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

SUMMARY

This study examined the prevalence and potential significance of autoantibodies in children with Pediatric Acute-onset Neuropsychiatric Syndrome (PANS), focusing on antibodies associated with established autoimmune diseases and antibodies that target interferon lambda (IFN-λ), an important component of the body’s antiviral immune defense. Researchers used plasma samples stored in the Stanford Biobank and collected during disease flares from 166 children with PANS and compared them with healthy pediatric controls. The investigators employed multiplex autoantibody profiling to evaluate a broad range of immune targets. They found that children with PANS were more likely to harbor autoantibodies commonly associated with connective tissue, gastrointestinal, and endocrine autoimmune diseases, particularly those linked to scleroderma-related and GI/endocrine conditions. These findings complement prior clinical observations that many patients with PANS exhibit clinical and laboratory features suggestive of immune dysregulation, including arthritis, enthesitis, elevated immune complexes, low complement C4 levels, and redness and swelling surrounding the nail folds.

The investigators also identified a subset of patients with antibodies directed against IFN-λ, a cytokine that plays a critical role in protecting mucosal surfaces from viral infections. Functional testing demonstrated that many of these antibodies were capable of reducing IFN-λ signaling, suggesting they were not merely present but biologically active. Although these neutralizing antibodies were found in only a small subset of patients and were not clearly associated with disease activity over time, their presence raises the possibility that impaired antiviral immune responses at barrier tissues could contribute to disease susceptibility or persistence in some individuals. The authors emphasize that these findings should not yet be considered diagnostic biomarkers but instead represent an important avenue for future investigation into immune mechanisms underlying PANS. Overall, the study strengthens evidence supporting immune dysregulation and autoimmunity as components of PANS while identifying IFN-λ-neutralizing autoantibodies as a novel and potentially important area for future mechanistic and translational research.

LINK TO PAPER: https://doi.org/10.3389/fimmu.2026.1832833