Unmasking Primary Immunodeficiency After Rituximab

Introduction Rituximab, an anti-CD40 antibody, is a commonly used B cell-depleting therapy. We present a case that illustrates the unveiling of an underlying common variable immune deficiency (CVID) after completion of rituximab therapy. Case Presentation An 18-year-old female with a history of myelin oligodendrocyte antibody disorder (MOGAD) treated with rituximab for 1.5 years was referred for recurrent infections, chronic cough, and intermittent fevers persisting for five months despite multiple antibiotic courses. She had completed her rituximab therapy six years ago. Flow cytometry during therapy had shown complete B cell depletion. At the clinic visit, laboratory results revealed severe hypogammaglobulinemia (IgG 166 mg/dL, IgM 19 mg/dL, and IgA <20 mg/dL) and absent diphtheria protection and a pneumococcal response to only 2/23 serotypes, with preserved tetanus titers. Genetic testing was also performed and revealed a heterozygous likely pathogenic TNFRSF13B variant associated with autosomal recessive CVID. The literature indicates that single pathogenic variants may contribute to CVID risk. In the setting of persistent hypogammaglobulinemia, impaired vaccine responses, recurrent infections, and genetic findings, she was diagnosed with CVID. Discussion While rituximab usually causes transient hypogammaglobulinemia, in patients with unrecognized inborn errors of immunity, hypogammaglobulinemia may be persistent and severe. Hypogammaglobulinemia after rituximab typically persists for six to 12 months. Prolonged hypogammaglobulinemia lasting longer than six to 12 months and poor vaccine responses after rituximab warrant immunologic evaluation. Additionally, baseline testing prior to initiating therapy may help distinguish secondary from primary immunodeficiency. Conclusion This case highlights the importance of differentiating primary immunodeficiencies from rituximab-induced hypogammaglobulinemia. Early recognition of underlying primary immunodeficiency would enable more timely management and ultimately reduce CVID-associated morbidity. Genetic testing plays a key role in confirming clinical suspicion.