Serum levels of interleukins and S100A8/A9 correlate with clinical severity in patients with dermatomyositis-associated interstitial lung disease

Abstract

Background: Dermatomyositis (DM) is a systemic autoimmune inflammatory disorder that affects primarily skin, muscle and lung, frequently associated with interstitial lung disease (ILD). The objective of this study is to investigate the association between serum cytokines and clinical severity in patients with DM-ILD. Methods: Serum samples of 40 DM-ILD patients and 30 healthy controls were collected. Expressions of S100A8/A9 were analyzed by enzyme-linked immunosorbent assay (ELISA) and interleukins were analyzed by cytometric beads array (CBA). Results: Serum IL-4, IL-6 and S100A8/A9 were observably higher in DM-ILD than those in healthy controls ( p = 0.0013, 0.0017 and < 0.0001, respectively). Serum IL-10 level of patients was dramatically lower than that in controls ( p = 0.0001). IL-4 ( r = 0.1171, p = 0.0040), IL-6 ( r = 0.1174, p = 0.0040) and IL-10 ( r = -0.1829, p = 0.0003) were significantly correlated with S100A8/A9 in DM-ILD patients. S100A8/A9 was significantly correlated with high-resolution computed tomography (HRCT) ( r = 0.1642, p = 0.0157) and lung function (DLCO%: r = -0.2066, p = 0.0061, FVC%: r = -0.2156, p = 0.0050). Conclusions: Serum level of S100A8/A9 may be a valuable marker for assessing the clinical severity of DM-ILD patients. Serum IL-4, IL-6 and IL-10 levels were highly correlated with S100A8/A9, so these cytokines may play a synergistic effect on the progression of DM-ILD. Keywords : Dermatomyositis, Interstitial lung disease, S100A8/A9, Interleukin

Expression of S100A9 and KL-6 in common interstitial lung diseases

“…Data related to S100A9 in ILDs is scarce; however, available evidences suggest that S100A9 may be involved in the pathogenesis of IPF [8] . Moreover, serum levels of S100A9 are reported to be elevated in patients with rheumatoid arthritis, systemic lupus erythematosus, scleroderma, vasculitis, lung cancer, etc [12,65–68,16] . Some studies have demonstrated that it can promote atherosclerosis [69] .…”

“…[8] Moreover, serum levels of S100A9 are reported to be elevated in patients with rheumatoid arthritis, systemic lupus erythematosus, scleroderma, vasculitis, lung cancer, etc. [12,[65][66][67][68]16] Some studies have demonstrated that it can promote atherosclerosis. [69] S100A9 is associated with neutrophils in the blood and constitutes approximately 45% of neutrophilic cytoplasmic proteins.…”

“…Among various investigated factors, including Klebs von den Lungen-6 (KL-6), surfactant protein A, surfactant protein D, matrix metallopeptidase 7, CCR-like protein 18, CCR-like protein 13, and S100 calcium binding protein A9 (S100A9), which could be used for diagnosis, risk-stratification, prediction, and monitoring of treatment response of common ILDs, [5–7] S100A9 and KL-6 are thought to be the most promising markers in the differential diagnosis and evaluation of prognosis of ILDs [7,8] . However, their role as biomarkers of ILDs are limited and not unanimous [8–16] …”

“…[7,8] However, their role as biomarkers of ILDs are limited and not unanimous. [8][9][10][11][12][13][14][15][16] KL-6, a glycoprotein, is encoded by the MUC1 gene and expressed on the outer surface of injured and regenerating alveolar epithelial type II cells and airway epithelial cells. The surface expression of KL-6 is induced during the regeneration process of type II pneumocytes, resulting in an increased concentration in bronchoalveolar lavage fluid (BALF).…”

Promising Neutrophil-Associated Biomarkers in Lung Diseases of Patients with Antisynthetase Syndrome and Dermatomyositis

“…Our data suggest that IL-6 was lower in IIM-ILD patients who did not present RP-ILD. There have been many studies on the relationship between IL-6 and IIM; serum IL-6 and immune cell expressions of IL-6 were increased in IIM patients than healthy people [31,32]. Therefore, instead of simply comparing IL-6 with healthy individuals, we specifically studied IL-6 in RP-ILD.…”