Please select the eligibility criteria that correspond to the clinical trial below.
Title: Determining Disease Activity Biomarkers in Individuals With Granulomatosis With Polyangiitis (Wegener's) and Microscopic Polyangiitis
Brief Summary: Granulomatosis with polyangiitis (Wegener's) (GPA) and microscopic polyangiitis (MPA) are two rare immune system disorders that cause the inflammation of blood vessels, or vasculitis. In order to properly treat these diseases, it is critical that the level of disease activity can be determined over the course of the disease. The purpose of this study is to determine new biological markers, or biomarkers, that may be used to assess the severity of disease in people with GPA or MPA.


Options:
A: Inclusion Criteria:

* Documented diagnosis of Wegener's granulomatosis (now called Granulomatosis with Polyangiitis), microscopic polyangiitis or renal limited vasculitis according to Chapel Hill Consensus Conference criteria.
* In stable remission (no documented clinical disease activity) for at least 6 months prior to entry.
* On maintenance immunosuppression with prednisolone, mycophenolate mofetil or azathioprine alone or in combination (maximum 2 agents).
* Documented evidence of CMV infection (CMV-specific immunoglobulin G detected in peripheral blood).
* Documentation that female patients of child bearing potential are not pregnant and using an appropriate form of contraception.
* Written informed consent for study participation

Exclusion Criteria:

* Stage 5 chronic kidney disease (eGFR\<15ml/minute/1.73m2).
* Other significant chronic infection (HIV, HBV, HCV, TB).
* B-cell or T-cell depleting therapy within 12 months.
* Treatment with anti-CMV therapies in last month
* Underlying medical conditions, which in the opinion of the Investigator place the patient at unacceptably high risk for participating in the study.
* Inability to fully or appropriately participate in the study.
B: Inclusion Criteria:

Inclusion (requires all):

* New diagnosis of AASV (WG or MPA) (within the previous six months)
* Active disease (defined by at least one major or three minor BVAS 2003 items, see appendix 1)
* ANCA positivity (c-ANCA and PR3-ANCA or p-ANCA and MPO-ANCA) or histology confirming active vasculitis from any organ (see appendix )
* Written informed consent

Exclusion Criteria:

* Previous treatment with:

  * MMF: more than two weeks ever.
  * Cyclophosphamide: more than two weeks daily oral or more than 1 pulse of IV CYC (15mg/kg)
  * Rituximab or high dose intravenous immunoglobulin within the last twelve months
* Active infection (including hepatitis B, C, HIV and tuberculosis).
* Known hypersensitivity to MMF, AZA or CYC.
* Cancer or an individual history of cancer (other than resected basal cell skin carcinoma).
* Females who are pregnant, breast feeding, or at risk of pregnancy and not using a medically acceptable form of contraception.
* Any condition judged by the investigator that would cause the study to be detrimental to the patient.
* Any other multi-system autoimmune disease including Churg Strauss angiitis, SLE, anti GBM disease and cryoglobulinaemia.
C: Inclusion Criteria:

* Diagnosis of GPA or MPA. Widely accepted diagnostic criteria, as opposed to classification criteria or definitions, have not been developed for GPA and MPA.
* For diagnosis of GPA, meets at least 2 of the following 5 modified American College of Rheumatology (ACR) criteria:

  1. Nasal or oral inflammation with oral ulcers or nasal discharge with pus or blood
  2. Abnormal chest radiograph with nodules, fixed infiltrates, or cavities
  3. Urinary sediment with microhematuria or red cell casts
  4. Granulomatous inflammation within the wall of an artery or in the perivascular area on biopsy
  5. Antineutrophil cytoplasmic antibody (ANCA) positive by enzyme immunoassay for either PR3- or MPO-ANCA
* For diagnosis of MPA, meets the Chapel Hill Consensus Conference Definition for MPA:

  1. Necrotizing vasculitis, with few or no immune deposits, that affects small vessels (i.e., capillaries, venules, arterioles)
  2. Necrotizing arteritis involving small- and medium-sized arteries may be present
  3. Necrotizing glomerulonephritis is very common
  4. Pulmonary capillaritis often occurs
* Parent or guardian willing to provide informed consent, if applicable

Exclusion Criteria:

* Simultaneous diagnoses of both GPA and MPA
* Granulomatosis with polyangiitis (Churg-Strauss)
* Takayasu's arteritis
* Giant cell arteritis
* Polyarteritis nodosa
* Cogan's syndrome
* Behcet's disease
* Sarcoidosis
* Kawasaki disease
* Tuberculosis or any atypical mycobacterial infections
* Deep fungal infections
* Lymphoma, lymphomatoid granulomatosis, or any other type of cancer that mimics anti-neutrophil cytoplasmic antibody-associated vasculitis (AAVs)
* Cryoglobulinemic vasculitis
* Systemic lupus erythematosus
* Rheumatoid arthritis
* Mixed connective tissue disease or any overlapping autoimmune syndrome
D: Inclusion Criteria:

* Patients aged over 18 years-old with newly diagnosed systemic Wegener's granulomatosis,
* microscopic polyangitis with at least one factor of poor prognosis according to the five factors score (proteinuria \> 1 g/day, renal insufficiency defined as a serum creatininemia \> 140 µmol/L, specific cardiomyopathy, gastrointestinal tract and/or CNS involvement).

Exclusion Criteria:

* MPA patients with no poor prognosis factor;
* localized WG;
* relapse of previously known WG or MPA;
* treatment with corticosteroids for more than 1 month prior to diagnosis and start of immunosuppressant;
* co-existence of another multi-system autoimmune disease;
* malignancy (unless considered in complete remission and with no therapy for at least 3 years);
* contra-indication to corticosteroids or study immunosuppressants; pregnancy or no use of contraception in non-menopaused women;
* infection with human immunodeficiency virus; mental or physical disturbances not permitting to give consent.

Answer: C