Increased Prevalence of Attention Deficit Hyperactivity Disorder in Individuals with Selective Immunoglobulin A Deficiency: A Nationwide Case-Control Study

Abstract

Background: Selective Immunoglobulin A Deficiency (SIgAD) is one of the most prevalent immunodeficiencies, characterized by an increased risk of mucosal infections. Attention deficit hyperactivity disorder (ADHD) is among the most common neurodevelopmental disorders and is associated with significantly higher rates of various infectious diseases, white blood cell abnormalities, and considerable morbidity. This study aimed to evaluate the prevalence of ADHD among patients with SIgAD. Methods: We conducted a retrospective, observational, population-based case-control study, within Leumit Health Services, by comparing individuals diagnosed with SIgAD to a matched control group. Data were extracted from electronic health records. Results: Of the >700,000 registered individuals, 772 aged ≥4 years with SIgAD were identified (mean age 22.0 ± 17.5 years; male/female ratio 1:1). The 5:1 matched control group consisted of 3860 subjects without SIgAD, with no significant differences between the groups regarding age, gender, ethnicity, and socioeconomic status. ADHD prevalence was significantly higher in the SIgAD group (16.2%) than in the control group (12.9%), with an odds ratio of 1.30 (95% confidence interval 1.05-1.61, p = 0.017), as was the use of methylphenidate (6.6% vs. 4%). Additionally, respiratory and intestinal infections were significantly more common in the SIgAD group (p < 0.001). Conclusion: A significantly higher prevalence of ADHD was observed in patients with SIgAD compared to strictly matched controls without SIgAD. These findings enhance our understanding of the pathophysiology of ADHD and its associated health complications.

Keywords: ADHD; immune deficiency; immunoglobulin A; infections; methylphenidate; neurodevelopmental disorders; secretory antibodies.