Genetic Architecture of Neutrophil-Mediated Inflammatory Skin Diseases (NEUTROSKIN)

August 21, 2023 updated by: University Hospital, Basel, Switzerland

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Observational

Enrollment (Estimated)

3370

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Switzerland
      • Basel, Switzerland, 4031
        • Recruiting
        • University Hospital Basel, Clinic of Dermatology
        • Principal Investigator:
          • Alexander Navarini, Prof. Dr. med.
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 100 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Sampling Method

Probability Sample

Study Population

The study participants will largely be recruited by a.) prospectively collected biopsies of patients from biobanks or b.) analyzing, contacting, and including/excluding the existing patient population of our clinic (FFPE tissues).

Healthy skin is obtained from patients undergoing plastic surgery at the USB. These patients will be informed and their informed consent obtained before surgery.

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
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.
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).
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.
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).
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).
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).
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.
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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of protein-coding rare variants associated with forms of NMID
Time Frame: 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
one time assessment at baseline

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Imaging Mass Cytometry
Time Frame: 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
one time assessment at baseline
RNA expression
Time Frame: 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
one time assessment at baseline
Immune cell count
Time Frame: 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
one time assessment at baseline
Protein quantification (ELISA)
Time Frame: 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)
one time assessment at baseline
Rate of mean fluorescence intensity of immune cells
Time Frame: 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
one time assessment at baseline

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Basel, Switzerland

Investigators

  • Principal Investigator: Alexander Navarini, Prof. Dr. med., University Hospital Basel, Clinic of Dermatology

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 3, 2023

Primary Completion (Estimated)

September 1, 2029

Study Completion (Estimated)

September 1, 2029

Study Registration Dates

First Submitted

January 30, 2023

First Submitted That Met QC Criteria

February 8, 2023

First Posted (Actual)

February 17, 2023

Study Record Updates

Last Update Posted (Actual)

August 22, 2023

Last Update Submitted That Met QC Criteria

August 21, 2023

Last Verified

August 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2020-02645; sp19Navarini3

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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