Molecular Reclassification to Find Clinically Useful Biomarkers for Systemic Autoimmune Diseases: Inception Cohort
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 215
- 试验地点
- 10
- 主要终点
- Gene expression in total blood
研究概览
简要总结
Connective tissue diseases (CTD) or systemic autoimmune diseases (SADs) as they are known today are a group of chronic inflammatory conditions with autoimmune aetiology with few treatment options and difficult diagnosis.Brest team contribute to performe a new classification of the following systemic autoimmune diseases in a European Union's Seventh Framework Programme. The aim of this research consiteis to reclassify the individuals affected by SADs into molecular clusters instead of clinical entities through the determination of molecular profiles using several "Omics" techniques.
详细描述
The overall objective of the PRECISESADS IMI project is to reclassify the individuals affected by SADs into clusters of molecular, instead of clinical entities through the determination of molecular profiles using several "-omics" techniques.
The identification of the clusters relies on a cross sectional (CS) cohort/protocol where 2666 individuals (2000 patients and 666 controls) including a sub-study of 288 deeply characterized individuals (240 patients and 48 controls) are to be recruited.
In parallel a longitudinal inception cohort/protocol will be started in order to further explore the clinical relevance of the identified clusters and their evolution over time.
The objectives of the CS study and sub-study are:
- To identify a systemic taxonomy for patients with SADs by producing the following data in individuals with SADs and controls: genetic, epigenomic, transcriptomic, flow cytometric (from peripheral blood mononuclear cells (PBMCs)), metabolomics and proteomic in plasma and urine, exosome analysis, classical serology (antibodies and autoantibodies), and clinical data.
- To better characterize individual SADs at the omics level.
- To perform clustering analyses to determine the groups of individuals who, differentially from other groups, share specific molecular features (precision medicine).
- A deeper analysis will be done in a substudy of 288 individuals.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •· Aged 18 years or older at the time of consent
- •Diagnosed according to prevailing criteria for one of the following systemic autoimmune diseases (see Annex 2)
- •Rheumatoid arthritis (RA)
- •Scleroderma or systemic sclerosis (SSc)
- •Primary Sjögren's syndrome (SjS)
- •Systemic lupus erythematosus (SLE)
- •Primary antiphospholipid syndrome (PAPS)
- •Mixed Connective Tissue Disease (MCTD)
- •Patients with undifferentiated connective tissue disease (UCTD) for over 1 year and that do not fulfill the diagnosis of any of the above diseases.
- •Signed the informed consent form
排除标准
- •· Patients unable to understand the procedures related to the protocol should not be included. The study is voluntary and patients must be able to give their informed consent.
- •Pregnant women
- •Neonatal lupus
- •Drug-induced lupus
- •Patients whose condition is so serious that they cannot take part in the study
- •Severe nephrotic syndrome with proteinuria >=3,5 g/day
- •Patients with stable doses of steroids >15mg/day for the last 3 months or with IV corticosteroids in the last 3 months
- •Patients under immunosuppressants for the last 3 months prior to recruitment with:
- •Methotrexate ≥25mg/week
- •Azathioprine ≥2.5mg/kg/day
- •Cyclosporine A > 3mg/kg/day
- •Mycophenolate Mofetil > 2gr/day
- •Treatment with cyclophosphamide (any dose or route of administration) or Belimumab in the past 6 months
- •Patients with combined therapy of two or more immunosuppressants
- •Patients on depletative therapy such as Rituximab in the last year
- •Patients receiving experimental
- •Overlap syndromes
结局指标
主要结局
Gene expression in total blood
时间窗: 2 years
Gene expression will be done using commercial gene expression microarrays in total blood from all samples using the RNA Paxgene tube.
Genotyping
时间窗: 2 years
Genotyping will be done using a whole genome array.
Cytokine profile determination
时间窗: 2 years
88 different cytokines will be assessed with Luminex
Flow cytometry analysis to determine cell proportions in the total blood mixture in all individuals.
时间窗: 24 hours
9 optimized panels of antibodies will be used to determine cell subpopulations in peripheral blood (including very minor cell populations).
Metabolite determination
时间窗: 2 years
Metabolite determination in plasma and urine using Nuclear Magnetic Resonance
Exosome isolation from plasma and urine
时间窗: 2 years
set up of the methodology for isolating exosomes in these bodily fluids for gene expression analysis
Gene methylation in total blood
时间窗: 2 years
Methylation analysis will be done using the methylome 450k array using the DNA obtained from total blood. MicroRNA gene expression arrays using total blood.
routine autoantibodies in serum
时间窗: 2 years
set of serum autoantibodies will be determined in a European validated laboratory. Also, they will perform detection of antibodies against small lipid moieties i.e.antiphosphorylcholine),lupus anticoagulant and complement proteins in plasma.
次要结局
未报告次要终点