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

Arthritis Rheum. 2010 Jun;62(6):1755-62. doi: 10.1002/art.27435.


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.

Publication types

  • Case Reports

MeSH terms

  • Aged
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Murine-Derived
  • Antirheumatic Agents / therapeutic use
  • Autoantibodies / blood
  • Autoantibodies / immunology
  • Autoimmune Diseases / blood
  • Autoimmune Diseases / diagnosis
  • Autoimmune Diseases / immunology
  • Autoimmune Diseases / therapy*
  • Combined Modality Therapy
  • Drug Administration Schedule
  • Female
  • Glucocorticoids / therapeutic use
  • Humans
  • Immunoglobulin G / blood*
  • Immunoglobulin G / immunology
  • Male
  • Methylprednisolone / therapeutic use
  • Middle Aged
  • Rituximab
  • Scleroderma, Systemic / blood
  • Scleroderma, Systemic / diagnosis
  • Scleroderma, Systemic / immunology
  • Scleroderma, Systemic / therapy*
  • Severity of Illness Index
  • Treatment Outcome


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Murine-Derived
  • Antirheumatic Agents
  • Autoantibodies
  • Glucocorticoids
  • Immunoglobulin G
  • Rituximab
  • Methylprednisolone