Anti-GAPDH autoantibodies as a pathogenic determinant and potential biomarker of neuropsychiatric diseases

OBJECTIVE: To investigate the potential role of circulating autoantibodies specific to neuronal cell surface antigens in the pathophysiology of neuropsychiatric disorders. METHODS: We performed two different kinds of immunoscreening approaches using sera from patients with schizophrenia to identify autoantigens associated with neuropsychiatric disorders. Then, we tested the presence of autoantibodies specific to the identified autoantigen in patients with various psychiatric disorders and systemic lupus erythematosus (SLE) with neuropsychiatric manifestations. Furthermore, we evaluated the potential pathogenic role of these autoantibodies both in vitro and in vivo. RESULTS: We identified glyceraldehyde 3-phosphate dehydrogenase (GAPDH) as a novel autoantigen associated with neuropsychiatric disorders. We detected serum anti-GAPDH IgG in 51% patients with schizophrenia and 50% patients with major depression. Moreover, patients suffering by SLE with comorbid psychiatric manifestations presented significantly higher serum level of anti-GAPDH antibodies than SLE patients without psychiatric manifestations (P= 0.004 by square Chi test). To note, a significant positive correlation (R = 0.48, P= 0.0049 by Spearman rank correlation test) was found between levels of serum anti-GAPDH antibodies and cognitive dysfunctions in patients with SLE. In vitro analysis of purified human anti-GAPDH autoantibodies effects on SH-SY5Y cells showed an immediate neurite retraction. Finally, in vivo administration of the anti-GAPDH autoantibodies in the right cerebral ventricle of C57BL6/J mice resulted in specific behavioral changes associated to a detrimental cognitive and emotional profile. CONCLUSION: Overall, these data suggest that anti-GAPDH autoantibodies play a role in the etiopathogenesis of neuropsychiatric disorders possibly representing a promising tool for the screening of individual vulnerability. This article is protected by copyright. All rights reserved.