Serum CXCL11 correlates with pulmonary outcomes and disease burden in sarcoidosis

Arger, N.; Ho, Melissa; Woodruff, Prescott G.; Koth, Laura L.

doi:10.1016/j.rmed.2019.04.005

Cited by 35 publications

(41 citation statements)

References 43 publications

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“…Studies shown that CXCL11 increases in the serum of patients with SARC as compared to that in healthy controls. Moreover, serum CXCL11 correlates with the severity of symptoms in patients with SARC, specifically organ involvement, respiratory symptoms, and abnormalities in pulmonary function [ 37 ]. Thus, CXCL11 may also be useful in identifying patients at risk for rapid pulmonary dysfunction.…”

Section: Discussionmentioning

confidence: 99%

Identification of Biomarkers for Sarcoidosis and Tuberculosis of the Lung Using Systematic and Integrated Analysis

Zhao

Jin

et al. 2020

Med Sci Monit

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Background Sarcoidosis (SARC) is a multisystem inflammatory disease of unknown etiology and pulmonary tuberculosis (PTB) is caused by Mycobacterium tuberculosis. Both of these diseases affect lungs and lymph nodes and share similar clinical manifestations. However, the underlying mechanisms for the similarities and differences in genetic characteristics of SARC and PTB remain unclear. Material/Methods Three datasets (GSE16538, GSE20050, and GSE19314) were retrieved from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) in SARC and PTB were identified using GEO2R online analyzer and Venn diagram software. Functional enrichment analysis was performed using Database for Annotation, Visualization and Integrated Discovery (DAVID) and R packages. Two protein–protein interaction (PPI) networks were constructed using Search Tool for the Retrieval of Interacting Genes database, and module analysis was performed using Cytoscape. Hub genes were identified using area under the receiver operating characteristic curve analysis. Results We identified 228 DEGs, including 56 common SARC-PTB DEGs (enriched in interferon-gamma-mediated signaling, response to gamma radiation, and immune response) and 172 SARC-only DEGs (enriched in immune response, cellular calcium ion homeostasis, and dendritic cell chemotaxis). Potential biomarkers for SARC included CBX5 , BCL11B , and GPR18 . Conclusions We identified potential biomarkers that can be used as candidates for diagnosis and/or treatment of patients with SARC.

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Section: Discussionmentioning

confidence: 99%

Identification of Biomarkers for Sarcoidosis and Tuberculosis of the Lung Using Systematic and Integrated Analysis

Zhao

Jin

et al. 2020

Med Sci Monit

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“…In our cohort, the median and 25th percentile of FVC is 88% predicted and 72% predicted, findings similar to ACCESS. Similar results were also seen for FEV1, and obstructive changes were common with an FEV1/FVC ratio of < 70% in more than [27,28]. Lung volumes or formal cardiopulmonary exercise testing (CPET) is not routinely used nor is a standard of care in sarcoidosis clinical practice or research as it is more invasive, expensive and normal in many [29].…”

Section: Discussionmentioning

confidence: 70%

Clinical characteristics and organ system involvement in sarcoidosis: comparison of the University of Minnesota Cohort with other cohorts

Perlman

Shenoy

et al. 2020

BMC Pulm Med

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Background: Sarcoidosis is a systemic granulomatous disease of unknown etiology. Clinical cohort studies of different populations are important to understand the high variability in clinical presentation and disease course of sarcoidosis. The aim of the study is to evaluate clinical characteristics, including organ involvement, pulmonary function tests, and laboratory parameters, in a sarcoidosis cohort at the University of Minnesota. We compare the organ system involvement of this cohort with other available cohorts. Methods: We conducted a retrospective data collection and analysis of 187 subjects with biopsy-proven sarcoidosis seen at a tertiary center. Organ system involvement was determined using the WASOG sarcoidosis organ assessment instrument. Clinical phenotype groups were classified using the Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis criteria. Results: Mean subject age at diagnosis was 45.8 ± 12.4, with a higher proportion of males (55.1%), and a higher proportion of blacks (17.1%) compared to the racial distribution of Minnesota residents (5.95%). The majority (71.1%) of subjects required anti-inflammatory therapy for at least 1 month. Compared to the A Case Control Etiologic Study of Sarcoidosis cohort, there was a higher frequency of extra-thoracic lymph node (34.2% vs. 15.2%), eye (20.9% vs. 11.8%), liver (17.6% vs. 11.5%), spleen (20.9% vs. 6.7%), musculoskeletal (9.6% vs. 0.5%), and cardiac (10.7% vs. 2.3%) involvement in our cohort. A multisystem disease with at least five different organs involved was identified in 13.4% of subjects. A restrictive physiological pattern was observed in 21.6% of subjects, followed by an obstructive pattern in 17.3% and mixed obstructive and restrictive pattern in 2.2%. Almost half (49.2%) were Scadding stages II/III. Commonly employed disease activity markers, including soluble interleukin-2 receptor and angiotensin-converting enzyme, did not differ between treated and untreated groups.

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“…We used Pearson correlation analyses to determine the association between T-bet + frequencies of RORγt + Th17.0 cells and previously measured blood markers related to IFN-γ, including serum levels of the IFN-γ-induced chemokines of CXCL9, CXCL10, and CXCL11 (34,35) as well whole blood RNA transcript levels for IFN-γ-related genes (33). We also used linear regression models to adjust for potential confounders.…”

Section: Discussionmentioning

confidence: 99%

“…We obtained immunosuppression use history, including dosages of oral corticosteroids or disease-modifying antirheumatic drugs (DMARDs), specifically, methotrexate, azathioprine, mycophenolate, colchicine, hydroxychloroquine, or anti-TNF-α therapy that subjects were actively taking at the time of their study visits. For the current analysis, we also included serum protein (chemokine levels for CXCL9, CXCL10, and CXCL11) and whole blood RNA transcript levels of IFN-γrelated genes that were measured in the same blood samples as previously described (33)(34)(35).…”

Section: Clinical Cohortmentioning

confidence: 99%

“…To assess if T-bet expression in RORγt + Th17.0 cells was associated with other markers of IFN-γ-related inflammation, we determined the correlations between these T-bet + frequencies and serum levels of IFN-γ-induced chemokines and whole blood gene transcript levels of IFN-γ-related genes, which we had previously measured in the same blood samples (33)(34)(35). We found that the T-bet + frequencies positively correlated with all three serum chemokines (CXCL9, CXCL10, and CXCL11) in models adjusted for age, race, sex, and immunosuppression use ( Table 4).…”

Section: Correlations Between the T-bet + Frequencies Of Rorγt + Th17mentioning

confidence: 99%

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T-bet Expression in Peripheral Th17.0 Cells Is Associated With Pulmonary Function Changes in Sarcoidosis

et al. 2020

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Background: Interferon-gamma (IFN-γ) is a key mediator of sarcoidosis-related granulomatous inflammation. Previous findings of IFN-γ-producing Th17 cells in bronchoalveolar lavage fluid from sarcoidosis patients invokes the transition of Th17.0 cells to Th17.1 cells in the disease's pathogenesis. Since the T-bet transcription factor is crucial for this transition, the goal of this study was to determine if T-bet expression in Th17.0 cells reflects the extent of granulomatous inflammation in sarcoidosis patients as assessed by clinical outcomes. Methods: Using a case-control study design, we identified two groups of sarcoidosis subjects (total N = 43) with pulmonary function tests (PFTs) that either (1) changed (increased or decreased) longitudinally or (2) were stable. We used flow cytometry to measure the transcription factors T-bet and RORγt in Th1, Th17.0, and Th17.1 cell subsets defined by CCR6, CCR4 and CXCR3 in blood samples. We compared the percentages of T-bet + cells in RORγt + Th17.0 cells (defined as CCR6 + CCR4 + CXCR3 −) based on subjects' PFT group. We also assessed the relationship between the direction of change in PFTs with the changes in %T-bet + frequencies using mixed effects modeling. Results: We found that T-bet expression in subjects' RORγt + Th17.0 cells varied based on clinical outcome. The T-bet + percentage of RORγt + Th17.0 cells was higher in the cases (subject group with PFT changes) as compared to controls (stable group) (27 vs. 16%, p = 0.0040). In comparisons before and after subjects' PFT changes, the T-bet + frequency of RORγt + Th17.0 cells increased or decreased in the opposite direction of the PFT change. The percentage of these T-bet + cells was also higher in those with greater numbers of involved organs. Serum levels of interferon-γ-induced chemokines, CXCL9, CXCL10, and CXCL11, and whole blood gene expression of IFN-γ-related genes including GBP1, TAP1, and JAK2 were independently positively associated with the T-bet + frequencies of RORγt + Th17.0 cells. Conclusions: These data suggest that expression of T-bet in Th17.0 cells could reflect the extent of granulomatous inflammation in sarcoidosis patients because they represent a transition state leading to the Th17.1 cell phenotype. These findings indicate that Th17 plasticity may be part of the disease paradigm.

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Serum CXCL11 correlates with pulmonary outcomes and disease burden in sarcoidosis

Cited by 35 publications

References 43 publications

Identification of Biomarkers for Sarcoidosis and Tuberculosis of the Lung Using Systematic and Integrated Analysis

Identification of Biomarkers for Sarcoidosis and Tuberculosis of the Lung Using Systematic and Integrated Analysis

Clinical characteristics and organ system involvement in sarcoidosis: comparison of the University of Minnesota Cohort with other cohorts

T-bet Expression in Peripheral Th17.0 Cells Is Associated With Pulmonary Function Changes in Sarcoidosis

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