Genetic Architecture of Neutrophil-Mediated Inflammatory Skin Diseases

Официальное название

Case-Control Study of the Genetic Architecture of Neutrophil-Mediated Inflammatory Skin Diseases

Обзор

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.

Подробное описание

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.

Вмешательства

• Другое Analysis of samples
  DNA extraction from blood or saliva samples for the identification of gene variants by next generation sequencing;
• Другое Analysis of samples
  RNA extraction from blood and skin samples for Nanostring analyses, quantitative RT-PCR or RNA sequencing.
• Другое Analysis of samples
  Biobanked skin samples will be analyzed by immunostaining and imaging techniques to identify cell types in lesions and compare them to healthy skin.
• Другое Analysis of samples
  Cells isolated from biobanked blood and skin samples will be cultured in vitro and proteins will be analyzed by ELISA (secreted proteins) and western blot (cell proteins).

Первичные конечные точки

• Number of protein-coding rare variants associated with forms of NMID [Срок оценки: one time assessment at baseline]

Вторичные конечные точки (5)

• Imaging Mass Cytometry [Срок оценки: one time assessment at baseline]
• RNA expression [Срок оценки: one time assessment at baseline]
• Immune cell count [Срок оценки: one time assessment at baseline]
• Rate of mean fluorescence intensity of immune cells [Срок оценки: one time assessment at baseline]
• Protein quantification (ELISA) [Срок оценки: one time assessment at baseline]

Критерии участия

Критерии включения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Модель наблюдения

Случай-контроль

Центры проведения

Швейцария · 1 центр

• University Hospital Basel, Clinic of Dermatology — Basel

Идентификаторы

NCT: NCT05732987 · 2020-02645; sp19Navarini3

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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