Rituximab therapy leads to rapid decline of serum IgG4 levels and prompt clinical improvement in IgG4‐related systemic disease

Abstract

Objective Patients with IgG4‐related systemic disease (IgG4‐RSD) frequently show an incomplete response to treatment with glucocorticoids and traditional disease‐modifying antirheumatic drugs (DMARDs). B lymphocyte depletion is a therapeutic strategy known to be effective for pemphigus vulgaris, an autoimmune condition mediated by IgG4 autoantibodies. This study was performed to assess the clinical and serologic responses to B lymphocyte depletion therapy with rituximab in patients with IgG4‐RSD. Methods Four patients with IgG4‐RSD were treated with 2 intravenous doses (1 gram each) of rituximab. Clinical improvement was assessed by monitoring the tapering/discontinuation of prednisone and DMARDs, and by measuring the serum concentrations of B lymphocytes, immunoglobulins, and IgG subclasses before and after therapy. Results Clinical features of IgG4‐RSD in these 4 patients included autoimmune pancreatitis, sclerosing cholangitis, lymphoplasmacytic aortitis, salivary gland involvement, orbital pseudotumor, and lacrimal gland enlargement. The 3 patients with elevated serum IgG and IgG4 levels at baseline had a mean IgG concentration of 2,003 mg/dl (normal range 600–1,500 mg/dl) and a mean IgG4 concentration of 2,160 mg/dl (normal range 8–140 mg/dl). Among these patients, the serum IgG4 concentrations declined by a mean of 65% within 2 months of rituximab administration. All 4 patients demonstrated striking clinical improvement within 1 month of the initiation of rituximab therapy, and tapering or discontinuation of their treatment with prednisone and DMARDs was achieved in all 4 patients. A decrease in IgG concentration was observed for the IgG4 subclass only. Conclusion Treatment with rituximab led to prompt clinical and serologic improvement in these patients with refractory IgG4‐RSD, and is a viable treatment option for this condition. The decline in serum IgG4 concentrations was substantially steeper than that of the autoantibody concentrations in immune‐mediated conditions in which rituximab is effective, such as in rheumatoid arthritis. In addition, the reduction in IgG‐subclass levels appeared to be specific for IgG4. The swift improvement of IgG4‐RSD suggests that rituximab achieves its effects in IgG4‐RSD by depleting the pool of B lymphocytes that replenish short‐lived IgG4‐secreting plasma cells.