Can medication-induced B-cell depletion cause or unmask immunodeficiency?

Published Online: August 7, 2014

The use of immunomodulatory medications, such as rituximab, revolutionized the approach, treatment and prognosis of many diseases and has led to immeasurable improvement in patients’ quality of life. Rituximab depletes B-cells by targeting CD20 antigen on B-lymphocytes, which in turn, causes changes in immunologic interactions and blocks production of pathologic antibodies. While rituximab has transformed the way numerous autoimmune, hematologic and oncologic diseases are treated, there is inadequate data on the long-term effects of B-cell depletion.

In an article recently published in The Journal of Allergy and Clinical Immunology: In Practice, Kaplan and colleagues present a case series of patients who developed recurrent infections after treatment with rituximab. Post-treatment immune evaluation revealed that these patients had low immunoglobulin levels and impaired antibody production. Furthermore, B-cells production did not recover in 45% of these patients. The remaining patients regained normal or just-below-normal B-cell numbers, but with a significant delay. The average B-cell recovery time was 23 months versus the previously reported 6 to 9 months. These recovered B-cells were mostly naïve (immature) while switched memory (mature) B-cells were low, which is in agreement with previous reports.

Notably, B-cell phenotype of patients who developed infections after rituximab treatment was similar to B-cell phenotype of patients diagnosed with common variable immunodeficiency prior to rituximab treatment. All these patients were treated with immunoglobulin replacement therapy (IGRT) with no recurrence of severe infections afterwards. At the end of follow up period (range 1-6.5 years) 82% of patients were still requiring IGRT.

Although the majority of patients do not present with immunodeficiency after B-cell depletion therapy (BCDT), some develop clinically significant long-term B-cell dysfunction. These patients may have preexisting subclinical immune defect that is unmasked by the BCDT. Baseline immune evaluation with quantitative immunoglobulins and B-cell numbers prior to starting BCDT is paramount to differentiate between a preexisting primary immunodeficiency disease and a secondary rituximab-induced immune suppression. Periodic monitoring of B-cell numbers and serum immunoglobulins will help in following immune recovery and identifying patients at risk for significant infections after BCDT.

The authors propose the term “Persistent Immunodeficiency after Treatment with Immunomodulatory Drugs” (PITID) to characterize patients with medication-induced immunodeficiency. This diagnosis can be made with confidence only if clinicians perform a baseline immune evaluation before starting immunomodulators. Future prospective and controlled studies are necessary to identify the complete risks associated with the use of immunomodulatory drugs.

The Journal of Allergy and Clinical Immunology: In Practice is an official journal of the AAAAI, focusing on practical information for the practicing clinician.

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