Dataset Information

Serum protein biomarkers for juvenile dermatomyositis: a pilot study.

ABSTRACT: Background:Blood accessible biomarkers to assess disease activity and their response to therapies in Juvenile Dermatomyositis (JDM) are urgently needed. This pilot study aims to identify serum protein biomarkers associated with clinical disease activity in untreated JDM and their response to medical therapy. Methods:SomaScan® technology screened JDM patients for 1305 proteins at three points: 1) before start of treatment, 2) while on therapy, and 3) after treatment tapering when patients were clinically inactive. To define disease associated biomarkers, SomaScan® data from untreated JDM patients (n?=?8) were compared to SomaScan® data from an independent age-matched healthy control group (n?=?12). Longitudinal analysis defined treatment responsive proteins at three time points: untreated (7 samples), treated (7 samples), and clinically inactive (6 samples). To confirm the SomaScan® data, a subset of nine candidate proteins (CXCL11, IL-17B, IL-17D, IL-22, CXCL10, MCP-1, ANGPT2, MIF, IL-23) were tested by ELISA after adding 2 JDM (one untreated, one clinically inactive) serum samples to the same group of JDM girls (8 untreated, 7 treated; 7 clinically inactive) as well as with 17 age, gender, matched healthy controls. Results:Comparison of untreated JDM versus healthy controls identified 202 elevated and 49 decreased serum proteins in JDM patients with an adjusted p-value

SUBMITTER: Tawalbeh SM

PROVIDER: S-EPMC7528471 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Serum protein biomarkers for juvenile dermatomyositis: a pilot study.

Tawalbeh Shefa M SM Marin Wilfredo W Morgan Gabrielle A GA Dang Utkarsh J UJ Hathout Yetrib Y Pachman Lauren M LM

BMC rheumatology 20201001

<h4>Background</h4>Blood accessible biomarkers to assess disease activity and their response to therapies in Juvenile Dermatomyositis (JDM) are urgently needed. This pilot study aims to identify serum protein biomarkers associated with clinical disease activity in untreated JDM and their response to medical therapy.<h4>Methods</h4>SomaScan® technology screened JDM patients for 1305 proteins at three points: 1) before start of treatment, 2) while on therapy, and 3) after treatment tapering when p ...[more]

PMID: 33015544

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Project description:OBJECTIVE:Objective evaluation of disease activity is challenging in patients with juvenile dermatomyositis (DM) due to a lack of reliable biomarkers, but it is crucial to avoid both under- and overtreatment of patients. Recently, we identified 2 proteins, galectin-9 and CXCL10, whose levels are highly correlated with the extent of juvenile DM disease activity. This study was undertaken to validate galectin-9 and CXCL10 as biomarkers for disease activity in juvenile DM, and to assess their disease specificity and potency in predicting the occurrence of flares. METHODS:Levels of galectin-9 and CXCL10 were measured by multiplex immunoassay in serum samples from 125 unique patients with juvenile DM in 3 international cross-sectional cohorts and a local longitudinal cohort. The disease specificity of both proteins was examined in 50 adult patients with DM or nonspecific myositis (NSM) and 61 patients with other systemic autoimmune diseases. RESULTS:Both cross-sectionally and longitudinally, galectin-9 and CXCL10 outperformed the currently used laboratory marker, creatine kinase (CK), in distinguishing between juvenile DM patients with active disease and those in remission (area under the receiver operating characteristic curve [AUC] 0.86-0.90 for galectin-9 and CXCL10; AUC 0.66-0.68 for CK). The sensitivity and specificity for active disease in juvenile DM was 0.84 and 0.92, respectively, for galectin-9 and 0.87 and 1.00, respectively, for CXCL10. In 10 patients with juvenile DM who experienced a flare and were prospectively followed up, continuously elevated or rising biomarker levels suggested an imminent flare up to several months before the onset of symptoms, even in the absence of elevated CK levels. Galectin-9 and CXCL10 distinguished between active disease and remission in adult patients with DM or NSM (P = 0.0126 for galectin-9 and P < 0.0001 for CXCL10) and were suited for measurement in minimally invasive dried blood spots (healthy controls versus juvenile DM, P = 0.0040 for galectin-9 and P < 0.0001 for CXCL10). CONCLUSION:In this study, galectin-9 and CXCL10 were validated as sensitive and reliable biomarkers for disease activity in juvenile DM. Implementation of these biomarkers into clinical practice as tools to monitor disease activity and guide treatment might facilitate personalized treatment strategies.

Project description:Chronic obstructive pulmonary disease (COPD) impairs physical status and impacts on mental health. This prospective study was designed to assess associations between mental health and systemic biomarkers, and their combined relationship with long-term survival in stable severe COPD.Forty-five patients with severe but stable COPD (forced expiratory volume in 1 s of 29.8 (quartiles: 22.6; 41.4) %predicted) were assessed using the Hospital Anxiety and Depression Scale (HADS), the Patient Health Questionnaire (PHQ), St. George's Respiratory Questionnaire and the State-Trait Anxiety Inventory (STAI). The following serum biomarkers were measured: 25-OH-cholecalciferol, C-reactive protein, erythrocyte sedimentation rate, leucocyte number, serum amyloid-A (SA-A), N-terminal pro-brain natriuretic peptide, troponin I, glycosylated haemoglobin, haemoglobin (Hb), haematocrit (Hc), creatinine and thyroid-stimulating hormone. Patients were followed-up for 36 months. Associations between aspects of mental health and biomarkers, and their utility as predictors of 3-year survival were evaluated by regression analyses.The prevalence of anxiety (HADS-A: 89.9 %), depression (HADS-D: 58.8 %; PHQ: 60.6 %), somatisation (PHQ-15: 81.8 %) and psychosocial stress (PHQ-stress: 60.6 %) was high. There was a significant positive association between the leucocyte count and SA-A level with STAI-trait anxiety (p = 0.03 and p = 0.005, respectively), and between leucocytes and PHQ-stress (p = 0.043). Hb and Hc were significantly negatively associated with HADS-depression (p = 0.041 and p = 0.031, respectively). Univariate Cox regression analyses revealed that leucocyte count (hazard ratio (HR) 2.976, 95 % CI 1.059-8.358; p = 0.038), and stress (HR 4.922, 95 % CI 1.06-22.848; p = 0.042) were linked to long-term survival. In multivariate Cox regression analyses, including known risk factors for survival in COPD, PHQ-stress (HR 45.63, 95 % CI 1.72-1,208.48; p = 0.022) remained significantly associated with survival.In this pilot study different dimensions of mental health were correlated to serum biomarkers, probably reflecting systemic effects of COPD. While leucocyte number and PHQ-stress were associated with long-term survival in univariate analyses, PHQ-stress remained in multivariate analyses as independent prognostic factor.

Dataset Information

Serum protein biomarkers for juvenile dermatomyositis: a pilot study.

Publications

Serum protein biomarkers for juvenile dermatomyositis: a pilot study.

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