New insights into the pathogenesis of systemic lupus erythematosus

Kyttaris, Vasileios C.; Katsiari, Christina G.; Juang, Yuang-Taung; Tsokos, George C.

doi:10.1007/s11926-005-0054-3

Cited by 25 publications

(13 citation statements)

References 60 publications

(60 reference statements)

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“…This may ultimately contribute to the neurodegeneration and neurological dysfunction seen in NP lupus ( Fig. 1) (Svenungsson et al, 2001;Jongen et al, 1990;Hafler and Weiner, 1989;Brey et al, 1997a;Shanks et al, 1999;Sakic et al, 1999;Ballok et al, 2003;Kyttaris et al, 2005). The precise regulatory mechanisms of cytokines in this dynamic autoimmune disease, however, remain unresolved.…”

Section: Prelude To Cns Damage: Disruption Of the Blood-brain Barriermentioning

confidence: 99%

Neuroimmunopathology in a murine model of neuropsychiatric lupus

Ballok

2007

Brain Research Reviews

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Animal models are extremely useful tools in defining pathogenesis and treatment of human disease. For many years researchers believed that structural damage to the brain of neuropsychiatric (NP) patients lead to abnormal mental function, but this possibility was not extensively explored until recently. Imaging studies of NP-systemic lupus erythematosus (SLE) support the notion that brain cell death accounts for the emergence of neurologic and psychiatric symptoms, and evidence suggests that it is an autoimmunity-induced brain disorder characterized by profound metabolic alterations and progressive neuronal loss. While there are a number of murine models of SLE, this article reviews recent literature on the immunological connections to neurodegeneration and behavioral dysfunction in the Fas-deficient MRL model of NP-SLE. Probable links between spontaneous peripheral immune activation, the subsequent central autoimmune/inflammatory responses in MRL/MpJ-Tnfrsf6 lpr (MRL-lpr) mice and the sequential mode of events leading to Fas-independent neurodegenerative autoimmune-induced encephalitis will be reviewed. The role of hormones, alternative mechanisms of cell death, the impact of central dopaminergic degeneration on behavior, and germinal layer lesions on developmental/regenerative capacity of MRL-lpr brains will also be explored. This model can provide direction for future therapeutic interventions in patients with this complex neuroimmunological syndrome.

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Section: Prelude To Cns Damage: Disruption Of the Blood-brain Barriermentioning

confidence: 99%

Neuroimmunopathology in a murine model of neuropsychiatric lupus

Ballok

2007

Brain Research Reviews

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“…Systemic lupus erythematosus (SLE) is a chronic and systemic autoimmune disease that is characterized by autoantibody production, abnormalities of immune-inflammatory system function, and inflammatory manifestation in several organs [1]. Genetic factors play an important role in the susceptibility to its development.…”

Section: Introductionmentioning

confidence: 99%

MCP-1, RANTES, and SDF-1 polymorphisms in Mexican patients with systemic lupus erythematosus

et al. 2007

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“…Each of these immune cell subpopulations display aberrant activation and function in SLE that is likely to contribute to disease pathogenesis (14). Monocytes/macrophages (Mo/Mϕ) have been increasingly recognized to play a dynamic role in the initiation and perpetuation of SLE given their hallmark functions in phagocytosis and antigen presentation (15, 16).…”

mentioning

confidence: 99%

Interferon regulatory factor 5 activation in monocytes of systemic lupus erythematosus patients is triggered by circulating autoantigens independent of type I interferons

Stone

Feng

Deng

et al. 2012

Arthritis & Rheumatism

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Objective Genetic variants of interferon regulatory factor 5 (IRF5) are associated with susceptibility to systemic lupus erythematosus (SLE). IRF5 regulates the expression of proinflammatory cytokines and type I interferons (IFN) believed to be involved in SLE pathogenesis. The aim of this study was to determine the activation status of IRF5 by assessing its nuclear localization in immune cells of SLE patients and healthy donors, and to identify SLE triggers of IRF5 activation. Methods IRF5 nuclear localization in subpopulations of peripheral blood mononuclear cells (PBMC) from 14 genotyped SLE patients and 11 healthy controls was assessed using imaging flow cytometry. IRF5 activation and function were examined after ex vivo stimulation of healthy donor monocytes with SLE serum or components of SLE serum. Cellular localization was determined by ImageStream and cytokine expression by Q-PCR and ELISA. Results IRF5 was activated in a cell type-specific manner; monocytes of SLE patients had constitutively elevated levels of nuclear IRF5 compared to NK and T cells. SLE serum was identified as a trigger for IRF5 nuclear accumulation; however, neither IFNα nor SLE immune complexes could induce nuclear localization. Instead, autoantigens comprised of apoptotic/necrotic material triggered IRF5 nuclear accumulation in monocytes. Production of cytokines IFNα, TNFα and IL6 in monocytes stimulated with SLE serum or autoantigens was distinct yet correlated with the kinetics of IRF5 nuclear localization. Conclusion This study provides the first formal proof that IRF5 activation is altered in monocytes of SLE patients that is in part contributed by the SLE blood environment.

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New insights into the pathogenesis of systemic lupus erythematosus

Cited by 25 publications

References 60 publications

Neuroimmunopathology in a murine model of neuropsychiatric lupus

Neuroimmunopathology in a murine model of neuropsychiatric lupus

MCP-1, RANTES, and SDF-1 polymorphisms in Mexican patients with systemic lupus erythematosus

Interferon regulatory factor 5 activation in monocytes of systemic lupus erythematosus patients is triggered by circulating autoantigens independent of type I interferons

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