Faculty Collaboration Database

CXCL9 and CXCL10 are differentially associated with systemic organ involvement and pulmonary disease severity in sarcoidosis. Respir Med 2020 Jan;161:105822

Date

11/30/2019

Pubmed ID

31783271

Pubmed Central ID

PMC7028429

DOI

10.1016/j.rmed.2019.105822

Scopus ID

2-s2.0-85075364361 (requires institutional sign-in at Scopus site)   20 Citations

Abstract

BACKGROUND: 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.

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.

Author List

Arger NK, Ho ME, Allen IE, Benn BS, Woodruff PG, Koth LL

MESH terms used to index this publication - Major topics in bold

Adult
Chemokine CXCL10
Chemokine CXCL9
Female
Gene Expression
Genetic Association Studies
Humans
Male
Middle Aged
Sarcoidosis, Pulmonary
Severity of Illness Index