Distinguishing the cerebrospinal fluid cytokine profile in neuropsychiatric systemic lupus erythematosus from other autoimmune neurological diseases

Ichinose, Kunihiro; Arima, Kei; Ushigusa, Takeshi; Nishino, Ayako; Nakashima, Yoshikazu; Suzuki, Takahisa; Horai, Yoshiro; Nakajima, Hideki; Kawashiri, Shin‐ya; Iwamoto, Naoki; Tamai, Mami; Nakamura, Hideki; Origuchi, Tomoki; Motomura, Masakatsu; Kawakami, Atsushi

doi:10.1016/j.clim.2015.01.010

Cited by 39 publications

(15 citation statements)

References 40 publications

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“…8 Interestingly, SLE patients who developed neuropsychiatric symptoms also had higher levels of pro-inflammatory cytokines in their CSF. 4,5 Moreover, CD4 + or CD8 + T cells which lose the CD28 molecule display potent effector functions with oversecretion of inflammatory cytokines IFN-γ and TNF-α. 20 Both MMSE and MOCA examinations showed significantly lower Depression was also a cofounder that influenced cognitive dysfunction in SLE.…”

Section: Discussionmentioning

confidence: 99%

“…Signs for the immunological consequences in the development of NPSLE syndromes are evidence of high titers of pro-inflammatory cytokines and chemokines that have been identified in the cerebrospinal fluid (CSF) of NPSLE patients, including interleukin (IL)-1, IL-6, IL-10, interferon (IFN)α, IFNγ, tumor necrosis factor (TNF)α, B-cell activating factor, and APRIL. 4,5 Some cytokines such as IL-10, TNF-α, IL-6, IFN-γ, IL-4, and IL-13 are also used as predictors that can expect the longer disease duration and poor outcome in NPSLE. 5 Although these findings show the importance of immune activation in NPSLE, whether lupus brain fog is a central nervous system manifestation of the disease that is mediated by an immune response mechanism deserves further research.…”

Section: Introductionmentioning

confidence: 99%

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Accelerated immune aging was correlated with lupus‐associated brain fog in reproductive‐age systemic lupus erythematosus patients

et al. 2020

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Aims: Cognitive impairment is common in systemic lupus erythematosus (SLE) patients with substantial adverse effects on function and quality of life. One hypothesis to understand the mechanisms of cognitive impairment in SLE is accelerated immunosenescence. The aim of this study is to observe the correlation between immunosenescence with cognitive impairment in patients with SLE. Methods: Sixty-one female SLE patient were measured for CD4 and CD8 T cellassociated senescence markers, including percentage of end-stage differentiated T cells (CD4 and CD8 T cells expressing CD57 + or loss of CD28 expression), of naïve T cells (CD4 + CD45RA + and CD8 + CD45RA + ), memory T cells (CD4 + CD45RO + and CD8 + CD45RO + ), and antigen-experienced T cells (CD4 + KLRG1 + and CD8 + KLRG1 + ) which were measured using flow cytometry. One hallmark of immunosenescence called immune risk profile (IRP) was defined by an inverted ratio of CD4 and CD8. Cognitive functions were measured by Mini-Mental State Examination (MMSE) and Montréal Cognitive Assessment (MOCA) questionnaire. Results: Thirty-six (59.1%) SLE patients who had IRP develop significantly lower attention and recall from both MMSE (P = .005 and P = .000) and MOCA (P = .017 and P = .000) examinations. Decreased visuospatial ability was also found in patients with IRP measured by MOCA (P = .046). There was a negative correlation between memory CD4 + CD45RO + T cells with recall and visuospatial domain (R = −0.204, P = .039 and R = −0.250, P = .033; respectively), and negative correlation between CD8 + CD28 -T cells with recall and attention domain (R = −0.249, P = .027 and R = −0.145, P = .048, respectively). Conclusion: Systemic lupus erythematosus patients develop an accelerated immunosenescence which contributes to cognitive dysfunction, especially in attention, recall, and visuospatial domains. K E Y W O R D S immunosenescence, lupus-associated brain fog, systemic lupus erythematosus | 621 KALIM et AL.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Accelerated immune aging was correlated with lupus‐associated brain fog in reproductive‐age systemic lupus erythematosus patients

et al. 2020

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“…Neuropsychiatric SLE (NPSLE) is a serious complication of SLE ( 84 ). Although the mechanism of NPSLE remains unclear, cytokines and chemokines, such as IFN-β and IFN-γ, are considered to be involved in the pathogenesis of NPSLE through the JAK/STAT signaling pathway ( 85 – 88 ). IFN-β-treated astrocyte in vitro was able to generate a large amount of chemokines, such as CCL2, CCL5, and CXCL10, and these chemokines can be negatively regulated by SOCS1 ( 89 ).…”

Section: Socs1 Signals Are Involved In Other End-organ Injuries In Slmentioning

confidence: 99%

Defective Suppressor of Cytokine Signaling 1 Signaling Contributes to the Pathogenesis of Systemic Lupus Erythematosus

Wang

Xia

2017

Front. Immunol.

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Systemic lupus erythematosus (SLE) is a complex autoimmune disease involving injuries in multiple organs and systems. Exaggerated inflammatory responses are characterized as end-organ damage in patients with SLE. Although the explicit pathogenesis of SLE remains unclear, increasing evidence suggests that dysregulation of cytokine signals contributes to the progression of SLE through the Janus kinase/signal transducer and activator of transcription (STAT) signaling pathway. Activated STAT proteins translocate to the cell nucleus and induce transcription of target genes, which regulate downstream cytokine production and inflammatory cell infiltration. The suppressor of cytokine signaling 1 (SOCS1) is considered as a classical inhibitor of cytokine signaling. Recent studies have demonstrated that SOCS1 expression is decreased in patients with SLE and in murine lupus models, and this negatively correlates with the magnitude of inflammation. Dysregulation of SOCS1 signals participates in various pathological processes of SLE such as hematologic abnormalities and autoantibody generation. Lupus nephritis is one of the most serious complications of SLE, and it correlates with suppressed SOCS1 signals in renal tissues. Moreover, SOCS1 insufficiency affects the function of several other organs, including skin, central nervous system, liver, and lungs. Therefore, SOCS1 aberrancy contributes to the development of both systemic and local inflammation in SLE patients. In this review, we discuss recent studies regarding the roles of SOCS1 in the pathogenesis of SLE and its therapeutic implications.

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“…In lupus, FGF2 is positively correlated with disease activity [52]. A recent study compared the protein levels of various growth factors in the cerebrospinal fluid (CSF) of lupus patients relative to subjects with disrupted BBB, such as MS. FGF2 was one of six upregulated genes that predicted lupus using a weighted algorithm [53]. …”

Section: Fgf System In Neurological Disordersmentioning

confidence: 99%

Dysregulated fibroblast growth factor (FGF) signaling in neurological and psychiatric disorders

Turner

Eren-Koçak

Inui³

et al. 2016

Seminars in Cell & Developmental Biology

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The role of the fibroblast growth factor (FGF) system in brain-related disorders has received considerable attention in recent years. To understand the role of this system in neurological and psychiatric disorders, it is important to identify the specific members of the FGF family that are implicated, their location and the various mechanisms they can be modulated. Each disorder appears to impact specific molecular players in unique anatomical locations, and all of these could conceivably become targets for treatment. In the last several years, the issue of how to target this system directly has become an area of increasing interest. To date, the most promising therapeutics are small molecule inhibitors and antibodies that modulate FGF receptor (FGFR) function. Beyond attempting to modify the primary players affected by a given brain disorder, it may prove useful to target molecules, such as membrane-bound or extracellular proteins that interact with FGF ligands or FGFRs to modulate signaling.

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Distinguishing the cerebrospinal fluid cytokine profile in neuropsychiatric systemic lupus erythematosus from other autoimmune neurological diseases

Cited by 39 publications

References 40 publications

Accelerated immune aging was correlated with lupus‐associated brain fog in reproductive‐age systemic lupus erythematosus patients

Accelerated immune aging was correlated with lupus‐associated brain fog in reproductive‐age systemic lupus erythematosus patients

Defective Suppressor of Cytokine Signaling 1 Signaling Contributes to the Pathogenesis of Systemic Lupus Erythematosus

Dysregulated fibroblast growth factor (FGF) signaling in neurological and psychiatric disorders

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