Autoantibodies involved in neuropsychiatric manifestations associated with systemic lupus erythematosus: a systematic review

Sciascia, Savino; Bertolaccini, Maria Laura; Roccatello, Dario; Khamashta, Munther A.; Sanna, Giovanni

doi:10.1007/s00415-014-7406-8

Cited by 91 publications

(82 citation statements)

References 59 publications

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“…The role played for other elements beyond autoantibodies in the NPSLE pathogenesis remains unclear. 29,30 This study analyses for the first time the serum complement components (C1q, C3 and C4), complement activation (CH50 and AP50), and anti-C1q and C1q CIC in a large and well-defined cohort of NPSLE with CNS involvement. The results in the present study have disclosed that none of the complement elements studied is useful to differentiate between NPSLE and SLE, but that some of them may be associated with a certain subset of NPSLE patients.…”

Section: Discussionmentioning

confidence: 99%

Complement levels and anti-C1q autoantibodies in patients with neuropsychiatric systemic lupus erythematosus

Magro-Checa

Schaarenburg

Beaart

et al. 2016

Lupus

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Objective: The objective of this paper is to analyse serum levels of anti-C1q, C1q circulating immune complexes (CIC), complement activation and complement components in systemic lupus erythematosus (SLE) patients during the first central nervous system neuropsychiatric (NP) event and to define the possible association between these results and clinical and laboratory characteristics. Methods: A total of 280 patients suspected of having NP involvement due to SLE were recruited in the Leiden NPSLE-clinic. All SLE patients were classified according to the ACR 1982 revised criteria for the classification of SLE. The clinical disease activity was measured by the SLE Disease Activity Index 2000 (SLEDAI-2K) and NP diagnoses were classified according to the 1999 ACR case definitions for NPSLE. We measured in serum of all patients anti-C1q and C1q CIC levels, the activation capacity of complement (CH50 and AP50) and different complement components (C1q, C3, C4). Results: In 92 patients the symptoms were attributed to SLE. NPSLE patients consisted of 63 patients with focal NPSLE and 34 patients with diffuse NPSLE. Anti-C1q antibodies were significantly higher and CH50, AP50 and C3 were significantly lower in NPSLE patients compared with SLE patients without NPSLE. This association was specially marked for diffuse NPSLE while no differences were found for focal NPSLE. After using potential predictors, decreased C4 remained significantly associated with focal NPSLE, but only when antiphospholipid antibodies (aPL) were included in the model. C3 and AP50 were independently associated with diffuse NPSLE. When SLEDAI-2K was included in the model these two associations were lost. When individual NPSLE syndromes were analysed, psychosis and cognitive dysfunction showed significantly lower values of complement activation capacity and all complement components. No significant associations were seen for other individual NPSLE syndromes. Conclusion: The associations between diffuse NPSLE and anti-C1q, C3/AP50 and focal NPSLE and C4 may be explained by disease activity and the presence of aPL, respectively. The role of complement activation and complement components in lupus psychosis and cognitive dysfunction merits further research. Lupus (2016) 25, 878-888.

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Section: Discussionmentioning

confidence: 99%

Complement levels and anti-C1q autoantibodies in patients with neuropsychiatric systemic lupus erythematosus

Magro-Checa

Schaarenburg

Beaart

et al. 2016

Lupus

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“…NPSLE may be the first manifestation of the disease and its prevalence ranges from 21% to 95% 5,6 . Central nervous system (CNS) syndromes are more common than peripheral and may be further classified into diffuse or focal manifestations 7 .…”

Section: Neuropsychiatric Systemic Lupus Erytematosusmentioning

confidence: 99%

“…Risk factors associated with NPSLE include CNS damage or generalized SLE activity; previous neuropsychiatric events or other concurring neuropsychiatric manifestations; the presence of moderate to high titers of antiphospholipid antibodies (aPL) such as lupus anticoagulant and anticardiolipin, or anti-β2 glycoprotein 1 (either IgG or IgM), especially in cerebrovascular disease, myelopathy, cognitive dysfunction, seizures and movement disorders; and anti-ribosomal P protein antibodies (anti-P antibodies), that have been associated with lupus psychosis in some studies 6,7,8,9 .…”

Section: Neuropsychiatric Systemic Lupus Erytematosusmentioning

confidence: 99%

“…Potential pathogenic mechanisms in primary NPSLE are direct action of intrathecal inflammatory cytokines, blood-brain barrier (BBB) disruption, accelerated atherosclerosis and thrombotic vasculopathy caused by aPL antibodies 4 . Autoantibodies may also bind to neurons leading to neuronal dysfunction and apoptosis 7,10 (Table 2).…”

Section: Neuropsychiatric Systemic Lupus Erytematosusmentioning

confidence: 99%

“…Anti-P antibodies have been specifically associated with psychosis in patients with SLE, although some studies have failed to verify this association 7,9 . High levels of anti-P antibodies found in serum samples of SLE patients with psychosis were compared to those of SLE patients with other neuropsychiatric manifestations, patients with non-SLE psychosis, and controls.…”

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confidence: 99%

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Neuropsychiatric Lupus in clinical practice

Alessi

Dutra

Neto

et al. 2016

Arq. Neuro-Psiquiatr.

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Systemic lupus erythematosus (SLE) is a chronic autoimmune disease involving multiple organs, characterized by the production of autoantibodies and the development of tissue injury. The etiology of SLE is partially known, involving multiple genetic and environmental factors. As many as 50% of patients with SLE have neurological involvement during the course of their disease. Neurological manifestations are associated with impaired quality of life, and high morbidity and mortality rates. Nineteen neuropsychiatric syndromes have been identified associated with SLE, and can be divided into central and peripheral manifestations. This article reviews major neuropsychiatric manifestations in patients with SLE and discusses their clinical features, radiological findings and treatment options.

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Anti–Ribosomal P Protein Autoantibodies From Patients With Neuropsychiatric Lupus Impair Memory in Mice

Bravo‐Zehnder

Toledo

Segovia-Miranda

et al. 2014

Arthritis & Rheumatology

100

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Objective. To define whether anti-ribosomal P (anti-P) autoantibodies from patients with neuropsychiatric systemic lupus erythematosus (NPSLE) impair the function of hippocampal neurons that express the neuronal surface P antigen (NSPA) when accessing the brain via circulating blood.Methods. We used anti-P antibodies from patients with NPSLE and rabbit-generated anti-P and anti-NSPA antibodies. Primary hippocampal neurons from mice were analyzed to determine antibody cell surface binding (double immunofluorescence), intracellular calcium variations (Fura 2 AM), and apoptosis (caspase 3 activation). Hippocampal-dependent spatial flexible memory was assessed in mice subjected to a water maze test 24 hours after an intravenous injection of anti-P or anti-NSPA, using lipopolysaccharide (LPS) to permeate the blood-brain barrier. Presence of antibodies and apoptosis in the hippocampus was studied using immunohistochemistry and TUNEL assays.Results. Hippocampal neurons expressed NSPA on the cell surface, as revealed by anti-P and anti-NSPA staining colocalization, and responded to both anti-P and anti-NSPA by exhibiting increased intracellular calcium levels. Neuronal apoptosis was induced when anti-P was directly injected by stereotaxis into the hippocampus or added to primary cultures. Upon LPS treatment, intravenously injected anti-P impaired memory but did not elicit neuronal apoptosis in the hippocampus, where it was detectable in low amounts. Anti-NSPA antibodies also impaired memory.Conclusion. Anti-P antibodies interact with NSPA on the surface of hippocampal neurons leading to apoptotic death or to functional perturbations, results that are likely dependent on the concentration of these antibodies. Circulating anti-P can access the hippocampus and impair memory without requiring neuronal death when the blood-brain barrier is disrupted. NSPA can mediate antibody-driven diffuse brain dysfunction, and anti-P might contribute to the cognitive impairment that is frequently observed in SLE.Controversy surrounds the clinical and pathogenic role of anti-ribosomal P (anti-P) protein autoantibodies in neuropsychiatric systemic lupus erythematosus (NPSLE) (1-4). Diffuse brain dysfunctions frequently occur in SLE without overt brain inflammation, and these dysfunctions thus might involve pathogenic autoantibodies, especially against neuronal surface components (5). An early study by Bonfa et al (6) revealed an association between blood circulating anti-P and lupus psychosis. Such an intriguing association has been confirmed by several studies and extended to other NPSLE manifestations but has not yet been extended to include cognitive impairment (1,2,7-10). Anti-P antibodies are also detected in the cerebrospinal fluid of patients with NPSLE, indicating blood-brain barrier permeation (9,11). However, conflicting clinical results and the as-yet little-understood mechanisms of neuropathogenesis mean that the role of anti-P is contentious (1-4).Experimental models and the identification of a neuronal surface target have pr...

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Autoantibodies involved in neuropsychiatric manifestations associated with systemic lupus erythematosus: a systematic review

Cited by 91 publications

References 59 publications

Complement levels and anti-C1q autoantibodies in patients with neuropsychiatric systemic lupus erythematosus

Complement levels and anti-C1q autoantibodies in patients with neuropsychiatric systemic lupus erythematosus

Neuropsychiatric Lupus in clinical practice

Anti–Ribosomal P Protein Autoantibodies From Patients With Neuropsychiatric Lupus Impair Memory in Mice

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