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.
Study Type
OBSERVATIONAL
Enrollment
3,370
DNA extraction from blood or saliva samples for the identification of gene variants by next generation sequencing;
RNA extraction from blood and skin samples for Nanostring analyses, quantitative RT-PCR or RNA sequencing.
Biobanked skin samples will be analyzed by immunostaining and imaging techniques to identify cell types in lesions and compare them to healthy skin.
University Hospital Basel, Clinic of Dermatology
Basel, Switzerland
RECRUITINGNumber 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 baseline
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 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
Time frame: 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
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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).
Time frame: 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
Time frame: 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)
Time frame: one time assessment at baseline