Case-Control Study of the Genetic Architecture of Neutrophil-Mediated Inflammatory Skin Diseases
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 3,370
- 试验地点
- 1
- 主要终点
- Number of protein-coding rare variants associated with forms of NMID
研究概览
简要总结
This study is to identify rare, disease-causing mutations of several rare neutrophil dermatoses. To identify associations between NMID and variants in the genome next generation sequencing, mainly whole exome sequencing, will be used. In a second approach the expression level of already known inflammatory proteins in skin samples will be investigated.
详细描述
The origin of rare severe inflammatory skin diseases in dermatology is insufficiently known. They have in common the presence and activation of phagocytes, affect the quality of life through pain and inflammation and disfiguration, and can even be fatal. This study is intended to build on the findings that several of these neutrophil-mediated inflammatory dermatoses (NMID) have a genetic background and to identify rare, disease-causing mutations of several rare neutrophil dermatoses. This non-clinical case-control study is a research project with biological material and health-related data. To identify associations between NMID and variants in the genome next generation sequencing, mainly whole exome sequencing, will be used. In a second approach the expression level of already known inflammatory proteins in skin samples will be investigated. The data are obtained and verified using standardized methods as e.g. Nanostring, RNA sequencing and qRT-polymerase chain reaction (PCR), proteomics assays and immunohistochemistry as well as flow cytometry and imaging mass cytometry, ELISA, and Western Blot.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •written consent of the participating person
- •diagnosis of a disease in the NMID form group or proband of the control group
- •Exclusion Criteria for patients:
- •Missing informed consent if samples collected after 2014
- •no diagnosis of NMID
- •Exclusion Criteria for healthy controls:
- •Missing informed consent
排除标准
- 未提供
结局指标
主要结局
Number of protein-coding rare variants associated with forms of NMID
时间窗: one time assessment at baseline
The primary endpoint consists in the determination of association between newly identified or previously reported rare gene variants and one or more forms of NMIDs. The discovery of such genetic variants will lead to the identification of defective molecular mechanisms involved in abnormal cutaneous immune reactions in these patients: - Statistically significant association between genetic data and NMID * Detection of protein-coding rare variants associated with forms of NMID * Identification of inflammasome activation in different stages of NMID
次要结局
- Rate of mean fluorescence intensity of immune cells(one time assessment at baseline)
- Immune cell count(one time assessment at baseline)
- RNA expression(one time assessment at baseline)
- Imaging Mass Cytometry(one time assessment at baseline)
- Protein quantification (ELISA)(one time assessment at baseline)