Soluble HLA-I and HLA-II Molecules Are Potential Prognostic Markers of Progression of Systemic and Local Inflammation in Patients with COPD

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.

De novo discovery of traits co-occurring with chronic obstructive pulmonary disease

“…We also identified several COPD-associated genes enriched for immune processes and immune-related diseases (e.g., HLA-C and HLA-DQB1-antigen processing and presentation, HLA-DQB1-type I diabetes mellitus, influenza A, autoimmune thyroid disease) (Table S5). This finding is consistent with observations that proteins of the major histocompatibility complex of classes I and II (HLA-I and HLA-II) have been identified as potential markers of progression of systemic and local inflammation in patients with COPD (Kubysheva et al, 2018). Specifically, an increase in the level of HLA-I and HLA-II molecules in the exhaled breath condensate as well as an elevated serum level of HLA-II is observed in COPD patients when compared with healthy volunteers (Kubysheva et al, 2018).…”

The Potential of Soluble Human Leukocyte Antigen Molecules for Early Cancer Detection and Therapeutic Vaccine Design

“…Since their discovery, many have tried to find explanations for the altered sHLA levels in malignancies and their association with disease progression and prognosis. In addition to malignancies, altered sHLA levels have been observed in chronic disease [ 82 ], autoimmunity [ 83 , 84 ], and viral infections [ 85 , 86 ]; strongly suggesting that there are shared inflammatory pathways that regulate sHLA. Knowing how sHLA-I and sHLA-II release is regulated and to what extent these complexes affect immune responses is crucial to determine whether their increased presence is merely a consequence of ongoing immunity or whether they also partake in pathophysiological processes.…”

Alveolar epithelial cells are competent producers of interstitial extracellular matrix with disease relevant plasticity in a human in vitro 3D model

“…The only COPD related statistically signi cant difference in the MS analysis was an upregulation of HLA-A. Increased HLA-A protein have previously been found in exhaled breathe condensate of COPD patients, another study found increased gene expression in both AEC2 and in blood samples of COPD patients 44,45 . Our results both support HLA-A as a potential COPD biomarker and indicate that the AEC2 retain characteristics of their origin in this culture system.…”