Wegener's Granulomatosis
Conditions
Keywords
Wegener, CD4+ T cells, DAP12, NKG2D
Brief summary
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).
Detailed description
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.
Interventions
BIOLOGICALPhysiopathology Endpoint Classification
Blood samples will be collected during a routine medical visit.
Sponsors
Assistance Publique - Hôpitaux de Paris
URC-CIC Paris Descartes Necker Cochin
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Group 1: WG, with granulomatous lesions limited to upper airway or lungs and no evidence of generalized vasculitis ,± biopsy, ± anti-PR3 ANCA * Group 2: WG with granulomatous lesions plus vasculitis expression (renal, neurological, skin, gut or heart involvement), ± biopsy, ± anti-PR3 ANCA * Group 3: Necrotizing vasculitis with no granulomatous lesions, ± PAUCI immune glomerulonephritis, ± anti-MPO ANCA * Group 4: clinical presentation compatible with sarcoidosis, ± biopsy, ± ECA elevated ± tuberculin anergy
Exclusion criteria
* \<18 years * Pregnancy or breastfeeding * Absence of signed informed consent * No affiliation to insurance
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| level of mRNA expression of DAP12 | less than 24 hours | Measure:level of mRNA expression of DAP12 by RT-PCR in CD4+T cells, macrophages and neutrophils |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| level of expression of DAP 12 downstream signalling proteins | Less than 24 hours | Measure: level of expression of DAP 12 downstream signalling proteins in CD4+ T cells, macrophages and neutrophils |
Countries
France
Contacts
PRINCIPAL_INVESTIGATORMathilde De Menthon,, MD, PhD
Assistance Publique Hopitaux de Paris
Outcome results
None listed