Genetic Architecture of Neutrophil-Mediated Inflammatory Skin Diseases

NCT ID: NCT05732987

Last Updated: 2023-08-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

3370 participants

Study Classification

OBSERVATIONAL

Study Start Date

2023-02-03

Study Completion Date

2029-09-30

Brief Summary

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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

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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.

Conditions

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Neutrophil-mediated Inflammatory Dermatoses Inflammatory Dermatoses

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

PROSPECTIVE

Study Groups

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Biobank- samples from NMID patients

600 samples from NMID patients from the Biobank Dermatology Unispital Basel (USB) (Biobank USB) and from the biobank of the Dermatology Department of the University Hospital Zürich (USZ) (Biobank USZ) will be included.

Analysis of samples

Intervention Type OTHER

DNA extraction from blood or saliva samples for the identification of gene variants by next generation sequencing;

Analysis of samples

Intervention Type OTHER

RNA extraction from blood and skin samples for Nanostring analyses, quantitative RT-PCR or RNA sequencing.

Analysis of samples

Intervention Type OTHER

Biobanked skin samples will be analyzed by immunostaining and imaging techniques to identify cell types in lesions and compare them to healthy skin.

Analysis of samples

Intervention Type OTHER

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).

Formalin-fixed and paraffin-embedded (FFPE) samples

About 50 of formalin-fixed and paraffin-embedded (FFPE) samples from the Dermatology USB collected before 2014 for RNA and protein expression analyses will be reused. The patients in questions are informed about the study and the coded use of their samples.

Analysis of samples

Intervention Type OTHER

DNA extraction from blood or saliva samples for the identification of gene variants by next generation sequencing;

Analysis of samples

Intervention Type OTHER

RNA extraction from blood and skin samples for Nanostring analyses, quantitative RT-PCR or RNA sequencing.

Analysis of samples

Intervention Type OTHER

Biobanked skin samples will be analyzed by immunostaining and imaging techniques to identify cell types in lesions and compare them to healthy skin.

Analysis of samples

Intervention Type OTHER

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).

Biobank- samples from controls

2'700 anonymized control genomes as well as 150 anonymized control samples for the proteomics approach can be used as control samples from the biobank of the Dermatology Department of the University Hospital Zürich (Biobank Dermatology USZ).

Analysis of samples

Intervention Type OTHER

DNA extraction from blood or saliva samples for the identification of gene variants by next generation sequencing;

Analysis of samples

Intervention Type OTHER

RNA extraction from blood and skin samples for Nanostring analyses, quantitative RT-PCR or RNA sequencing.

Analysis of samples

Intervention Type OTHER

Biobanked skin samples will be analyzed by immunostaining and imaging techniques to identify cell types in lesions and compare them to healthy skin.

Analysis of samples

Intervention Type OTHER

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).

Fresh skin samples from healthy donors

A maximum of 20 fresh skin samples from healthy donors are required per skin location. They will be requested from healthy volunteers after information about the study and receiving the informed consent.

Analysis of samples

Intervention Type OTHER

DNA extraction from blood or saliva samples for the identification of gene variants by next generation sequencing;

Analysis of samples

Intervention Type OTHER

RNA extraction from blood and skin samples for Nanostring analyses, quantitative RT-PCR or RNA sequencing.

Analysis of samples

Intervention Type OTHER

Biobanked skin samples will be analyzed by immunostaining and imaging techniques to identify cell types in lesions and compare them to healthy skin.

Analysis of samples

Intervention Type OTHER

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).

Interventions

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Analysis of samples

DNA extraction from blood or saliva samples for the identification of gene variants by next generation sequencing;

Intervention Type OTHER

Analysis of samples

RNA extraction from blood and skin samples for Nanostring analyses, quantitative RT-PCR or RNA sequencing.

Intervention Type 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.

Intervention Type 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).

Intervention Type OTHER

Eligibility Criteria

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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

* Missing informed consent if samples collected after 2014
* no diagnosis of NMID


* Missing informed consent
Minimum Eligible Age

18 Years

Maximum Eligible Age

100 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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University Hospital, Basel, Switzerland

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Alexander Navarini, Prof. Dr. med.

Role: PRINCIPAL_INVESTIGATOR

University Hospital Basel, Clinic of Dermatology

Locations

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University Hospital Basel, Clinic of Dermatology

Basel, , Switzerland

Site Status RECRUITING

Countries

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Switzerland

Central Contacts

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Alexander Navarini, Prof. Dr. med.

Role: CONTACT

+41 61 265 40 84

Emmanuel Contassot, Dr.

Role: CONTACT

+41 61 328 55 45

Facility Contacts

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Alexander Navarini, Prof. Dr. med.

Role: primary

+41 61 265 40 84

Emmanuel Contassot, Dr.

Role: backup

+41 61 328 55 45

Other Identifiers

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2020-02645; sp19Navarini3

Identifier Type: -

Identifier Source: org_study_id

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