Dataset Information

CXCL9 and CXCL10 are differentially associated with systemic organ involvement and pulmonary disease severity in sarcoidosis.

ABSTRACT:

Background

Sarcoidosis is a granulomatous inflammatory disease with limited blood markers to predict outcomes. The interferon-gamma (IFN-?)-inducible chemotactic cytokines (chemokines), CXCL9 and CXCL10, are both increased in sarcoidosis patients, yet they possess important molecular differences. Our study determined if serum chemokines correlated with different aspects of disease severity.

Methods

We measured CXCL9 and CXCL10 serum levels at initial study visits and longitudinally in sarcoidosis subjects using ELISA. We examined these chemokines' relationships with pulmonary and organ involvement outcomes, their gene expression, peripheral blood immune cell populations, and immunosuppression use.

Results

Higher CXCL10 levels negatively correlated with FVC, TLC, and DLCO at subjects' initial visit and when measured repeatedly over two years. CXCL10 also positively correlated with longitudinal respiratory symptom severity. Additionally, for every log₁₀(CXCL10) increase, the risk of longitudinal pulmonary function decline increased 8.8 times over the 5-year study period (95% CI 1.6-50, p = 0.014, log₁₀(CXCL0) range 0.84-2.7). In contrast, CXCL9 levels positively correlated with systemic organ involvement at initial study visit (1.5 additional organs involved for every log₁₀(CXCL9) increase, 95% CI 1.1-2.0, p = 0.022, log₁₀(CXCL9) range 1.3-3.3). CXCL10, not CXCL9, positively correlated with its own blood gene expression and monocyte level. Immunosuppressive treatment was associated with lower levels of both chemokines.

Conclusions

In sarcoidosis subjects, serum CXCL9 levels correlated with systemic organ involvement and CXCL10 levels strongly correlated with respiratory outcomes, which may ultimately prove helpful in clinical management. These differing associations may be due to differences in cellular regulation and tissue origin.

SUBMITTER: Arger NK

PROVIDER: S-EPMC7028429 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Publications

CXCL9 and CXCL10 are differentially associated with systemic organ involvement and pulmonary disease severity in sarcoidosis.

Arger Nicholas K NK Ho Melissa E ME Allen Isabel E IE Benn Bryan S BS Woodruff Prescott G PG Koth Laura L LL

Respiratory medicine 20191120

<h4>Background</h4>Sarcoidosis is a granulomatous inflammatory disease with limited blood markers to predict outcomes. The interferon-gamma (IFN-γ)-inducible chemotactic cytokines (chemokines), CXCL9 and CXCL10, are both increased in sarcoidosis patients, yet they possess important molecular differences. Our study determined if serum chemokines correlated with different aspects of disease severity.<h4>Methods</h4>We measured CXCL9 and CXCL10 serum levels at initial study visits and longitudinall ...[more]

PMID: 31783271

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Project description:IntroductionInterstitial lung disease (ILD) is a heterogeneous group of diseases characterized by varying degrees of lung inflammation and/or fibrosis. We investigated biomarkers to infer whether patients with collagen vascular diseases associated ILD (CVD-ILD) and interstitial pneumonia with autoimmune features (IPAF) benefit from immunosuppressive therapy.Materials and methodsWe retrospectively investigated patients with CVD-ILD, IPAF, and idiopathic pulmonary fibrosis (IPF) between June 2013 and May 2017 at our department. First, we assessed differences in serum and bronchoalveolar lavage fluid (BALF) levels of cytokines between groups. Second, we assessed the associations of patient's clinical variables with serum and BALF levels of those cytokines that were different between groups. Finally, we assessed the associations of diagnosis and response to immunosuppressive therapy with serum levels of those cytokines that were different between groups.ResultsWe included 102 patients (51 with IPF, 35 with IPAF, and 16 with CVD-ILD). Serum and BALF levels of CXCL9, CXCL10, and CXCL11 were significantly elevated in patients with IPAF or CVD-ILD compared with those in patients with IPF. BALF levels of CXCL9 and CXCL10 were correlated with the percentages of lymphocytes and macrophages in BALF. Serum levels of CXCL9 and CXCL10 were correlated with BALF levels. Serum levels of CXCL9, CXCL10, and CXCL11 were correlated C-reactive protein, percent predicted forced vital capacity, alveolar-arterial oxygen difference, and the percentages of lymphocytes and macrophages in BALF. Serum levels of CXCL9, CXCL10, and CXCL11 showed moderate accuracy to distinguish patients with CVD-ILD from those with IPAF and IPF. Pre-treatment serum levels of CXCL9 and CXCL11 showed strong positive correlations with the annual forced vital capacity changes in patients with IPAF and CVD-ILD treated with immunosuppressive drugs.ConclusionsSerum CXCL9, CXCL10, and CXCL11 are potential biomarkers for autoimmune inflammation and predictors of the immunosuppressive therapy responses in ILD with background autoimmunity.

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Dataset Information

CXCL9 and CXCL10 are differentially associated with systemic organ involvement and pulmonary disease severity in sarcoidosis.

Background

Methods

Results

Conclusions

Publications

CXCL9 and CXCL10 are differentially associated with systemic organ involvement and pulmonary disease severity in sarcoidosis.

Similar Datasets

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