Searching for Diagnostic/Prognostic Biomarkers in Systemic Lupus Erythematosus (SLE) With Renal Involvement by Proteomic Techniques. A Multicentre Study
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 124
- 试验地点
- 1
- 主要终点
- Number of specific endogenous peptides of each study population to help us differentiate among these by solid phase extraction and mass spectrometry that will be applied to urine samples
研究概览
简要总结
Objective: To search for potential biomarkers obtained by non-invasive methods (24-hour urine collection) that distinguish between patients diagnosed with systemic lupus erythematosus with or without renal involvement, patients with non-autoimmune renal disease and healthy donors.
Lupus nephritis is one of the most common and severe complications of systemic lupus erythematosus, causing from asymptomatic mild proteinuria to rapidly progressive glomerulonephritis with kidney failure. To date, kidney biopsy (an invasive medical procedure with associated risks and complications) is essential for making a definitive diagnosis, assessing the severity of the damage and deciding on the best treatment. In relation to this, the identification of biomarkers using a non-invasive biological sample could help to classify population groups, and this would be a great step forward in the clinical setting.
In this research project, we propose to conduct a case and control study. For this, we will first carefully classify the study groups, using clinical data on patients and by testing a pool of peptides described in the scientific literature in each of the sample groups, using solid phase extraction combined with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Subsequently, we will carry out multivariate principal component analysis on the data collected, and calculate corresponding receiver operating characteristic curves, to enable us to identify the masses corresponding to peptides with potential as biomarkers. We will then use classification algorithms to select sets of masses that would allow us to distinguish the population groups, and generate statistical classifiers for assessing the level of confidence in the model and its subsequent validation.
详细描述
BACKGROUND AND STATUS QUO IN THE FIELD
Systemic lupus erythematosus (SLE) is a systemic, chronic autoimmune disease, affecting connective tissue, and is considered a rare disease by the Spanish Foundation for Rare Diseases (FEDER). Its clinical manifestations are varied, being able to affect most types of tissue and organs especially the skin, joints, blood-forming organs, heart, lung, kidney and nervous system (Galindo, 2008). A complex disease, it has a variable clinical course and prognosis, characterised by alternating periods of remission and exacerbation (flares). For this reason, it is important to establish the prognosis of each patient, as well as develop and validate measures of disease activity and accumulated damage (Irastorza et al., 2012; Galindo, 2008; Cervera, 1993).
The aetiology of SLE is still unknown. As well as a variable production of autoantibodies, genetic and environmental factors may be involved in its pathogenesis. Indeed, it is likely that the involvement of various different pathogenic and aetiological agents explains the biological and clinical heterogeneity observed in patients with the disease.
The incidence of SLE varies with age, sex and ethnic group, and other characteristics of the population under study. In Europe, recent data suggest an incidence of 1.5 cases/100,000 and a prevalence of 122 cases/100,000), while specifically in Spain, the EPISER study found a prevalence of 9 cases/100,000. The disease is known to be more common in Afro-Americans, Hispanics and Asians, and moreover, is more severe in these groups, probably due to a mixture of genetic, economic and cultural factors. The female-to-male sex ratio is around 10:1, though the proportion of cases in females is lower among those with onset occurring during childhood or after 65 years of age. In most patients, signs and symptoms of SLE develop between 15 and 40 years of age, with a mean age of disease onset of 29 to 32 years old (Galindo, 2008; Ruiz-Irastorza et al., 2012).
Between 30 and 50% of patients with SLE develop kidney disease, this being one of the first manifestations in 10% of patients. The most common clinical manifestations include proteinuria, micro-haematuria, urinary casts, kidney failure, and high blood pressure. This condition is associated with higher risks of end-stage renal disease (ESRD) 5 to 10 years after diagnosis and of death (Galindo, 2008; Aran et al., 2008; Ruiz-Irastorza et al., 2012; Sanz, 2014).
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Cross Sectional
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy comparison group (controls)
- •People aged 18 years old and over
- •Negative results in serological tests for hepatitis B and C and HIV
- •No known autoimmune diseases when samples were taken
- •Matched to a patient by age, plus or minus 5 years
- •Willing and able to give informed consent to their participation in the study
- •First comparison group of patients
- •The same characteristics as the control group regarding points a, b, d, and e
- •Diagnosed with SLE, according to the ACR criteria (meeting 4 out of the 11 criteria)
- •No known renal involvement
排除标准
- •People aged under 18 years old
- •Positive results in serological tests for hepatitis B and C and HIV
- •Not to give informed consent to their participation in the study
结局指标
主要结局
Number of specific endogenous peptides of each study population to help us differentiate among these by solid phase extraction and mass spectrometry that will be applied to urine samples
时间窗: 3 year
Solid phase extraction and mass spectrometry will be applied to urine samples to get information about endogenous peptides that will allow the differentiation among above described populations (SLE patients, patients without NL with no autoimmune nephropathy and healthy donors). This may have a direct impact in future early diagnosis, facilitating clinicians to apply a better and more effective treatment.
次要结局
未报告次要终点
研究者
Natalia A. Rivera García
Biology PhD
Hospital de Basurto