In the maintenance group, the model was constructed with a random patient-specific intercept and random time effect. in 4.6% of patients, all of whom were in the lowest baseline IgG quartile. Serious infections during maintenance occurred at a rate of 0.85 [95% CI, 0.66 to 1 1.1] per ITGB8 10 patient years and were independently associated with an IgG level 400mg/dL. Conclusion B cell targeted therapy causes a preferential decline in ANCA titers relative to total IgG levels. Despite prolonged maintenance therapy with rituximab, IgG levels remain essentially constant. Serious infections were rare. Introduction The anti-CD20 monoclonal antibody, rituximab, has emerged as a useful immunosuppressive agent for the treatment of several antibody-mediated autoimmune diseases (1, 2). An important immunosuppressive mechanism of rituximab is usually to attenuate the Givinostat hydrochloride production of pathogenic autoantibodies (3-5). The potential downside of this therapy is usually suppression of the protective benefits of the humoral immune system, thus predisposing to infectious complications (6, 7). The degree to which treatments using rituximab can suppress pathogenic autoantibodies, compared to suppression of protective antibodies, may be a major determinate of Givinostat hydrochloride the clinical value of these treatments. Characteristics of the disease, variations of the treatment regimen, and patient characteristics may heavily influence this balance. Rituximab has become an important component of the treatment of antineutrophil cytoplasmic antibody (ANCA) vasculitis (2, 8, 9). The Rituximab in ANCA-Associated Vasculitis (RAVE) trial suggested that an induction of remission regimen using rituximab with glucocorticoids was equivalent to one using cyclophosphamide with glucocorticoids (2). More recently, the Maintenance of Remission using Rituximab in Systemic ANCA-Associated Vasculitis (MAINRITSAN) trial suggested that rituximab with low-dose prednisone is usually superior to azathioprine with low-dose prednisone as maintenance therapy to prevent disease relapse (9). An additional randomized controlled trial evaluating rituximab for maintenance of remission is usually ongoing (10). Unfortunately, relapse is usually common in ANCA vasculitis following cessation of rituximab, and is often heralded by B cell reconstitution (11, 12). With the aim of preventing disease relapse, our practice has evolved to treat patients for extended periods of time with scheduled rituximab dosing to maintain B cell depletion (13). Data around the complications of such a treatment regimen, however, are sparse. One particular concern is the development of hypogammaglobulinemia and predisposition to serious infections. In this study, we retrospectively evaluate the impact of continuous B cell depletion with rituximab on immunoglobulin levels during induction and maintenance of remission therapy for ANCA vasculitis. In Givinostat hydrochloride particular, we compare the relative effect of treatment around the levels of pathogenic antibodies versus the effect on total immunoglobulin levels. In addition we describe serious adverse Givinostat hydrochloride events and identify predictive factors for the development of hypogammaglobulinemia and serious infections. Materials and Methods Study Population and Treatment Groups We performed a single-center retrospective analysis of 239 patients with ANCA vasculitis treated with rituximab-induced continuous B cell depletion at the Massachusetts General Hospital Vasculitis and Glomerulonephritis Center from April of 2006 to August of 2015. Patients were considered to have ANCA vasculitis if they had a positive test for antibodies to proteinase 3 (PR3) or myeloperoxidase (MPO) together with clinical and laboratory features consistent with granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), or one of the other related forms of vasculitis (14). Starting in 2006, our practice evolved into a consistent treatment regimen for induction and maintenance of remission in the majority of patients. For induction therapy, patients receive combination therapy with rituximab, a 2 month course of low-dose oral cyclophosphamide, and a short course of high dose steroids with a rapid taper to low dose. The rationale for combining rituximab with cyclophosphamide is usually to allow for rapid tapering of high-dose glucocorticoids, such that the prednisone dose is usually reduced to 15 mg daily by the fifth week.