement in the serum content of sHLA-II in all the examined COPD patients compared to healthy nonsmoking volunteers. The revealed negative correlation between the serum concentration of sHLA-II and values of FEV1 and FEV1/FVC in all examined patients with COPD gives a possibility to consider the content of these proteins as an additional systemic marker of disease severity. The maximum endobronchial and serum concentrations of sHLA-I and sHLA-II were detected in patients with severe COPD during the exacerbation. The negative associations between the content of these molecules in EBC and serum and the parameters of lung function in patients with severe COPD were established. These findings suggest a pathogenetic role of sHLA-I and sHLA-II molecules in the mechanisms of the development and progression of local and systemic inflammation in COPD.
Highlights
The basis of the pathogenesis of chronic obstructive pulmonary disease (COPD) is a progressive inflammatory process in the respiratory tract defining clinical and functional displays of this disease
We established an increase in the level of sHLAI and sHLA-II molecules in exhaled breath condensate (EBC) as well as an elevated serum level of sHLA-II in all studied patients compared to healthy nonsmoking volunteers
The revealed differences in the content of soluble molecules of the major histocompatibility complex in COPD patients depending on the severity degree and the disease period allow us to consider these proteins as potential biomarkers of activation of local and systemic inflammation and severity of COPD
Summary
The basis of the pathogenesis of COPD is a progressive inflammatory process in the respiratory tract defining clinical and functional displays of this disease. Numerous cells of the immune system are involved in the inflammatory process in this disease An activation of these cells is characterized by producing a large number of mediators, changing of the expression of membrane molecules, and secretion of soluble differentiation molecules into extracellular space [1,2,3]. An important role in the regulation of the immune response belongs to the molecules of the major histocompatibility complex of class I (HLA-I) and class II (HLA-II). These proteins are involved in the interaction of all types of immune cells of the body, recognition of both their own, including modified ones, and foreign cells. Soluble HLA proteins are formed by the proteolytic shedding of membrane proteins and/or by an alternative splicing of matrix RNA
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