Genetic Architecture of Neutrophil-Mediated Inflammatory Skin Diseases

Recruiting

• Conditions: Neutrophil-mediated Inflammatory Dermatoses; Inflammatory Dermatoses

• Registration Number: NCT05732987
• Lead Sponsor: University Hospital, Basel, Switzerland

Brief Summary

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.

Detailed Description

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.

Study Timeline

• Study First Submitted: 2023-01-30
• Study Start: 2023-02-03
• Study First Submitted QC: 2023-02-08
• Study First Posted: 2023-02-17
• Status Verified: 2023-08
• Last Update Submitted: 2023-08-21
• Last Update Posted: 2023-08-22
• Primary Completion: 2029-09
• Study Completion: 2029-09

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 3370

Inclusion Criteria

• 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

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Number of protein-coding rare variants associated with forms of NMID	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

Secondary Outcome Measures

Name	Time	Method
Rate of mean fluorescence intensity of immune cells	one time assessment at baseline	The secondary endpoint will consist in the determination of consequences at the molecular and cellular levels of gene variants and subsequently encoded proteins in the cutaneous lesions from NMID patients by the measurement of protein interactions and networks, immune cells, cytokines and receptors in forms of NMID by statistically significant association of selected reaction monitoring results including: - Mean fluorescence intensity of immune cells
Immune cell count	one time assessment at baseline	The secondary endpoint will consist in the determination of consequences at the molecular and cellular levels of gene variants and subsequently encoded proteins in the cutaneous lesions from NMID patients by the measurement of protein interactions and networks, immune cells, cytokines and receptors in forms of NMID by statistically significant association of selected reaction monitoring results including: - Immune cell count
RNA expression	one time assessment at baseline	The secondary endpoint will consist in the determination of consequences at the molecular and cellular levels of gene variants and subsequently encoded proteins in the cutaneous lesions from NMID patients by the measurement of protein interactions and networks, immune cells, cytokines and receptors in forms of NMID by statistically significant association of selected reaction monitoring results including: - RNA expression
Imaging Mass Cytometry	one time assessment at baseline	The secondary endpoint will consist in the determination of consequences at the molecular and cellular levels of gene variants and subsequently encoded proteins in the cutaneous lesions from NMID patients by the measurement of protein interactions and networks, immune cells, cytokines and receptors in forms of NMID by statistically significant association of selected reaction monitoring results including: -Imaging Mass Cytometry
Protein quantification (ELISA)	one time assessment at baseline	The secondary endpoint will consist in the determination of consequences at the molecular and cellular levels of gene variants and subsequently encoded proteins in the cutaneous lesions from NMID patients by the measurement of protein interactions and networks, immune cells, cytokines and receptors in forms of NMID by statistically significant association of selected reaction monitoring results including: - Protein quantification (ELISA)

Trial Locations

Locations (1)

University Hospital Basel, Clinic of Dermatology; 🇨🇭 Basel, Switzerland