Genetic Architecture of Neutrophil-Mediated Inflammatory Skin Diseases

Official title

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

Overview

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.

Interventions

• Other Analysis of samples
  DNA extraction from blood or saliva samples for the identification of gene variants by next generation sequencing;
• Other Analysis of samples
  RNA extraction from blood and skin samples for Nanostring analyses, quantitative RT-PCR or RNA sequencing.
• Other 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.
• Other 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).

Primary outcome measures

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

Secondary outcome measures (5)

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

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Observational model

Case-control

Study locations

Switzerland · 1 center

• University Hospital Basel, Clinic of Dermatology — Basel

Identifiers

NCT: NCT05732987 · 2020-02645; sp19Navarini3

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗