Anti-alpha-internexin autoantibody from neuropsychiatric lupus induce cognitive damage via inhibiting axonal elongation and promote neuron apoptosis.
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.


RESULTS
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 approximately 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.
Lu
Xiao-ye
XY
Department of Rheumatology, Shanghai JiaoTong University School of Medicine, Shanghai, China.
Chen
Xiao-xiang
XX
Huang
Li-dong
LD
Zhu
Chang-qing
CQ
Gu
Yue-ying
YY
Ye
Shuang
S
D000818:Animals; D017209:Apoptosis; D001323:Autoantibodies / Q000276:immunology*; D001369:Axons; D003072:Cognition Disorders / Q000276:immunology* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007381:Intermediate Filament Proteins / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000473:pathology*
D001323:Autoantibodies; D007381:Intermediate Filament Proteins; C046643:alpha-internexin