Clinical and Biological Insights from the University of California San Francisco Prospective and Longitudinal Cohort

Benn, Bryan S.; Lehman, Z; Kidd, Sharon A.; Ho, Melissa; Sun, Sara A.; Ramstein, Joris; Arger, N.; Nguyen, Christine; Su, Robert; Gómez, Antonio; Gelfand, Jeffrey M.; Koth, Laura L.

doi:10.1007/s00408-017-0037-y

Cited by 11 publications

(13 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Sarcoidosis subjects who met established ATS diagnostic criteria [20] were enrolled at any point in their disease course as part of the University of California, San Francisco (UCSF) sarcoidosis cohort as previously described [21]. Healthy control subjects were recruited from the Bay Area community.…”

Section: Study Population and Measurementsmentioning

confidence: 99%

“…Healthy control subjects were recruited from the Bay Area community. Blood samples and clinical data that were collected at study visits and used in these analyses included demographics, date of tissue biopsy, organ involvement assessed by physician review of medical records [21], UCSD "Shortness of Breath" (dyspnea) questionnaire [22][23][24], chest X-ray imaging, clinical laboratory tests, and pulmonary function tests which include forced expiratory volume in 1 second (FEV1) percent predicted (%pred), forced vital capacity (FVC %pred), FEV1/FVC ratio, diffusing capacity for carbon monoxide (DLCO %pred), and total lung capacity (TLC %pred). Immunosuppression use was recorded at each study visit and categorized as a binary variable of use of none or any of the following: oral corticosteroids, methotrexate, azathioprine, colchicine, hydroxycholoroquine, or anti-TNF-α therapy.…”

Section: Study Population and Measurementsmentioning

confidence: 99%

“…Gender, race, and prior tobacco smoking history were similar between the two groups. Table 2 summarizes Scadding stage, immunosuppression history, extra-thoracic organ involvement and pulmonary physiology testing results for sarcoidosis subjects [21]. Two subjects with Scadding stage 0 had prior lung involvement that had radiographically resolved at enrollment, five had abnormal pulmonary function tests, and two had isolated neurologic disease.…”

Section: Characteristics Of Sarcoidosis Subjects and Healthy Controlsmentioning

confidence: 99%

See 2 more Smart Citations

Serum CXCL11 correlates with pulmonary outcomes and disease burden in sarcoidosis

Arger

Woodruff

et al. 2019

Respiratory Medicine

Self Cite

View full text Add to dashboard Cite

Background: Sarcoidosis is a systemic granulomatous disease of unknown etiology that affects the lungs in 90% of patients, but has a wide range of disease manifestations and outcomes including chronic and progressive courses. Noninvasive biomarkers are needed to assess these outcomes and guide decisions for long term monitoring and treatment. Interferon-gamma (IFN-γ)inducible chemotactic cytokines (chemokines), CXCL9, CXCL10 and CXCL11, show promise in this regard because they have been implicated in the pathogenesis of and reflect the burden of granulomatous inflammation. CXCL11 has been reported to have unique functional properties in modulating adaptive immunity in model systems so our goal was to examine serum levels of CXCL11 in relation to clinical outcomes in a heterogeneous cohort of sarcoidosis subjects. Methods: CXCL19, CXCL10, and CXCL11 serum levels were measured in sarcoidosis and healthy subjects using ELISA assay. We determined relationships between CXCL11 and standard clinical inflammatory markers, expression of IFN-γ-related genes in whole blood, organ involvement, dyspnea scores, and measures of pulmonary function. Results: In a cross-sectional analysis of 104 sarcoidosis subjects, serum CXCL11 was significantly elevated compared to 49 healthy controls (p < 0.001). CXCL11 was positively correlated with CXCL9 and CXCL10 (p < 0.001), sedimentation rate (p < 0.01), and mean expression of three IFN-γ-related genes in whole blood (GBP1, STAT1, and STAT2) (p < 0.001). CXCL11 was inversely correlated with FVC %predicted (%pred) and FEV1 %pred and higher levels were associated with higher patient-reported dyspnea scores. We found positive correlations between CXCL11 and number of organs involved. Using survival analyses, we found that

show abstract

Section: Study Population and Measurementsmentioning

confidence: 99%

Section: Study Population and Measurementsmentioning

confidence: 99%

Section: Characteristics Of Sarcoidosis Subjects and Healthy Controlsmentioning

confidence: 99%

See 1 more Smart Citation

Serum CXCL11 correlates with pulmonary outcomes and disease burden in sarcoidosis

Arger

Woodruff

et al. 2019

Respiratory Medicine

Self Cite

View full text Add to dashboard Cite

show abstract

“…We enrolled subjects who met diagnostic criteria for sarcoidosis per guidelines endorsed by the American Thoracic Society (31) as previously described (32). The study design for this cohort did not require individuals to be newly diagnosed to participate.…”

Section: Clinical Cohortmentioning

confidence: 99%

“…At each visit, we performed blood sampling and collected clinical data. These data included: demographics (age, sex, and self-identified race), chest radiography at initial visit, organ involvement at the initial visit (as assessed by physician review of medical records) (32); and pulmonary function tests (PFTs), which included forced expiratory volume in 1 second (FEV1) percent predicted (%pred), forced vital capacity (FVC %pred), diffusing capacity for carbon monoxide (DLCO %pred), and total lung capacity (TLC %pred). 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.…”

Section: Clinical Cohortmentioning

confidence: 99%

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

et al. 2020

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Myocarditis in systemic immune-mediated diseases: Prevalence, characteristics and prognosis. A systematic review

Cheng

Baritussio

Giordani

et al. 2022

Autoimmunity Reviews

View full text Add to dashboard Cite

Clinical and Biological Insights from the University of California San Francisco Prospective and Longitudinal Cohort

Cited by 11 publications

References 35 publications

Serum CXCL11 correlates with pulmonary outcomes and disease burden in sarcoidosis

Serum CXCL11 correlates with pulmonary outcomes and disease burden in sarcoidosis

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

Myocarditis in systemic immune-mediated diseases: Prevalence, characteristics and prognosis. A systematic review

Contact Info

Product

Resources

About