Interferon-λ-neutralizing autoantibodies and common autoimmune disease autoantibodies in pediatric acute-onset neuropsychiatric syndrome

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, urination, cognition, and behavior with increased emotional lability and irritability. Clinical observations, including physical exam and laboratory findings, show many similarities between PANS cases and pediatric autoimmune conditions. 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 225 plasma samples taken from 166 PANS patients during periods of active disease, or flares, in comparison with 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 scleroderma and GI/endocrine autoimmune conditions, reflective of clinical observations. Remarkably, a subset of PANS patients exhibits AAbs against interferon-λ, which is an important line of defense against infections at anatomic barriers. Furthermore, 9 of the 11 patients with IFN-λ-binding AAbs were found to be exhibit neutralizing activity. Overall, these findings demonstrate an autoimmune component to PANS and provide insight into a potential disease mechanism mediated by immune deficits at barrier surfaces.