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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| 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. |
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| 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). |
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| 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Analysis of samples | Other | DNA extraction from blood or saliva samples for the identification of gene variants by next generation sequencing; |
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| Measure | Description | Time Frame |
|---|---|---|
| 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
| one time assessment at baseline |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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Inclusion Criteria:
Exclusion Criteria for patients:
Exclusion Criteria for healthy controls:
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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.
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Alexander Navarini, Prof. Dr. med. | Contact | +41 61 265 40 84 | alexander.navarini@usb.ch | |
| Emmanuel Contassot, Dr. | Contact | +41 61 328 55 45 | emmanuel.contassot@usb.ch |
| Name | Affiliation | Role |
|---|---|---|
| Alexander Navarini, Prof. Dr. med. | University Hospital Basel, Clinic of Dermatology | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Hospital Basel, Clinic of Dermatology | Recruiting | Basel | 4031 | Switzerland |
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All samples originating from biobanks or Dermatology USB (fixed tissue) will be returned to origin after finishing of study.
| Analysis of samples | Other | RNA extraction from blood and skin samples for Nanostring analyses, quantitative RT-PCR or RNA sequencing. |
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| Analysis of samples | Other | Biobanked skin samples will be analyzed by immunostaining and imaging techniques to identify cell types in lesions and compare them to healthy skin. |
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| Analysis of samples | 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). |
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| one time assessment at baseline |
| 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 | one time assessment at baseline |
| 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 | one time assessment at baseline |
| 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 | one time assessment at baseline |
| Protein quantification (ELISA) | 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 |