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Research Article: Interferon-?-neutralizing autoantibodies and common autoimmune disease autoantibodies in pediatric acute-onset neuropsychiatric syndrome

Date Published: 2026-07-17

Abstract:
Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) is characterized by sudden onset obsessive-compulsive disorder (OCD) symptoms in conjunction with other neuropsychiatric manifestations including disturbances in sleep, cognition, and behavior. Studies have revealed high rates of autoimmune and inflammatory markers—as well as comorbid rheumatologic disease—in patients with PANS. While published studies have suggested autoantibodies are common in PANS patients, the molecular targets of these autoantibodies (AAbs) remain poorly characterized. Here, we profile the AAbs in 224 plasma samples taken from 166 PANS patients during periods of active disease, or flares, compared to 83 pediatric healthy controls using custom Luminex microbead panels conjugated with highly curated antigens from common autoimmune diseases as well as cytokines and chemokines. We find that PANS patients exhibit increased prevalence of AAbs against autoantigens known to be targeted in scleroderma and GI/endocrine autoimmune conditions. Furthermore, a subset of PANS patients exhibited AAbs against IFN-?, an important line of defense against infections at anatomic barriers. Among the 11 tested PANS plasma samples with IFN-?-binding AAbs, 9 showed detectable inhibition of IFN-? signaling, and 4 met our predefined stringent threshold for IFN-?-neutralizing activity, while no tested HC samples met this neutralization threshold. These findings support a link between autoimmunity and PANS, and may provide insight into a potential disease mechanism mediated by immune deficits at barrier surfaces in a subset of patients.

Introduction:
Obsessive-compulsive disorder (OCD) affects 1-4% of children worldwide and typically exhibits a gradual onset, often beginning in early or late adolescence. In a subset of cases, OCD symptoms appear abruptly and are thought to be triggered by infection, commonly Streptococcal infection ( 1 – 7 ). Detailed clinical studies have led to the designation by expert panel consensus of Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections (PANDAS) and the broader Pediatric Acute-onset…

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