Abstract
BACKGROUND: Primary immunodeficiency (PI) is a group of heterogeneous disorders resulting from immune system defects. Over 70% of PI is undiagnosed, leading to increased mortality, co-morbidity and healthcare costs. Among PI disorders, combined immunodeficiencies (CID) are characterized by complex immune defects. Common variable immunodeficiency (CVID) is among the most common types of PI. In light of available treatments, it is critical to identify adult patients at risk for CID and CVID, before the development of serious morbidity and mortality. METHODS: We developed a deep learning-based method (named "TabMLPNet") to analyze clinical history from nationally representative medical claims from electronic health records (Optum® data, covering all US), evaluated in the setting of identifying CID/CVID in adults. Further, we revealed the most important CID/CVID-associated antecedent phenotype combinations. Four large cohorts were generated: a total of 47,660 PI cases and (1:1 matched) controls. RESULTS: The sensitivity/specificity of TabMLPNet modeling ranges from 0.82-0.88/0.82-0.85 across cohorts. Distinctive combinations of antecedent phenotypes associated with CID/CVID are identified, consisting of respiratory infections/conditions, genetic anomalies, cardiac defects, autoimmune diseases, blood disorders and malignancies, which can possibly be useful to systematize the identification of CID and CVID. CONCLUSIONS: We demonstrated an accurate method in terms of CID and CVID detection evaluated on large-scale medical claims data. Our predictive scheme can potentially lead to the development of new clinical insights and expanded guidelines for identification of adult patients at risk for CID and CVID as well as be used to improve patient outcomes on population level.