Novel brain reactive autoantibodies: Prevalence in systemic lupus erythematosus and association with psychoses and seizures

Tin, Soe Kyaw; Xu, Qian; Thumboo, Julian; Lee, L.Y.; Tse, Chung Sang; Fong, Kok‐Yong

doi:10.1016/j.jneuroim.2005.07.015

Cited by 29 publications

(14 citation statements)

References 34 publications

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“…Mouse brain was utilized in order to avoid artifactual bands that result from the binding of secondary anti-human antibodies to endogenous immunoglobulins when using the sensitive chemiluminescence method of detection. Mouse tissue was specifically chosen among non-primate sources due to the high level of known homology and orthology between human and mouse proteomes (Southan, 2004), a strategy that has been used in other studies as well (Maruyama et al, 2004; Shoenfeld et al, 2003; Tin et al, 2005). Mouse (C57BL/6J strain) brain lysate was prepared as previously described (Alaedini et al, 2007).…”

Section: Methodsmentioning

confidence: 99%

Anti-neural antibody reactivity in patients with a history of Lyme borreliosis and persistent symptoms

Chandra

Wormser

Klempner

et al. 2010

Brain, Behavior, and Immunity

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Some Lyme disease patients report debilitating chronic symptoms of pain, fatigue, and cognitive deficits despite recommended courses of antibiotic treatment. The mechanisms responsible for these symptoms, collectively referred to as post-Lyme disease syndrome (PLS) or chronic Lyme disease, remain unclear. We investigated the presence of immune system abnormalities in PLS by assessing the levels of antibodies to neural proteins in patients and controls. Serum samples from PLS patients, post-Lyme disease healthy individuals, patients with systemic lupus erythematosus, and normal healthy individuals were analyzed for anti-neural antibodies by immunoblotting and immunohistochemistry. Anti-neural antibody reactivity was found to be significantly higher in the PLS group than in the post-Lyme healthy (p<0.01) and normal healthy (p<0.01) groups. The observed heightened antibody reactivity in PLS patients could not be attributed solely to the presence of cross-reactive anti-borrelia antibodies, as the borrelial seronegative patients also exhibited elevated anti-neural antibody levels. Immunohistochemical analysis of PLS serum antibody activity demonstrated binding to cells in the central and peripheral nervous systems. The results provide evidence for the existence of a differential immune system response in PLS, offering new clues about the etiopathogenesis of the disease that may prove useful in devising more effective treatment strategies.

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Section: Methodsmentioning

confidence: 99%

Anti-neural antibody reactivity in patients with a history of Lyme borreliosis and persistent symptoms

Chandra

Wormser

Klempner

et al. 2010

Brain, Behavior, and Immunity

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“…After a disruption of BBB, autoreactive Abs can penetrate into the brain where they may cause neuronal death [69] and eventually psychosis and/or seizures in lupus patients [119]. In addition to be detected in the CSF following BBB break, autoreactive Abs might also be produced intrathecally [40,120,121].…”

Section: Evidence Of Pathogenic Absmentioning

confidence: 99%

Neuropsychiatric systemic lupus erythematosus and cognitive dysfunction: The MRL-lpr mouse strain as a model

Jeltsch-David

Muller

2014

Autoimmunity Reviews

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Mouse models of autoimmunity, such as (NZB×NZW)F1, MRL/MpJ-Fas(lpr) (MRL-lpr) and BXSB mice, spontaneously develop systemic lupus erythematosus (SLE)-like syndromes with heterogeneity and complexity that characterize human SLE. Despite their inherent limitations, such models have highly contributed to our current understanding of the pathogenesis of SLE as they provide powerful tools to approach the human disease at the genetic, cellular, molecular and environmental levels. They also allow novel treatment strategies to be evaluated in a complex integrated system, a favorable context knowing that very few murine models that adequately mimic human autoimmune diseases exist. As we move forward with more efficient medications to treat lupus patients, certain forms of the disease that requires to be better understood at the mechanistic level emerge. This is the case of neuropsychiatric (NP) events that affect 50-60% at SLE onset or within the first year after SLE diagnosis. Intense research performed at deciphering NP features in lupus mouse models has been undertaken. It is central to develop the first lead molecules aimed at specifically treating NPSLE. Here we discuss how mouse models, and most particularly MRL-lpr female mice, can be used for studying the pathogenesis of NPSLE in an animal setting, what are the NP symptoms that develop, and how they compare with human SLE, and, with a critical view, what are the neurobehavioral tests that are pertinent for evaluating the degree of altered functions and the progresses resulting from potentially active therapeutics.

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“…Anti-ganglioside (anti-GM1) antibodies were once thought to be associated with NPSLE pathogenesis (4, 33) through disruption of voltage gated Na + channels found near nodes of Ranvier (34), though it has since been found that they are more likely associated with peripheral neuropathies than central NPSLE presentations (35). Other antibodies associated with NPSLE include anti-dsDNA, anti-Microtubule-associated Protein 2, anti-Triose-phosphate isomerase, and brain reactive autoantibodies (BRAA) (36–38). The reader is referred to a number of excellent reviews for further detail regarding these and other neuropathic antibodies (39–42).…”

Section: Neuropathic Antibodies In Npslementioning

confidence: 99%

Neuropsychiatric Lupus, the Blood Brain Barrier, and the TWEAK/Fn14 Pathway

2013

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Patients with systemic lupus erythematosus (SLE) can experience acute neurological events such as seizures, cerebrovascular accidents, and delirium, psychiatric conditions including depression, anxiety, and psychosis, as well as memory loss and general cognitive decline. Neuropsychiatric SLE (NPSLE) occurs in between 30 and 40% of SLE patients, can constitute the initial patient presentation, and may occur outside the greater context of an SLE flare. Current efforts to elucidate the mechanistic underpinnings of NPSLE are focused on several different and potentially complementary pathways, including thrombosis, brain autoreactive antibodies, and complement deposition. Furthermore, significant effort is dedicated to understanding the contribution of neuroinflammation induced by TNF, IL-1, IL-6, and IFN-γ. More recent studies have pointed to a possible role for the TNF family ligand TWEAK in the pathogenesis of neuropsychiatric disease in human lupus patients, and in a murine model of this disease. The blood brain barrier (BBB) consists of tight junctions between endothelial cells (ECs) and astrocytic projections which regulate paracellular and transcellular flow into the central nervous system (CNS), respectively. Given the privileged environment of the CNS, an important question is whether and how the integrity of the BBB is compromised in NPSLE, and its potential pathogenic role. Evidence of BBB violation in NPSLE includes changes in the albumin quotient (Qalb) between plasma and cerebrospinal fluid, activation of brain ECs, and magnetic resonance imaging. This review summarizes the evidence implicating BBB damage as an important component in NPSLE development, occurring via damage to barrier integrity by environmental triggers such as infection and stress; cerebrovascular ischemia as result of a generally prothrombotic state; and immune mediated EC activation, mediated by antibodies and/or inflammatory cytokines. Additionally, new evidence supporting the role of TWEAK/Fn14 signaling in compromising the integrity of the BBB in lupus will be presented.

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Novel brain reactive autoantibodies: Prevalence in systemic lupus erythematosus and association with psychoses and seizures

Cited by 29 publications

References 34 publications

Anti-neural antibody reactivity in patients with a history of Lyme borreliosis and persistent symptoms

Anti-neural antibody reactivity in patients with a history of Lyme borreliosis and persistent symptoms

Neuropsychiatric systemic lupus erythematosus and cognitive dysfunction: The MRL-lpr mouse strain as a model

Neuropsychiatric Lupus, the Blood Brain Barrier, and the TWEAK/Fn14 Pathway

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