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Project description:BackgroundSystemic sclerosis (SSc) is a multiple-organ disease characterized by vascular damage, autoimmunity, and tissue fibrosis. Organ injuries such as interstitial lung diseases (ILD), resulting from inflammatory and fibrosis processes, lead to poor prognosis. Although autoantibodies are detected in the serum of patients with SSc, the mechanisms by which immune cells are involved in tissue inflammation and fibrosis is not fully understood. Recent studies have revealed carcinoembryonic antigen related cell adhesion molecule (CEACAM)-positive monocytes are involved in murine bleomycin-induced lung fibrosis. We investigated CEACAM-positive monocytes in patients with SSc to clarify the role of monocytes in the pathogenesis of SSc.MethodsThe proportion of of CEACAM-positive classical monocytes in healthy controls (HCs) and patients with rheumatoid arthritis (RA) and SSc was evaluated using flow cytometry. The correlation between the proportion of CEACAM-positive monocytes and clinical parameters was analyzed in patients with SSc. Gene expression microarrays were performed in CEACAM-positive and negative monocytes in patients with SSc. Infiltration of CEACAM-positive monocytes into scleroderma skin was evaluated by immunohistochemical staining.ResultsThe proportion of CEACAM-positive classical monocytes was increased in patients with early SSc within 2 years after diagnosis, which positively correlated with ESR, serum IgG, and serum KL-6 and negatively correlated with %forced vital capacity. The percentage of CEACAM-positive monocytes decreased after immunosuppressive therapy. CEACAM6-positive cells among classical monocytes were significantly increased in patients with SSc compared with HCs and patients with rheumatoid arthritis. SSc serum induced CEACAM6 expression on monocytes from HCs. Functionally, CEACAM-positive monocytes produced higher levels of TNF-α and IL-1β compared to CEACAM-negative cells and showed activation of the NF-κB pathway. Furthermore, CEACAM6-positive monocytes infiltrated the dermis of SSc.ConclusionsCEACAM-positive monocytes showed inflammatory phenotypes and may be involved in the tissue inflammation and fibrosis in early SSc. CEACAM-positive monocytes may be one of biomarkers to detect patients with progressive ILD, requiring therapeutic intervention.
| S-EPMC9632165 | biostudies-literature
Project description:To clarify the characteristics of CEACAM-positive monocytes in systemic sclerosis (SSc), we performed gene expression microarrays between CEACAM-positive and CEACAM-negative classical monocytes from diffused cutaneous systemic sclerosis(dcSSc) patients. We further analyzed expression levels of each subtype of CEACAM on monocytes from dcSSc by flow cytometry and performed gene expression microarrays between CEACAM1+CEACAM6- and CEACAM1-CEACAM6+ monocytes.
2022-08-29 | GSE207424 | GEO
Project description:To clarify the characteristics of CEACAM-positive monocytes in systemic sclerosis (SSc), we performed gene expression microarrays between CEACAM-positive and CEACAM-negative classical monocytes from diffused cutaneous systemic sclerosis(dcSSc) patients. We further analyzed expression levels of each subtype of CEACAM on monocytes from dcSSc by flow cytometry and performed gene expression microarrays between CEACAM1+CEACAM6- and CEACAM1-CEACAM6+ monocytes.
2022-08-29 | GSE207423 | GEO
Project description:CEACAM 1, 3, 5 and 6 -positive classical monocytes correlate with interstitial lung disease in early systemic sclerosis
| PRJNA855448 | ENA
Project description:CEACAM 1, 3, 5 and 6 -positive classical monocytes correlate with interstitial lung disease in early systemic sclerosis
| PRJNA855449 | ENA
Project description:CEACAM 1, 3, 5 and 6 -positive classical monocytes correlate with interstitial lung disease in early systemic sclerosis
| PRJNA855450 | ENA
Project description:ObjectiveTocilizumab (TCZ) has demonstrated lung function preservation in 2 randomized controlled trials in early systemic sclerosis (SSc). This effect has yet to be characterized in terms of radiographically evident quantitative lung involvement. We undertook this study to assess the impact of TCZ on lung function preservation in a post hoc analysis, stratifying treatment arms according to the degree of lung involvement.MethodsThe focuSSced trial was a phase III randomized placebo-controlled trial of TCZ in patients with SSc and progressive skin disease. Participants underwent baseline and serial spirometry along with high-resolution chest computed tomography at baseline and at week 48. Quantitative interstitial lung disease (QILD) and fibrosis scores were assessed by computer software. We classified QILD into the following categories of lung involvement: mild (>5-10%), moderate (>10-20%), and severe (>20%).ResultsOf 210 participants recruited for the trial, 136 patients (65%) had ILD. The majority of these patients (77%) had moderate-to-severe involvement (defined as >10% lung involvement). The TCZ arm demonstrated preservation of forced vital capacity percent predicted (FVC%) over 48 weeks (least squares mean change in FVC% = -0.1) compared to placebo (-6.3%). For mild, moderate, and severe QILD, the mean ± SD change in FVC% in the TCZ arm at 48 weeks were -4.1 ± 2.5% (n = 11), 0.7 ± 1.9% (n =19), and 2.1 ± 1.6% (n = 26), respectively, and in the placebo group were -10.0 ± 2.6% (n = 11), -5.7 ± 1.6% (n = 26), and -6.7 ± 2.0% (n = 16), respectively. Similar treatment-related preservation findings were seen independent of fibrosis severity.ConclusionTCZ in early SSc-associated ILD with progressive skin disease stabilized FVC% over 48 weeks, independent of the extent of radiographically evident QILD.
| S-EPMC8238790 | biostudies-literature
Project description:Systemic sclerosis (SSc) is a progressive and often devastating disease characterized by autoimmune dysfunction, vasculopathy, and fibrosis. Interstitial lung disease (ILD) is identified in the majority of patients with SSc and is the leading cause of SSc-related mortality. Although clinical manifestations and ILD severity vary among patients, lung function typically declines to the greatest extent during the first 3-4 years after disease onset. We aim to provide an overview of SSc-associated ILD (SSc-ILD) with a focus on current and emerging tools for early diagnosis of ILD and current and novel treatments under investigation. Early detection of ILD provides the opportunity for early therapeutic intervention, which could improve patient outcomes. Thoracic high-resolution computed tomography is the most effective method of identifying ILD in patients with SSc; it enables detection of mild lung abnormalities and plays an important role in monitoring disease progression. Cyclophosphamide and mycophenolate mofetil are the most commonly prescribed treatments for SSc-ILD. Recently, nintedanib (an antifibrotic) was approved by the Food and Drug Administration for patients with SSc-ILD; it is indicated for slowing the rate of decline in pulmonary function. However, there is a need for additional effective and well-tolerated disease-modifying therapy. Ongoing studies are evaluating other antifibrotics and novel agents. We envision that early detection of lung involvement, combined with the emergence and integration of novel therapies, will lead to improved outcomes in patients with SSc-ILD.
| S-EPMC6910104 | biostudies-literature
Project description:Purpose of reviewThis review provides an overview of the current treatments for systemic sclerosis-interstitial lung disease (SSc-ILD) and proposes a conceptual framework for disease management with case scenarios.Recent findingsBroad treatment categories include traditional cytotoxic therapies, biologic disease-modifying rheumatic drugs, antifibrotic agents, autologous hematopoietic stem cell transplant, and lung transplantation. The optimal use of each option varies depending on SSc-ILD severity, progression, and comorbidities of individual patients. A high-quality randomized controlled trial demonstrated nintedanib's ability to retard decline of lung function in patients with limited and diffuse cutaneous disease, with established ILD. Tocilizumab, recently approved by the FDA, provides a unique intervention in those with early SSc associated with ILD with elevated acute-phase reactants: two well designed trials showed lung function preservation in phase 2 and phase 3 trials.SummaryStratifying patients based on key SSc-ILD characteristics (e.g. severity, risk of progression, comorbid disease presentation) may provide a useful guide for practitioners treating SSc-ILD.
| S-EPMC8021460 | biostudies-literature
Project description:Although scleroderma-associated interstitial lung disease (SSc-ILD) is a significant contributor to both morbidity and mortality, its pathogenesis is largely unclear. Pulmonary function tests and high-resolution computed tomographic scanning continue to be the most effective tools to screen for lung involvement and to monitor for disease progression. More research and better biomarkers are needed to identify patients most at risk for developing SSc-ILD as well as to recognize which of these patients will progress to more severe disease. Although immunosuppression remains the mainstay of treatment, antifibrotic agents may offer new avenues of treatment for patients with SSc-ILD in the future.
| S-EPMC4515778 | biostudies-literature