Pathogenesis of neuropsychiatric systemic lupus erythematosus and potential biomarkers

Abstract

Systemic lupus erythematosus is a chronic, multisystemic, autoimmune disease that may involve the central, peripheral, and autonomic nervous systems and can present with a wide variety of neurological and psychiatric manifestations. In this article, we review the recent literature pertaining to the pathogenesis of neuropsychiatric systemic lupus erythematosus (NPSLE). We searched the PUBMED database with no chronological constraints using the following terms: "neuropsychiatric systemic lupus erythematosus" cross-referenced with the terms "pathogenesis" and "biomarkers" for full-text articles in English. The etiology of NPSLE is as yet unknown, though numerous autoantibodies and cytokines have been suggested as possible mediators. Of the numerous autoantibodies and biomarkers examined, anti-phospholipid, anti-ribosomal P, anti-neuronal, anti-glial fibrillary acidic protein (GFAP), anti-endothelial cell, anti-N-methyl-D: -aspartate (NMDA), microtubule-associated protein 2 (MAP-2), and matrix metalloproteinase-9 (MMP-9) appear to be elevated in patients with NPSLE. Cytokines that may be involved in the pathology of NPSLE include interleukin (IL)-2, IL-6, IL-8, IL-10, tumor necrosis factor (TNF)-alpha, and interferons (IFN)-alpha and -gamma. With continued advances in immunological research, new insights into the pathophysiologic mechanisms of NPSLE may lead to the development of biomarkers and new treatment strategies.

Neuropsychiatric manifestations and associated autoantibodies in systemic lupus erythematosus patients from Western India

“…Anti-Rib-P antibodies were thought to be one of the biomarkers for NPSLE [12][13][14][15][16][17][18]. Anti-Rib-P antibodies and their associations with neuropsychiatric manifestations were also reported by Hassan et al [15] among Pakistani SLE patients.…”

“…The same can be said about anti-neuronal nuclear antibodies (ANNA). How et al [17][18][19][20] had reported that ANNA antibodies were strongly associated with NP manifestations in SLE. In our study, the incidence of true anti-neuronal antibodies after absorption of ANNA showed no statistically significant difference the incidence of Rib-P antibodies between NPSLE and SLE patients without neuropsychiatric involvement.…”

Parkinsonism as a Manifestation of Neuropsychiatric Systemic Lupus Erythematosus: A Case Report and Literature Review

“…[3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] Autoantibodies and immune-mediated vasculopathy was suggested in the pathogenesis of parkinsonism in NPSLE. 20 Kunas et al 4 found antibodies to dopaminergic cells in serum from the NPSLE patients manifested with parkinsonism. They concluded that antidopamine antibodies could be specific to NPSLE patients with parkinsonism.…”

Successful Treatment of Lupus Cerebrovascular Disease with Mycophenolate Mofetil

“…In addition, autoantibodies against the nerve cell body, axon, endothelial cells and histone, for example, are frequently recognized in NPSLE patients (11,12). One of the pathogenic mechanisms is thought to be that these antibodies induce apoptosis and alter expression level of adhesion molecules of endothelial cells in the blood-brainbarrier, allowing the passage of toxic components and antineuronal antibodies into the central nervous system (12).…”