Study of One Protein Implicated in Wegener Disease (DAP12WEGENER)
The investigators recently showed an abnormal expansion of NK-like CD4+ T cells in Wegener's granulomatosis (WG), mainly in the diffuse vasculitis presentation. These cells expressed an assortment of activating NK cell receptors and their signaling partners, in particular DAP12. The investigators hypothesize that DAP12, or a downstream signaling target of DAP12, is the missing link between the different cell components involved in WG (neutrophils, macrophages, CD4 T cells).
|Study Design:||Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
|Official Title:||Activating Receptors and DAP12 Protein in Wegener's Granulomatosis|
- level of mRNA expression of DAP12 [ Time Frame: less than 24 hours ] [ Designated as safety issue: No ]Measure:level of mRNA expression of DAP12 by RT-PCR in CD4+T cells, macrophages and neutrophils
- level of expression of DAP 12 downstream signalling proteins [ Time Frame: Less than 24 hours ] [ Designated as safety issue: No ]Measure: level of expression of DAP 12 downstream signalling proteins in CD4+ T cells, macrophages and neutrophils
|Study Start Date:||May 2010|
|Estimated Study Completion Date:||June 2014|
|Primary Completion Date:||November 2013 (Final data collection date for primary outcome measure)|
Biological: Physiopathology Endpoint Classification
Blood samples will be collected during a routine medical visit.
Other Name: Physiopathology Endpoint Classification
The investigators will test our hypothesis of "DAP-12 gain-of-function" by quantitative (mRNA and protein) and qualitative (DNA, signaling and cellular activation) analysis of the DAP12 signaling pathway in WG patients with localized (group 1; n=30) or diffuse WG (group 2; n=30) by comparison with patients with micro polyangitis (group 3; n=30), or with sarcoidosis ( group 4; n=30), and healthy blood donors (group 5; n=30). Blood samples will be collected during a routine medical visit. These results may help to design future therapeutic strategies based on modulation of specific intra-cellular pathways involved in the disease.
|Medecine Interne Hôpital Saint Louis|
|Paris, France, 75010|
|Principal Investigator:||Mathilde De Menthon,, MD, PhD||Assistance Publique - Hôpitaux de Paris|