CXCL9, CXCL10, and CXCL11; biomarkers of pulmonary inflammation associated with autoimmunity in patients with collagen vascular diseases–associated interstitial lung disease and interstitial pneumonia with autoimmune features

Abstract

Introduction Interstitial 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 methods We 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. Results We 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. Conclusions Serum CXCL9, CXCL10, and CXCL11 are potential biomarkers for autoimmune inflammation and predictors of the immunosuppressive therapy responses in ILD with background autoimmunity.

Relation of inflammatory marker trajectories with frailty and aging in a 20-year longitudinal study

“…While sCD40L was shown in previous studies to possibly have anti-inflammatory roles as discussed above, CXCL11/I-TAC was not, and we would have expected a negative correlation of this marker with lung function because of its pro-inflammatory effect in the IFN γ pathway. Such a negative association was seen in cross-sectionally performed studies in sarcoidosis (Arger et al, 2019) and other lung diseases (Kameda et al, 2020), showing higher levels of CXCL11/I-TAC with lower lung function, which is in contrast with our findings. Further studies are needed to confirm our findings in a community-dwelling population and to explain why in our study this relationship was found only in women.…”

Immunological dysfunction persists for 8 months following initial mild-moderate SARS-CoV-2 infection

“…CXCL9 (MIG-1) and CXCL10 (IP-10) are pro-inflammatory T cell chemoattractants that are expressed by monocytes, endothelial cells, and fibroblasts downstream of interferon-gamma signalling 42 . Upon engagement with their receptor CXCR3, mainly expressed on T cells, they drive naïve CD4+ T cell differentiation into effector Th1 cells, as well as recruiting CD4+ and CD8+ T cells in sites of tissue damage, which has been documented during vascular disease and pulmonary fibrosis 43,44 . Both chemokines have been implicated in symptomatic acute coronavirus infections, including COVID-19, where levels were higher in severe compared to asymptomatic subjects 45 , consistent with our data.…”

Natural history and screening of interstitial lung disease in systemic autoimmune rheumatic disorders

“…In addition, higher levels of SP-A and KL-6 predicted severe decline in pulmonary function. 154 In addition, Kameda and colleagues 155 demonstrated that serum and BAL levels of CXCL9, CXCL10 and CXCL11 were significantly increased in patients with IPAF and CTD-ILD compared to IPF. Further studies are needed to validate the clinical significance of these novel biomarkers before becoming part of routine clinical assessment of patients with IPAF.…”