Study of One Protein Implicated in Wegener Disease

Study Overview
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Brief Summary
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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
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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.

Official Title
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Activating Receptors and DAP12 Protein in Wegener's Granulomatosis

Conditions
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Wegener's Granulomatosis

Intervention / Treatment
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* Biological: Physiopathology Endpoint Classification


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Disease group<br>Physiopathology | Biological: Physiopathology Endpoint Classification<br>* Blood samples will be collected during a routine medical visit.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| level of mRNA expression of DAP12 | Measure:level of mRNA expression of DAP12 by RT-PCR in CD4+T cells, macrophages and neutrophils | less than 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| level of expression of DAP 12 downstream signalling proteins | Measure: level of expression of DAP 12 downstream signalling proteins in CD4+ T cells, macrophages and neutrophils | Less than 24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Wegener, CD4+ T cells, DAP12, NKG2D