Study of One Protein Implicated in Wegener Disease

Not Applicable

Completed

• Conditions: Wegener's Granulomatosis
• Interventions: Biological: Physiopathology Endpoint Classification

• Registration Number: NCT01167491
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

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.

Study Timeline

• Study Start: 2010-05
• Study First Submitted: 2010-07-12
• Study First Submitted QC: 2010-07-21
• Study First Posted: 2010-07-22
• Primary Completion: 2013-11
• Study Completion: 2014-09
• Status Verified: 2015-04
• Last Update Submitted: 2015-04-20
• Last Update Posted: 2015-04-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 138

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

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Exclusion Criteria

• <18 years
• Pregnancy or breastfeeding
• Absence of signed informed consent
• No affiliation to insurance

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Disease group	Physiopathology Endpoint Classification	Physiopathology

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

Medecine Interne Hôpital Saint Louis; 🇫🇷 Paris, France