The role of B cells and autoantibodies in neuropsychiatric lupus

Wen, Jing; Stock, Ariel; Chalmers, Samantha A.; Putterman, Chaim

doi:10.1016/j.autrev.2016.07.009

Cited by 36 publications

(17 citation statements)

References 70 publications

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“…Although the precise mechanism underlying each individual type of end-organ pathology in lupus has yet to be fully elucidated, autoantibody deposition is thought to be important in both types of tissue [ 5 , 21 ]. Other potential contributions of B cells to the mechanisms of target organ injury in lupus are antigen presentation and cytokine secretion [ 22 ]. Furthermore, we have previously shown that macrophages are important for the development of both spontaneous and ultraviolet B irradiation-induced skin lesions in lupus mice and in the pathogenesis of murine NPSLE [ 7 – 9 ].…”

Section: Discussionmentioning

confidence: 99%

Highly selective inhibition of Bruton’s tyrosine kinase attenuates skin and brain disease in murine lupus

et al. 2018

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BackgroundSystemic lupus erythematosus (SLE) is a systemic autoimmune disease that affects different end organs, including skin and brain. We and others have previously shown the importance of macrophages in the pathogenesis of cutaneous and neuropsychiatric lupus. Additionally, autoantibodies produced by autoreactive B cells are thought to play a role in both the skin and central nervous system pathologies associated with SLE.MethodsWe used a novel inhibitor of Bruton’s tyrosine kinase (BTK), BI-BTK-1, to target both macrophage and B cell function in the MRL-lpr/lpr murine model of SLE, and examined the effect of treatment on skin and brain disease.ResultsWe found that treatment with BI-BTK-1 significantly attenuated the lupus associated cutaneous and neuropsychiatric disease phenotypes in MRL/lpr mice. Specifically, BI-BTK-1 treated mice had fewer macroscopic and microscopic skin lesions, reduced cutaneous cellular infiltration, and diminished inflammatory cytokine expression compared to control mice. BTK inhibition also significantly improved cognitive function, and decreased accumulation of T cells, B cells, and macrophages within the central nervous system, specifically the choroid plexus.ConclusionsDirected therapies may improve the response rate in lupus-driven target organ involvement, and decrease the dangerous side effects associated with global immunosuppression. Overall, our results suggest that inhibition of BTK may be a promising therapeutic option for cutaneous and neuropsychiatric disease associated with SLE.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-017-1500-0) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Highly selective inhibition of Bruton’s tyrosine kinase attenuates skin and brain disease in murine lupus

et al. 2018

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“…During an inflammatory episode, perivascular accumulation of mononuclear cells and cytokines either in the systemic circulation or CNS may disrupt the blood brain barrier, allowing the passage of autoantibodies into the CNS [29,30]. Autoantibody deposition leads to neurotoxicity and glial cell activation, thereby producing an abundance of cytokines in the CNS and perturbing normal neuronal function.…”

Section: Proposed Mechanisms Of Npslementioning

confidence: 99%

Management of Psychosis in Neuropsychiatric Lupus

Kang

Mok

2019

Journal of Clinical Rheumatology and Immunology

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Manifestations of neuropsychiatric systemic lupus erythematosus (NPSLE) are heterogeneous. Acute psychosis is an uncommon but well-recognized manifestation of NPSLE. With no specific biomarkers to date, the diagnosis of NPSLE relies on clinical acumen for circumstantial evidence and exclusion of important differential diagnoses. The attribution of psychosis to NPSLE is facilitated by the application attribution models. In particular, the American College of Rheumatology nomenclature, Systemic Lupus International Collaborating Clinics attribution models and Italian algorithm for the attribution of psychosis to NPSLE are revisited. The mainstay of treatment for psychosis attributable to NPSLE is immunosuppression and symptomatic control. In refractory cases, immunomodulatory and emerging biological agents may be considered. This article reviews the diagnostic dilemma, pathogenic mechanisms and treatment of psychosis in SLE patients.

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“…A review article by Wen et al [ 21 ] states the role of B cells in the adverse behavioral symptoms in NPSLE as it crosses the blood-brain barrier and causes glial activation and neurodegeneration [ 21 ]. Improper regulation of cytokines IFN-α, tumor necrosis factor (TNF), and IL-6 may cause disruption of the BBB, and also the elevated levels of cytokines within the CNS such as TNF-like weak inducer of apoptosis (TWEAK) may be responsible for some of the neuropsychiatric changes in lupus [ 22 , 23 ].…”

Section: Reviewmentioning

confidence: 99%

Psycho-rheumatic Integration in Systemic Lupus Erythematosus: An Insight into Antibodies Causing Neuropsychiatric Changes

Nalakonda¹,

Islam²,

Chukwu³

et al. 2018

Cureus

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The main purpose of this paper is to bring together all the antibodies and markers related to neurological and psychiatric manifestations in systemic lupus erythematosus and also the pharmacology that could help treat these symptoms. Existing research data regarding specific antibodies involved in the disease process and drugs that were being studied was collected and analyzed. After reviewing the studies published by various authors, symptoms were shown to be mainly caused by antibodies against N-methyl-D-aspartate receptor (NMDAR) antibodies, anti-endothelial, anti-ribosomal P, antiphospholipid antibodies, cytokines like interferons and chemokines. The monoclonal antibody rituximab has shown to be beneficial in some of the cases. Based on all the articles reviewed, the antibodies and cytokines showed the most effective evidence in causing the different manifestations of neuropsychiatric systemic lupus erythematosus (NPSLE), but studies regarding the drugs being effective against all the symptoms are inconclusive as there are very few studies. Further research to support the drug’s effectiveness in managing the symptoms is needed. More studies are needed regarding early diagnosis of NPSLE using the antibodies as biomarkers as it could help in preventing these manifestations.

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The role of B cells and autoantibodies in neuropsychiatric lupus

Cited by 36 publications

References 70 publications

Highly selective inhibition of Bruton’s tyrosine kinase attenuates skin and brain disease in murine lupus

Highly selective inhibition of Bruton’s tyrosine kinase attenuates skin and brain disease in murine lupus

Management of Psychosis in Neuropsychiatric Lupus

Psycho-rheumatic Integration in Systemic Lupus Erythematosus: An Insight into Antibodies Causing Neuropsychiatric Changes

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