IgG Glycosylation Analysis in Patients with Ring14 Syndrome Unveils Novel Pathomechanisms and New Therapy Perspectives

Ring chromosome 14 (RC14) syndrome is an ultra-rare disorder characterized by drug-resistant epilepsy, intellectual disabilities, autism, and recurrent infections, sug-gesting a possible underlying immune dysregulation. We analyzed immunoglobulin G (IgG) N-glycosylation in six RC14 patients and compared it with age-matched healthy controls using ultra-high performance liquid chromatography (UHPLC) coupled with fluorescence detection (FLR) and high-resolution electrospray ionization mass spec-trometry (ESI-MS). Patients showed decreased galactosylation and sialylation, resembling pro-inflammatory patterns observed in autoimmune diseases. These alterations were not observed in total serum glycoproteins, indicating a selective effect on IgG. One patient treated with intravenous immunoglobulin (IVIG) showed clinical improvement, which led us to investigate around causality.