LAUSR

Rituximab (RTX), a chimeric monoclonal antibody targeting CD20‐positive cells, is a valuable treatment option for malignant and benign immune‐related disorders. The rationale of targeting the CD20 antigen relies on depletion of both healthy and autoreactive/malignant CD20‐espressing cells, but normal B‐cell reconstitution is expected within months after treatment. Nevertheless, a number of recent studies have documented prolonged B‐cell deficiency associated with new‐onset hypogammaglobulinemia in patients receiving RTX. Awareness of post‐RTX hypogammaglobulinemia has become wider among clinicians, with a growing number of reports about the increased incidence, especially in children. Although these patients were previously regarded as affected by secondary/iatrogenic immunodeficiency, atypical clinical and immunological manifestations (e.g., severe or opportunistic infections; prolonged B‐cell aplasia) raise concerns of delayed manifestations of genetic immunological disorders that have been unveiled by B‐cell perturbation. As more patients with undiagnosed primary immune deficiency receiving RTX have been identified, it remains the challenge in discerning those that might display a higher risk of persistent RTX‐associated hypogammaglobulinemia and need a tailored immunology follow‐up. In this review, we summarize the principal evidence regarding post‐RTX hypogammaglobulinemia and provide a guideline for identifying patients at higher risk of RTX‐associated hypogammaglobulinemia that could harbor an inborn error of immunity.