Genetic Architecture of Neutrophil-Mediated Inflammatory Skin Diseases
Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age18-100
SponsorUniversity Hospital, Basel, Switzerland
About this trial
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.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
written consent of the participating person
diagnosis of a disease in the NMID form group or proband of the control group
Disqualifiers
Missing informed consent if samples collected after 2014
no diagnosis of NMID
Missing informed consent
Trial 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.
Trial design
Design model
Case-control
Time perspective
Prospective
Treatments tested in this trial
Analysis of samples
Other interventionDNA extraction from blood or saliva samples for the identification of gene variants by next generation sequencing;
Analysis of samples
Other interventionRNA extraction from blood and skin samples for Nanostring analyses, quantitative RT-PCR or RNA sequencing.
Analysis of samples
Other interventionBiobanked 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
Other interventionCells 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).
Treatment groups
3,370 Participants
are divided into 4 treatment groupsGroup A: Biobank- samples from NMID patients1 intervention
Group B: Formalin-fixed and paraffin-embedded (FFPE) samples1 intervention
Group C: Biobank- samples from controls1 intervention
Group D: Fresh skin samples from healthy donors1 intervention
Trial outcomes
Primary outcomes
1
Number of protein-coding rare variants associated with forms of NMID
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
Time frame
one time assessment at baselineSecondary outcomes
1
Imaging Mass Cytometry
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
Time frame
one time assessment at baseline2
RNA expression
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
Time frame
one time assessment at baseline3
Immune cell count
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
Time frame
one time assessment at baseline4
Rate of mean fluorescence intensity of immune cells
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
Time frame
one time assessment at baselineSponsors and contacts
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Source ClinicalTrials.gov