Inflammatory Dermatoses, Neutrophil-mediated Inflammatory Dermatoses
Conditions
Keywords
inflammasome, inflammation-driving pathway, gene variants, next generation sequencing
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.
Interventions
OTHERAnalysis of samples
DNA extraction from blood or saliva samples for the identification of gene variants by next generation sequencing;
Sponsors
University Hospital, Basel, Switzerland
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of protein-coding rare variants associated with forms of NMID | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Imaging Mass Cytometry | 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 |
| RNA expression | 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 |
| Immune cell count | 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 |
| Rate of mean fluorescence intensity of immune cells | 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 |
| Protein quantification (ELISA) | 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) |
Countries
Switzerland
Contacts
Primary ContactAlexander Navarini, Prof. Dr. med.
Backup ContactEmmanuel Contassot, Dr.
Outcome results
None listed