Study of One Protein Implicated in Wegener Disease

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Brief Title

Study of One Protein Implicated in Wegener Disease

Official Title

Activating Receptors and DAP12 Protein in Wegener's Granulomatosis

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 Type

Interventional


Primary Outcome

level of mRNA expression of DAP12

Secondary Outcome

 level of expression of DAP 12 downstream signalling proteins

Condition

Wegener's Granulomatosis

Intervention

Physiopathology Endpoint Classification

Study Arms / Comparison Groups

 Disease group
Description:  Physiopathology

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Biological

Estimated Enrollment

138

Start Date

May 2010

Completion Date

September 2014

Primary Completion Date

November 2013

Eligibility Criteria

        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
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

Accepts Healthy Volunteers

Contacts

Mathilde De Menthon,, MD, PhD, , 

Location Countries

France

Location Countries

France

Administrative Informations


NCT ID

NCT01167491

Organization ID

P081238


Responsible Party

Sponsor

Study Sponsor

Assistance Publique - Hôpitaux de Paris


Study Sponsor

Mathilde De Menthon,, MD, PhD, Principal Investigator, Assistance Publique - Hôpitaux de Paris


Verification Date

April 2015