Early-Onset Persistent Secondary Hypogammaglobulinaemia from In Utero Rituximab Exposure

We present a case of persistent hypogammaglobulinaemia secondary to antenatal rituximab exposure. The mother of our patient was treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) for non-Hodgkin lymphoma from 17 to 34 weeks of pregnancy. The patient presented with recurrent infections, including cervical lymphadenitis (16 months), two right upper lobe pneumonias (28 and 31 months), multiple episodes of otitis media, frequent wet coughs, and growth below 3rd centile. At 31 months, he was found to have profound hypogammaglobulinaemia (IgG < 0.3 g/L, IgA < 0.05 g/L, and IgM 1.6 g/L). Lymphocyte subsets were within normal range; however, switched memory B cells were low. A primary immune deficiency gene panel was negative (Blueprint Genetics 14/01/2022–Primary Immunodeficiency Panel Plus). The patient commenced immunoglobulin replacement and had marked reduction in acute infections, with no further invasive bacterial infections. At 5.5 years, his IgA and switched memory B cells are undetectable. This suggests a persistent effect on B cell class switching despite B cell compartment reconstitution. Rituximab causes transient depletion of CD20-expressing B cells and is placentally transferred by the FcRn receptor, detectable for months after delivery. Early-life exposure to rituximab may profoundly affect infant B cell compartment development, likely dependent on dose and timing. There are limited descriptions of immunological outcomes following in utero rituximab exposure; however, case series report transient B cell lymphopenia in some infants, which resolves within six months [1-3]. In a recent case series, four of eleven patients antenatally exposed to R-CHOP required immunoglobulin replacement, one of whom had persistent hypogammaglobulinaemia at four years of age [1]. Our case describes early-onset persistent secondary hypogammaglobulinaemia from in utero rituximab exposure and highlights the importance of immune monitoring following maternal immunosuppression during pregnancy.