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Serological comparison of systemic lupus erythematosus with neuropsychiatric lupus using synthetic nucleic acid antigens.

ABSTRACT: Neuropsychiatric systemic lupus erythematosus is an autoimmune disorder characterized by an irregular exchange between the central nervous system and the immune system, leading to the outbreak of neurological conditions with possible disabling effects. Although neuropsychiatric systemic lupus erythematosus is the most common expression of lupus condition, it is still poorly understood. In this study, we focus on the development of an advantageous method based on the application of synthetic nucleic acids and protein-based antigen arrays in order to characterize autoreactive antibodies in neuropsychiatric systemic lupus erythematosus. We confirmed the benefits of using synthetic oligonucleotides such as assay reproducibility, elevated affinity and specificity to autoreactive antibodies. We also demonstrated presence of autoantibodies towards three particular synthetic double stranded antigens and verify similarity of antinuclear antibody patterns in ordinary lupus and neuropsychiatric systemic lupus erythematosus.

SUBMITTER: Khatri S

PROVIDER: S-EPMC7652778 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Serological comparison of systemic lupus erythematosus with neuropsychiatric lupus using synthetic nucleic acid antigens.

Khatri Sangita S Psaraftis Nikos N Funaro Alessia A Arinuma Yoshiyuki Y Fujieda Yuichiro Y Mader Simone S Jørgensen Christian Damsgaard CD Astakhova Kira K

Journal of translational autoimmunity 20201028

Neuropsychiatric systemic lupus erythematosus is an autoimmune disorder characterized by an irregular exchange between the central nervous system and the immune system, leading to the outbreak of neurological conditions with possible disabling effects. Although neuropsychiatric systemic lupus erythematosus is the most common expression of lupus condition, it is still poorly understood. In this study, we focus on the development of an advantageous method based on the application of synthetic nucl ...[more]

PMID: 33205038

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Project description:Neuropsychiatric systemic lupus erythematosus (NPSLE) is a generic definition referring to a series of neurological and psychiatric symptoms directly related to systemic lupus erythematosus (SLE). NPSLE includes heterogeneous and rare neuropsychiatric (NP) manifestations involving both the central and peripheral nervous system. Due to the lack of a gold standard, the attribution of NP symptoms to SLE represents a clinical challenge that obligates the strict exclusion of any other potential cause. In the acute setting, management of these patients does not differ from other non-SLE subjects presenting with the same NP manifestation. Afterwards, an individualized therapeutic strategy, depending on the presenting manifestation and severity of symptoms, must be started. Clinical trials in NPSLE are scarce and most of the data are extracted from case series and case reports. High-dose glucocorticoids and intravenous cyclophosphamide remain the cornerstone for patients with severe symptoms that are thought to reflect inflammation or an underlying autoimmune process. Rituximab, intravenous immunoglobulins, or plasmapheresis may be used if response is not achieved. When patients present with mild to moderate NP manifestations, or when maintenance therapy is warranted, azathioprine and mycophenolate may be considered. When symptoms are thought to reflect a thrombotic underlying process, anticoagulation and antiplatelet agents are the mainstay of therapy, especially if antiphospholipid antibodies or antiphospholipid syndrome are present. Recent trials on SLE using new biologicals, based on newly understood SLE mechanisms, have shown promising results. Based on what we currently know about its pathogenesis, it is tempting to speculate how these new therapies may affect the management of NPSLE patients. This article provides a comprehensive and critical review of the literature on the epidemiology, pathophysiology, diagnosis, and management of NPSLE. We describe the most common pharmacological treatments used in NPSLE, based on both a literature search and our expert opinion. The extent to which new drugs in the advanced development of SLE, or the blockade of new targets, may impact future treatment of NPSLE will also be discussed.

Project description:About 40% of patients with systemic lupus erythematosus experience diffuse neuropsychiatric manifestations, including impaired cognition and depression. Although the pathogenesis of diffuse neuropsychiatric SLE (NPSLE) is not fully understood, loss of brain barrier integrity, autoreactive antibodies, and pro-inflammatory cytokines are major contributors to disease development. Fingolimod, a sphingosine-1-phosphate (S1P) receptor modulator, prevents lymphocyte egress from lymphoid organs through functional antagonism of S1P receptors. In addition to reducing the circulation of autoreactive lymphocytes, fingolimod has direct neuroprotective effects such as preserving brain barrier integrity and decreasing pro-inflammatory cytokine secretion by astrocytes and microglia. Given these effects, we hypothesized that fingolimod would attenuate neurobehavioral deficits in MRL-lpr/lpr (MRL/lpr) mice, a validated neuropsychiatric lupus model. Fingolimod treatment was initiated after the onset of disease, and mice were assessed for alterations in cognitive function and emotionality. We found that fingolimod significantly attenuated spatial memory deficits and depression-like behavior in MRL/lpr mice. Immunofluorescent staining demonstrated a dramatic lessening of brain T cell and macrophage infiltration, and a significant reduction in cortical leakage of serum albumin, in fingolimod treated mice. Astrocytes and endothelial cells from treated mice exhibited reduced expression of inflammatory genes, while microglia showed differential regulation of key immune pathways. Notably, cytokine levels within the cortex and hippocampus were not appreciably decreased with fingolimod despite the improved neurobehavioral profile. Furthermore, despite a reduction in splenomegaly, lymphadenopathy, and circulating autoantibody titers, IgG deposition within the brain was unaffected by treatment. These findings suggest that fingolimod mediates attenuation of NPSLE through a mechanism that is not dependent on reduction of autoantibodies or cytokines, and highlight modulation of the S1P signaling pathway as a novel therapeutic target in lupus involving the central nervous system.

Dataset Information

Serological comparison of systemic lupus erythematosus with neuropsychiatric lupus using synthetic nucleic acid antigens.

Publications

Serological comparison of systemic lupus erythematosus with neuropsychiatric lupus using synthetic nucleic acid antigens.

Similar Datasets

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