Autoimmune Manifestations as Initial Presentation of NFKB-1 Mutation

NFKB1 plays a role in the regulation of the innate immune system, adaptive immune system, and inflammation through the canonical NFKB pathway, and therefore dysregulation in this pathway can lead to both immunodeficiency and immune dysregulation. Most commonly, NKFB1 deficiency is associated with both hypogammaglobulinemia and CVID-like phenotypes with loss-of-function mutations in NFKB1 reported to be the most common monogenetic cause of CVID. We present the case of a patient who presented with symptomatic immune-mediated thrombocytopenia and was subsequently found to have immunodeficiency in his labs, which led to the diagnosis of his NFKB1 deficiency, an inborn error of immunity. This case highlights that patients who present with severe and refractory autoimmune presentations may benefit from an immunology evaluation. A diagnosis of CVID not only places individuals at a higher risk of infection but also at an increased rate of lymphomas, gastrointestinal symptoms, granulomas, lymphadenopathy, and autoimmune phenomena. While previously primary immunodeficiency disorders were thought to present primarily with infections, we know now that noninfectious clinical manifestations can be the initial clinical presentation of an inborn error of immunity and these noninfectious manifestations increase associated morbidity and mortality. Therefore, it is crucial to recognize and evaluate these patients early to allow for appropriate treatment, counseling, and improved outcomes.