Autoantibody profiling of autism spectrum disorder patients with monoamine oxidase a deficiency

Monoamine oxidase A (MAO A) is a key enzyme for serotonin metabolism. Knockout MAO A in mice results in elevated serotonin, altered serum autoantibodies, and autistic-like behavior. There is a subset of patients with autism spectrum disorder (ASD) who exhibit hyperserotonemia. The link between the MAO A, hyperserotonemia, immunity, and ASD is still unknown. To address this question, we harness the high-density human proteome microarray to profile the serum autoantibodies in ASD patients with or without MAO A deficiency. We recruited 25 subjects, including 20 ASD patients, from National Yang Ming Chiao Tung University Hospital and determined their plasma serotonin levels, screened for MAO A gene mutations and identified one patient with a C374 G mutation, which abolished MAO A activity and showed the highest serotonin level (hsASD; 518.42 ng/ml) and severe ASD symptoms. In another family with twin brothers, one was diagnosed with mild ASD and exhibited an increased serotonin level (isASD; 31.48 ng/ml), while the other twin was a healthy control. These three subjects were used for serum autoantibody profiling using high-density human proteome microarrays. Comparing serum antibodies from hsASD with healthy control, we identified 354 up-regulated and 398 down-regulated autoantibodies in hsASD. By comparing isASD with healthy controls, we reported 235 up-regulated and 279 down-regulated autoantibodies in isASD. Interestingly, the up-regulated autoantibodies for hsASD were enriched in the brain region and exhibited distinct features from that of isASD. This study indicates that MAO A deficiency and serotonin levels significantly impact the immunological changes in ASD patients, which may shed some light on pathological mechanisms and provide potential biomarkers for translational research in ASD.