Prolonged Neonatal Hypogammaglobulinemia Secondary to Maternal B Cell–Depleting Therapy

Rituximab is an anti-CD20 monoclonal antibody commonly used as a disease-modifying antirheumatic drug for multiple autoimmune conditions. Rituximab crosses the placenta and has been associated with transient B cell lymphopenia, hypogammaglobulinemia, and decreased response to vaccines in infants exposed in utero. While transient effects of rituximab have been reported in infancy, most affected infants are asymptomatic, and there are no reports on its effects beyond the first year of life. We present the case of an infant with in utero rituximab exposure, who developed persistent secondary hypogammaglobulinemia and recurrent sinopulmonary infections, necessitating immunoglobulin replacement (IVIG) therapy. Case The patient was a full-term male infant born to a mother with mixed connective tissue disease and systemic lupus erythematosus. The patient’s mother received rituximab, azathioprine, and hydroxychloroquine during pregnancy. The patient initially presented at 5 weeks of age for evaluation of absent T cell receptor excision circles on newborn screening. Immunophenotyping demonstrated mild T cell lymphopenia, absent B cells, and low IgA and IgM at 2 mg/dl and <4 mg/dl, respectively. IgG was normal (332 mg/dl). He had normal naive and memory T cell proportions and proliferations to mitogens. By 6 months of age, the patient had developed recurrent sinopulmonary infections. While T and B cell numbers were normal, switched memory B cells were entirely absent, and unswitched memory B cell percentages were low. IgG, IgA, and IgM were low at <40 mg/dl, <4 mg/dl, and 3 mg/dl, respectively, and pneumococcal and tetanus IgG levels were non-protective despite complete primary immunization series. IVIG was initiated, and the patient has remained stable on monthly IVIG therapy. Re-evaluation at 16 months demonstrated ongoing low IgM, IgA, and a persistently low percentage of switched memory B cells. Conclusion A full-term infant with in utero rituximab exposure had persistent secondary immune deficiency with prolonged suppression of production of immunoglobulins and switched memory B cells. Contrary to prior reports, maternal rituximab therapy may have resulted in prolonged effects on the developing neonatal immune system beyond the first year of life. This highlights the importance of ongoing monitoring of immune status, including B cell phenotyping in patients with in utero rituximab exposure.