Anti-alpha-internexin autoantibody from neuropsychiatric lupus induce cognitive damage via inhibiting axonal elongation and promote neuron apoptosis
| Autor: | Yue-ying Gu, Chang-qing Zhu, Xiao-ye Lu, Li-Dong Huang, Xiao-Xiang Chen, Shuang Ye |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Pathology
medicine.medical_specialty Neurofilament Central nervous system Immunology/Autoimmunity lcsh:Medicine Apoptosis Enzyme-Linked Immunosorbent Assay Biology Mice Intermediate Filament Proteins medicine Animals Humans Lupus Erythematosus Systemic Fluorescent Antibody Technique Indirect Receptor lcsh:Science Autoantibodies Neurons Multidisciplinary Systemic lupus erythematosus Lupus erythematosus lcsh:R Autoantibody medicine.disease Axons Pathophysiology Mice Inbred C57BL medicine.anatomical_structure Neurological Disorders/Cognitive Neurology and Dementia Rheumatology/Systemic Lupus Erythematosos Immunology Female lcsh:Q Neuron Cognition Disorders Research Article |
| Zdroj: | PLoS ONE, Vol 5, Iss 6, p e11124 (2010) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | Background Neuropsychiatric systemic lupus erythematosus (NPSLE) is a major complication for lupus patients, which often leads to cognitive disturbances and memory loss and contributes to a significant patient morbidity and mortality. The presence of anti-neuronal autoantibodies (aAbs) has been identified; as examples, anti-NMDA receptors and anti-Ribsomal P aAbs have been linked to certain pathophysiological features of NPSLE. Methods and Findings In the current study, we used a proteomic approach to identify an intermediate neurofilament alpha-internexin (INA) as a pathogenetically relevant autoantigen in NPSLE. The significance of this finding was then validated in an expanded of a cohort of NPSLE patients (n = 67) and controls (n = 270) by demonstrating that high titers of anti-INA aAb was found in both the serum and cerebrospinal fluid (CSF) of ∼50% NPSLE. Subsequently, a murine model was developed by INA immunization that resulted in pronounced cognitive dysfunction that mimicked features of NPSLE. Histopathology in affected animals displayed cortical and hippocampal neuron apoptosis. In vitro studies further demonstrated that anti-INA Ab mediated neuronal damage via inhibiting axonal elongation and eventually driving the cells to apoptosis. Conclusions Taken together, this study identified a novel anti-neurofilament aAb in NPSLE, and established a hitherto undescribed mechanism of aAb-mediated neuron damage that could have relevance to the pathophysiology of NPSLE. |
| Databáze: | OpenAIRE |
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