Immunity and Acquired Alterations in Cognition and Emotion: Lessons from SLE

Diamond, Betty; Kowal, Czeslawa; Huerta, Patricio T.; Aranow, Cynthia; Mackay, Meggan; DeGiorgio, Lorraine A.; Lee, Ji; Triantafyllopoulou, Antigone; Cohen-Solal, Joël; Volpe, Bruce T.

doi:10.1016/s0065-2776(05)89007-8

Cited by 38 publications

(33 citation statements)

References 161 publications

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“…AutoAbs and cytokines found in the serum and cerebrospinal fluid (CSF) of patients have been proposed as important factors in the etiology of CNS damage [31][32][33][34][35][36]. Furthermore, a disruption of the BBB's integrity, allowing diffusion of proteins and small molecules such as Table 1 Neuropsychiatric syndromes associated with SLE 1 , as defined by ACR nomenclature [9].…”

Section: Npsle: Cns Involvement In Human Slementioning

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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Section: Npsle: Cns Involvement In Human Slementioning

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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“…These agents might directly cause injury, or recruit CNS-resident cells to mediate an inflammatory process. While some neurotoxic antibodies have been identified, [3][4][5] it is likely that many more-as yet unidentified-antibodies affect neuronal viability, function, or both, either directly or through their effects on astrocytes and glial cells. CNS symptoms are likely to arise independently of systemic disease activity; the insults that breach the blood-brain barrier might result from infection, hypertension or behaviors such as smoking, and could lead to surges of antibody penetration of the CNS or to chronic small leaks in barrier protection.…”

mentioning

confidence: 99%

“…Alternatively, although the acetylcholine receptor is the only specific antigen that has been identified as a target in the PNS manifestations of NPSLE, it is highly likely that many antigens exist and that they will differ from antigenic targets in CNS disease. For example, anti-N-methyl D-aspartate receptor antibodies can bind to CNS neurons and affect viability and function, 5 but there is little evidence that N-methyl D-aspartate receptors are expressed on peripheral neurons. Antibodies to peripheral nerves have no anatomic barrier to impede interaction with the target antigen; therefore, there should be a direct relationship between the serum antibody titer and clinical symptoms.…”

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confidence: 99%

Neuropsychiatric systemic lupus erythematosus reconsidered

et al. 2008

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With the improved longevity of patients, it is increasingly appreciated that neuropsychiatric systemic lupus erythematosus (NPSLE) is a major cause of chronic disability, and that there are few specific therapies for many of the disease manifestations. In the 1999 consensus conference, the most recent of several consensus conferences on NPSLE, 19 specific syndromes affecting the neuromuscular junction, nerves, nerve roots, spinal cord, meninges or brain were designated to be potentially disease-related. 1 This categorization considers stroke, seizure, movement disorders, transverse myelitis, insidiously progressive cognitive impairments, thought and mood disorders, headaches and neuropathy as a single disease entity, implying that there might be shared pathoetiologic features among these symptoms. Although the 1999 guidelines have been useful in the clinical setting, they have been less useful for dissecting pathological mechanisms of NPSLE or identifying appropriate thera pies. Some impediments to the progression of our understanding of NPSLE seem to relate to the current classification of symptoms; therefore, it is timely to consider a reclassification of symptoms based on a pathoanatomic localization of the disease: vascular, central nervous system (CNS) and peripheral nervous system (PNS).Vascular disease begins within vessels and does not involve a neuron-specific mechanism; injury depends on the location, duration and degree of vascular compromise. Vascular compromise of the brain or spinal cord from an embolus or thrombosis has been associated with antibodies that bind cardiolipin, phospholipids and other (as yet unidentified) molecules, activate a clotting cascade, and promote a hyper-coagulable state. 2 There is also evidence that these antibodies directly or indirectly activate endothelial cells. The etiology and treatment of thrombosis in the brain vasculature in NPSLE does not differ significantly from the etiology and treatment of thrombosis occurring elsewhere in patients with SLE. Although increases in intracranial pressure can be responsible, headaches in NPSLE are most often a result of vascular pathology: changes in vascular tone that result in headache are likely to relate to effects on endothelial and smooth muscle cells that are mediated by antibodies, cytokines or vasoactive molecules. A therapeutic approach to vascular NPSLE manifestations could involve deletion or inactivation of autoantibodies, interference with the clotting cascade, or inhibition of endothelial cell activation. Although rare, it should be noted that inflammation of small-tomedium-sized blood vessels in the CNS or PNS can also cause vascular disruption.

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“…Se encuentran de 5% a 13% de los pacientes con LES. Son específicos de LES, y se han relacionado con LESNP en globo (psicosis lúpica y trastornos depresivos), pero con una potencia predictora dé-bil 21,34,[44][45][46][47][48] . Recientemente, Matus et al, trabajando en nuestro laboratorio, identificaron un autoanticuerpo proveniente de una paciente con psicosis lúpica dirigido contra un antígeno P ubicado en la superficie neuronal (llamado NSPA por sus siglas en inglés), reconocido por autoanticuerpos anti-P 49 .…”

Section: Autoanticuerpos En Lesnpunclassified