Interferon Pathway Activation in Monogenic and Non-monogenic Forms of Pediatric SLE With Renal Involvement. Multicenter Observational Study of Biological Samples.
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 60
- 试验地点
- 3
- 主要终点
- Difference between monogenic and non-monogenic forms of cSLE
研究概览
简要总结
Pediatric SLE includes monogenic forms, some of which involve the interferon type I (IFN-I) pathway. The IFN-I pathway is renally active in adult SLE and correlates with the extent of renal damage. In pediatric SLE, and particularly in lupus nephritis, activation of the IFN-I pathway has never been studied, nor is it known whether monogenic forms underlie more pronounced interferon activation.
详细描述
Pediatric systemic lupus erythematosus (SLE) (cSLE), compared with adult SLE, is characterized by a more severe phenotype, with more marked hematologic, neuropsychiatric, and renal changes. Lupus nephritis is a pivotal manifestation of pediatric SLE and an important prognostic factor. It is hypothesized that activation of the interferon pathway is more pronounced in monogenic forms, in which the response to IFN-I represents the primary alteration and likely the main pathogenic mechanism.
This finding may also be relevant in light of the availability of new drugs that selectively target the IFN-I pathway.
Demonstration of IFN-I pathway activation could be used as a diagnostic algorithm in aggressive pediatric forms resistant to immunosuppressive therapy and represent a therapeutic target.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 1 Month 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of SLE arising before the age of majority (until the age of 18 years) according to SLICC and/or EULAR criteria 2019;
- •Clinical, laboratory and/or histologic evidence of renal involvement manifested before the age of 18 years;
- •Signature of informed consent.
排除标准
- •Onset of renal disease after the age of 18 years;
- •SLE secondary to drugs or associated with other diseases such as systemic sclerosis, rheumatoid arthritis, Sjögren's syndrome, and other connectivities.
结局指标
主要结局
Difference between monogenic and non-monogenic forms of cSLE
时间窗: At the enrollment, in case of renal flare, in case of disease remission
Quantification of the IFN-I target genes distinguishing between monogenic and non-monogenic forms.
Evaluation of expression of MXA protein in renal biopsy
时间窗: Biopsy available at enrollment
Evaluation of expression of MXA protein in renal biopsy (by fluorescence microscopy), distinguishing between genetic and non-genetic forms
Evaluation of the proportions of the various WHO histological classes of renal biopsy
时间窗: At the end of the study (24 months after enrollment)
Evaluation of the proportions of the various WHO histological classes of renal biopsy in patients with monogenic and non-monogenic lupus nephritis. Histological diagnosis at renal biopsy: WHO histological pattern, activity index, chronicity index, renal TMA
次要结局
- Phenotype characterization of cSLE(At the onset of the disease, 3, 6, 12, 24 months from the kidney biopsy,)
- Correlation between the clinical phenotype, response to treatment and amplification of the interferon pathway(At the onset of the disease, 3, 6, 12, 24 months from the kidney biopsy,)
研究者
Carmela Errichiello
Principal Investigator
Meyer Children's Hospital IRCCS