Persistent Hypogammaglobulinemia Following Anti-CD20 Therapy in a Patient with 22q11.2 Deletion Syndrome: A Case Report
Ana Drazic, Srdjan Pasic, Maja Stojanovic, Branka Bonaci-Nikolic, Rada MiskovicIntroduction
22q11.2 deletion syndrome (22q11.2 DS) is one of the most common microdeletion syndromes, characterized by congenital anomalies and variable immune dysfunction secondary to thymic hypoplasia. The resulting immune dysregulation frequently predisposes affected individuals to autoimmune manifestations, including immune thrombocytopenia (ITP). Although rituximab is established therapy for refractory ITP, its B cell–depleting mechanism may carry distinct risk in patients whose B cell compartment already depends on impaired T cell–mediated help, potentially resulting in profound and irreversible humoral failure rather than the typically transient hypogammaglobulinemia.
Case Presentation
We report the case of a female patient whose initial clinical manifestations included characteristic facial dysmorphism, cleft palate, a hemodynamically significant ventricular septal defect requiring surgical correction at the age of three years, and delayed psychomotor development. Based on these findings, 22q11.2 DS was suspected and subsequently confirmed by fluorescence in situ hybridization (FISH) analysis at the age of nine. At the age of five, she developed severe ITP, refractory to glucocorticoids, intravenous immunoglobulins, and cyclosporine. Immunophenotyping of peripheral blood lymphocytes at this stage already revealed reduced B cell counts (8%, 0.105 × 109/L), while serum IgG levels remained within the normal range. At the age of 12, she received rituximab therapy, achieving a complete normalization of platelet counts. Within the following year, she developed recurrent bilateral pneumonias. Laboratory evaluation revealed severe hypogammaglobulinemia (IgG 0.6 g/L, IgM 0.04 g/L, and IgA 0.06 g/L), with a further reduction in B cell numbers (4%, 0.066 × 109/L). Monthly intravenous immunoglobulin replacement therapy, combined with antibiotic prophylaxis, significantly reduced the frequency of infections. Hypogammaglobulinemia and B cell deficiency persisted without recovery over more than a decade of follow-up. At the age of 24 years, the patient developed severe COVID-19 pneumonia, which ultimately resulted in a fatal outcome.
Conclusion
This case highlights that rituximab, while effective in the treatment of autoimmune cytopenias, may induce severe and persistent hypogammaglobulinemia in patients with underlying primary immunodeficiency and pre-existing B cell abnormalities. Our patient’s humoral failure after rituximab proved persistent, a finding that may be attributable to an underlying thymic-dependent defect in B cell maturation, which could impair normal post-depletion recovery. Comprehensive baseline immunological evaluation and long-term monitoring of immunoglobulin levels and B cell recovery should be considered before B cell–depleting therapies in this population.