Is Rituximab-Associated Hypogammaglobulinemia Always Linked to B-Cell Depletion?

We describe a case of a 3-year-old male toddler with a history of severe and refractory warm antibody autoimmune hemolytic anemia (w-AIHA) since early infancy and hypogammaglobulinemia persisting 20 months after rituximab administration (second-line rescue therapy). Specifically, although peripheral blood flow cytometry B-cell population counts signified B-cell recovery following completion of rituximab therapy, IgG levels were barely detectable. Detailed laboratory evaluation did not reveal any humoral or cell-mediated immunity impairment and the patient remained asymptomatic, without any infections or recurrence of w-AIHA. Due to severe hypogammaglobulinemia, he was placed on immunoglobulin replacement therapy (IVIG). The implemented PID (primary immunodeficiency) gene panel identified only variants of uncertain significance (VUS). The aim of this report is to underline the documentation of persisting hypogammaglobulinemia after rituximab despite peripheral blood B-cell reconstitution.