Characterizing Autoimmune and End-Organ Lympho-Infiltrative Disease Burden in Childhood-Onset Common Variable Immunodeficiency

Background Common variable immunodeficiency (CVID) is the most prevalent inborn error of immunity. Although CVID is most commonly diagnosed in adulthood, a subset of patients is diagnosed in childhood. Autoimmune and end-organ lympho-infiltrative complications are common in adults with CVID and are associated with significant morbidity and mortality. Despite their clinical significance, the prevalence and timing of these complications in pediatric CVID remain poorly characterized. Methods We performed a retrospective analysis of clinical data from Beth Israel Lahey Health and Massachusetts General Hospital. We investigated the frequency, types, and natural history of autoimmune and inflammatory (AI) complications in patients diagnosed with CVID during childhood (<18 years old). Results We identified 36 patients (14 females, 22 males) diagnosed with CVID during childhood. The median age of diagnosis was 10 years old (interquartile range [IQR] 5–15). 56% (n = 19) of patients developed at least one AI complication during childhood. Cytopenias (anemia, neutropenia, lymphocytopenia, and thrombocytopenia) as well as gastrointestinal disease (enterocolitis, celiac disease, and other forms of malabsorption) were the most prevalent AI complications, each affecting 33% and 31% of patients, respectively. These complications typically appeared during childhood, often prior to CVID diagnosis. Interstitial lung disease, lymphadenopathy, splenomegaly, and liver disease were less common, each affecting <22% of patients; these complications tended to present later, into adulthood. Conclusion Our study demonstrated that AI complications—particularly cytopenias and gastrointestinal disease—occur frequently in patients diagnosed with CVID in childhood. Ongoing analyses will compare the prevalence, timing, and burden of these complications between pediatric- and adult-onset CVID and explore associated immunophenotypic differences. Our findings are limited by the small number of pediatric patients studied; larger studies are needed to better understand the natural history and risk factors for AI complications in childhood-onset CVID.