Study of One Protein Implicated in Wegener Disease (DAP12WEGENER)

Assistance Publique - Hôpitaux de Paris

Status: Completed

Conditions: Wegener's Granulomatosis

Treatments: Biological: Physiopathology Endpoint Classification

Study type: Interventional

Funder types: Other

Identifiers

NCT01167491

P081238

Details and patient eligibility

About

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).

Full 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.

Enrollment: 138 patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

138 participants in 1 patient group

Disease group

Other group

Description:

Physiopathology

Treatment:

Biological: Physiopathology Endpoint Classification