Patient description: A 57-year-old man was admitted to the clinic because of weight loss and persistent dry cough 4 months ago. Chest computed topography showed bilateral multiple infiltrates in the upper lobes and thickened bronchial walls. There is a documented positive serum MPO-ANCA in his medical record. Transbronchial biopsy revealed necrotic granulomas with multinucleated giant cells and the Wegener's granulomatosis was diagnosed for him. He is treating with corticosteroid and cyclophosphamides since 4 months ago. His Birmingham Vasculitis Activity Score (BVAS) is above 4 since the beginning of his disease. His last physical exam and lab study was performed yesterday and showed the results bellow: A wellbeing, well-nourished man, non-icteric, cooperative and alert Weight: 73 kg Height: 177 BP: 120/80 HR: 90/min RR: 22/min Hgb: 13 g/dl WBC: 8000 /mm3 (Neutrophil: 2700/mm3) Plt: 300000 /ml AST: 40 U/L ALT: 56 U/L Alk P: 147 U/L Bill total: 1.2 mg/dl ESR: 120 mm/hr MPO-ANCA: 153 EU

Clinical trial eligibility criteria: eligible ages (years): 18.0-999.0,  Granulomatosis With Polyangiitis (Wegener's Granulomatosis) GPA Specific 1. Patients must have met at least 2 of the 5 modified ACR classification for GPA. These do not need to be present at the time of study entry. The modified ACR are Nasal or oral inflammation, defined as the development of painful or painless oral ulcers or purulent or bloody nasal discharge Abnormal chest radiograph, defined as the presence of nodules, fixed infiltrates, or cavities Active urinary sediment, defined as microscopic hematuria (>5 red blood cells per high power field) or red blood cell casts Granulomatous inflammation on biopsy, defined as histologic changes showing granulomatous inflammation within the wall of an artery or in the perivascular or extravascular area (artery or arteriole) Positive anti-neutrophil cytoplasmic antibody (ANCA) test specific for proteinase-3, measured by enzyme-linked immunoassay 2. Active GPA in the ENT domain within 1 month prior to screening, where the active disease is defined as a score of ≥2 on a GPA ENT disease activity score (7 items scored as 1= present 0= absent) performed by direct endoscopic visualization of the upper airway and audiometric evaluation by a single expert otolaryngologist. Items included in the GPA ENT disease activity score are Bloody rhinorrhea (Daily blood stained nasal discharge) Objective stridor (Stridor assessed by doctor) Inflammation on nasal examination (Ulcers, granulation, friable mucosa on rigid nasendoscopy. Excluding crusting) Inflammation on flexible laryngoscopy (Ulcers, granulation, friable mucosa in the larynx)  Disease-Specific Concerns: 1. Creatinine >4.0mg/dl 2. Respiratory failure requiring mechanical ventilatory support 3. Previous treatment with rituximab (Rituxan® ) within 6 months of screening 4. History of severe allergic or anaphylactic reaction or serious infusion reaction while receiving rituximab 5. Failure to respond to previous course of rituximab (Rituxan®) administered for treatment of GPA, as determined by the discretion of the PI 5. History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies 6. Use of the maintenance immunosuppressive agent (methotrexate, azathioprine, mycophenolate mofetil or leflunomide) within 5 drug half-lives prior to baseline 7. Treatment with any other biologic agent, including belimumab, within the past 3 months of screening 8. Treatment with cyclophosphamide (oral or intravenous) within the past 1 month of screening General Medical Concerns Pregnancy (a negative serum pregnancy test should be performed for all women of childbearing potential within 7 days of treatment), or lactating Inability to comply with study and/or follow-up procedures. Rituximab-Specific Concerns History of HIV Presence of active infection New York Heart Association Classification III or IV heart disease (See Appendix D) Concomitant malignancies or previous malignancies within the last five years, with the exception of adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix History of psychiatric disorder At the Investigator's discretion, receipt of a live vaccine within 4 weeks prior to randomization. Positive hepatitis B or C serology is considered a potential criterion. Hepatitis B screening should hepatitis B surface antigen (HBsAg) and core antibody (anti-HBc) in all patients. For patients who show evidence of prior hepatitis B infection (HBsAg positive [regardless of antibody status] or HBsAg negative but anti-HBc positive), consult with physicians with expertise in managing hepatitis B regarding monitoring and consideration for HBV antiviral therapy before and/or during Rituxan treatment