Clinical trial NCT05732987: Genetic Architecture of Neutrophil-Mediated Inflammatory Skin Diseases
Official title: Case-Control Study of the Genetic Architecture of Neutrophil-Mediated Inflammatory Skin Diseases
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Neutrophil-mediated Inflammatory Dermatoses
Inflammatory Dermatoses
Keywords: inflammasome
inflammation-driving pathway
gene variants
next generation sequencing
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
First posted: 2023-02-17
Enrollment: 3370
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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.

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.

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

Primary outcomes:
measure: Number of protein-coding rare variants associated with forms of NMID
timeFrame: one time assessment at baseline
Secondary outcomes:
measure: Imaging Mass Cytometry
timeFrame: one time assessment at baseline
measure: RNA expression
timeFrame: one time assessment at baseline
measure: Immune cell count
timeFrame: one time assessment at baseline
measure: Rate of mean fluorescence intensity of immune cells
timeFrame: one time assessment at baseline
measure: Protein quantification (ELISA)
timeFrame: one time assessment at baseline
Other outcomes:
Locations:
city: Basel
country: Switzerland
facility: University Hospital Basel, Clinic of Dermatology
Study officials:
affiliation: University Hospital Basel, Clinic of Dermatology
name: Alexander Navarini, Prof. Dr. med.
role: PRINCIPAL_INVESTIGATOR
References: