Neutrophils as Prognostic Factors in Granulomatosis With Polyangiitis (Formerly Named Wegener's Granulomatosis)

NCT01862068 | Completed

• 1 other identifier: NI 10017
• Study Type: observational
• Target: 93
• Locations: 1 country
• Sites: 1

Brief Summary

Anti-neutrophil cytoplasm antibodies (ANCA)-associated vasculitis are rare diseases characterized by inflammation of blood vessels. Among the numerous cell types that play a role in vasculitis, one of the key actors is the neutrophil. Neutrophils are equipped with very powerful molecules that they use to destroy the invading microbes. Therefore, the mechanisms controlling neutrophil activation should be tightly controlled. If that is not the case, neutrophils may destroy the tissues of the host. This is what happens during chronic inflammation in vasculitis. Autoantibodies directed against neutrophils, ANCA, produced thus demonstrating that neutrophils are also targets of the immune system in these diseases. In addition, molecular studies provided evidence that genes normally silenced in mature neutrophils under normal conditions can be re-expressed in neutrophils from patients with ANCA-associated vasculitis thus strongly suggesting a profound deregulation of neutrophil functions in these conditions. Notably, the investigators have preliminary data showing that neutrophils from patients with granulomatosis with polyangiitis (GPA, formerly Wegener's granulomatosis), an ANCA-associated vasculitis, interfere with the normal phase of resolution of inflammation. The objective of the investigators' study is to understand the mechanisms underlying this increased activation state and determine if neutrophils could be used to define prognostic markers by clinicians to optimize patients' care. Therefore, the investigators plan to study the expression of proteins implicated in GPA pathophysiology at the membrane of neutrophils when they undergo apoptosis. The investigators will also study the deregulation of protein expression in neutrophils. This point will be the molecular translation of neutrophil deregulation. This technique is powerful and well adapted to identify by mass spectrometry the proteins that will be differentially expressed between the control and the disease state. After identification of proteins differentially expressed in patients with GPA, the investigators will further investigate whether their expression is modulated during the disease course and/or modified by the treatment. The investigators believe that understanding these neutrophil perturbations can lead to better monitoring of disease activity. Ultimately, the investigators may propose more targeted anti-inflammatory therapies which would be better tolerated by patients. the investigators also can identify new markers for disease activity which allow clinicians to define a better therapeutic strategy.

Conditions

Granulomatosis With Polyangiitis

Keywords

Pronostic factors; Neutrophils; Granulomatosis with polyangiitis; Microscopic polyangiitis; ANCA associated vasculitis; Proteomics

Outcome Measures

Primary Outcomes (1)

• level of neutrophils

  Proteomic analysis of neutrophils compared to healthy donors and MPA (microscopic polyangiitis) patients

  At Day 0

Study Arms (5)

GPA patients

GPA patients with an active disease at inclusion

Other: Blood samples and clinical data

MPA patients

Other: Blood samples and clinical data

Healthy Blood Donors

Other: Blood sample

Atherosclerotic patients

Other: Blood samples and clinical data

EGPA (Eosinophilic Granulomatosis With Polyangiitis)

Other: Blood samples and clinical data

Interventions

Blood samples and clinical data OTHER

Blood samples will be performed at inclusion and at 12 months from all patients (4 groups GPA, MPA, EGPA and Atherosclerotic patients)

Atherosclerotic patients; EGPA (Eosinophilic Granulomatosis With Polyangiitis); GPA patients; MPA patients

Blood sample OTHER

Blood sample will be performed at inclusion from all healthy patients

Healthy Blood Donors

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

GPA (Granulomatosis with polyangiitis) patients and MPA ( Microscopic Polyangiitis) with an active disease at inclusion

You may qualify if:

• For patients with GPA
• Systemic or localized GPA with ACR (American College of Rheumatology) criteria.
• BVAS \> 3.
• ANCA anti-PR3 or anti-MPO
• Consent form signed
• For patients with MPA
• Systemic MPA with Chapel Hill criteria.
• BVAS \> 3.
• ANCA anti-MPO
• Consent form signed
• For patients with EGPA
• Systemic EGPA with ACR (American College of Rheumatology) criteria.
• BVAS \> 3.
• ANCA anti-PR3 or anti-MPO
• Consent form signed

You may not qualify if:

• Pregnancy
• \<18 yr
• Malignancy
• Infectious diseases: HIV, HBV, HCV

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• URC-CIC Paris Descartes Necker Cochin: collaborator

Study Sites (1)

Cochin Hospital

Paris, 75014, France

Location

Related Publications (2)

• Millet A, Martin KR, Bonnefoy F, Saas P, Mocek J, Alkan M, Terrier B, Kerstein A, Tamassia N, Satyanarayanan SK, Ariel A, Ribeil JA, Guillevin L, Cassatella MA, Mueller A, Thieblemont N, Lamprecht P, Mouthon L, Perruche S, Witko-Sarsat V. Proteinase 3 on apoptotic cells disrupts immune silencing in autoimmune vasculitis. J Clin Invest. 2015 Nov 2;125(11):4107-21. doi: 10.1172/JCI78182. Epub 2015 Oct 5.

  PMID: 26436651 BACKGROUND

• Amsler J, Everts-Graber J, Martin KR, Roccabianca A, Lopes C, Tourneur L, Mocek J, Karras A, Naccache JM, Bonnotte B, Samson M, Hanslik T, Puechal X, Terrier B, Guillevin L, Neel A, Mouthon L, Witko-Sarsat V. Dysregulation of neutrophil oxidant production and interleukin-1-related cytokines in granulomatosis with polyangiitis. Rheumatology (Oxford). 2024 Aug 1;63(8):2249-2258. doi: 10.1093/rheumatology/kead578.

  PMID: 37947315 DERIVED

Biospecimen

Retention: SAMPLES WITHOUT DNA

Whole blood

MeSH Terms

Conditions

Granulomatosis with Polyangiitis; Microscopic Polyangiitis; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases; Systemic Vasculitis; Vasculitis; Vascular Diseases; Cardiovascular Diseases; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Cerebral Small Vessel Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 1, 2013
• First Posted: May 24, 2013
• Study Start: May 25, 2012
• Primary Completion: May 18, 2018
• Study Completion: May 18, 2018
• Last Updated: September 12, 2025

Record last verified: 2025-09

Locations

FR (1)