W139 - Recurrent Immune Thrombocytopenia Unmasking an Atypical CVID Phenotype

Abstract Text: Common Variable Immunodeficiency (CVID) is a primary immunodeficiency characterized by impaired B-cell differentiation and defective antibody production, typically resulting in recurrent infections, autoimmune manifestations, and increased malignancy risk. However, significant clinical heterogeneity exists, and autoimmune cytopenias may be the predominant or initial presentation.

We present the case of a Caucasian female diagnosed with immune thrombocytopenia (ITP) at age 18, achieving remission with corticosteroids. Her history included cold-induced urticaria, pernicious anemia, and iron deficiency anemia, but no significant infections. At age 21, she experienced an ITP relapse with severe thrombocytopenia (nadir: 2 × 10⁹/L). Immunologic workup revealed selective IgA deficiency with normal IgG and IgM levels but impaired vaccine-specific responses. Flow cytometry showed preserved T-cell counts but abnormal B-cell maturation, including decreased class-switched memory B cells (CD19+CD27+IgD-, 6%), reduced unswitched memory B cells (CD19+CD27+IgD+, 1%), and elevated naïve B cells (CD19+CD27-IgD+, 83%). Genetic testing identified variants of uncertain significance (VUS) in FOXI3 and SAMD9, genes involved in immune and hematopoietic regulation, potentially contributing to the underlying immune dysregulation. Treatment with corticosteroids and IVIG led to sustained ITP remission.

This case highlights the clinical diversity of CVID and supports the recognition of ITP as a potential dominant or sole manifestation. Recurrent autoimmune cytopenias, even in the absence of marked hypogammaglobulinemia or infections, should prompt evaluation for CVID. Early immunophenotyping and genetic analyses can clarify the diagnosis, enhance therapeutic planning, and improve clinical outcomes.