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Study of One Protein Implicated in Wegener Disease (DAP12WEGENER)

This study has been completed.
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris Identifier:
First received: July 12, 2010
Last updated: April 20, 2015
Last verified: April 2015
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).

Condition Intervention
Wegener's Granulomatosis
Biological: Physiopathology Endpoint Classification

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: Activating Receptors and DAP12 Protein in Wegener's Granulomatosis

Resource links provided by NLM:

Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • level of mRNA expression of DAP12 [ Time Frame: less than 24 hours ]
    Measure:level of mRNA expression of DAP12 by RT-PCR in CD4+T cells, macrophages and neutrophils

Secondary Outcome Measures:
  • level of expression of DAP 12 downstream signalling proteins [ Time Frame: Less than 24 hours ]
    Measure: level of expression of DAP 12 downstream signalling proteins in CD4+ T cells, macrophages and neutrophils

Enrollment: 138
Study Start Date: May 2010
Study Completion Date: September 2014
Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Disease group
Biological: Physiopathology Endpoint Classification
Blood samples will be collected during a routine medical visit.

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.

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts 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
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Please refer to this study by its identifier: NCT01167491

Medecine Interne Hôpital Saint Louis
Paris, France, 75010
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Principal Investigator: Mathilde De Menthon,, MD, PhD Assistance Publique - Hôpitaux de Paris
  More Information

Responsible Party: Assistance Publique - Hôpitaux de Paris Identifier: NCT01167491     History of Changes
Other Study ID Numbers: P081238
Study First Received: July 12, 2010
Last Updated: April 20, 2015

Keywords provided by Assistance Publique - Hôpitaux de Paris:
CD4+ T cells

Additional relevant MeSH terms:
Granulomatosis with Polyangiitis
Lung Diseases, Interstitial
Lung Diseases
Respiratory Tract Diseases
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
Systemic Vasculitis
Vascular Diseases
Cardiovascular Diseases
Autoimmune Diseases
Immune System Diseases processed this record on May 23, 2017