Brain MRI in patients with acute confusional state of diffuse psychiatric/neuropsychological syndromes in systemic lupus erythematosus

Abe, Gakuro; Kikuchi, Hirotoshi; Arinuma, Yoshiyuki; Hirohata, Shunsei

doi:10.1080/14397595.2016.1193966

Cited by 20 publications

(8 citation statements)

References 28 publications

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“…Of note, previous studies disclosed that abnormalities on MRI, serum IL-6 and serum anti-Sm significantly reduced the survival of patients with ACS. 26 In our study, 4 patients out of 8 patients with ACS with positive anti-GRP78 died, whereas 5 patients out of 20 patients with ACS with negative anti-GRP78 showed fatal outcome. Although the difference in mortality did not reach statistical significance in the present study, further studies with a larger number of patients would be required to identify such factors that would affect the outcome of patients with ACS, including serum anti-GRP78.…”

Section: Discussionmentioning

confidence: 46%

Elevation of serum anti–glucose-regulated protein 78 antibodies in neuropsychiatric systemic lupus erythematosus

et al. 2018

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ObjectiveRecent studies have demonstrated that autoantibodies directed against glucose-regulated protein 78 (GRP78) on endothelial cells promote blood–brain barrier (BBB) damages. The present study examined whether serum anti-GRP78 antibodies might be involved in the pathogenesis of neuropsychiatric SLE (NPSLE).MethodsSerum samples were obtained from 129 patients with SLE (58 patients with diffuse psychiatric/neuropsychological syndromes of NPSLE (diffuse NPSLE), 30 with neurological syndromes (focal NPSLE), 21 with lupus nephritis (LN), 20 without NPSLE or LN (SLE alone)), from 35 patients with non-SLE rheumatic diseases (non-SLE RD) and from 24 healthy controls (HC). Anti-GRP78 levels were measured with an ELISA, using recombinant GRP78 as antigens. Cerebrospinal fluid (CSF) samples were also obtained from 88 patients with NPSLE. The BBB function was evaluated by Q albumin ((CSF albumin/serum albumin)×103).ResultsSerum anti-GRP78 levels were significantly elevated in SLE compared with non-SLE RD or HC. There were no significant differences in serum anti-GRP78 levels among NPSLE, LN and SLE alone. Of note, serum anti-GRP78 levels were significantly higher in acute confusional state (ACS) than in non-ACS diffuse NPSLE (p=0.0001) or in focal NPSLE (p=0.0002). Finally, serum anti-GRP78 levels were significantly correlated with Q albumin (r=0.294, p=0.0054) in NPSLE.ConclusionThese results indicate that anti-GRP78 antibodies are associated with the development of diffuse NPSLE, especially ACS. Thus, the data suggest that anti-GRP78 antibodies might contribute to the development of ACS through the damages of BBB.

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Section: Discussionmentioning

confidence: 46%

Elevation of serum anti–glucose-regulated protein 78 antibodies in neuropsychiatric systemic lupus erythematosus

et al. 2018

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“…There is still an important question to be addressed in the future, that is, what are the molecular links between increased BBB leakage, microglia activation and inflammation? Previous studies have revealed a number of factors associated with neurological disorders in the circulating blood of SLE patients, including autoantibodies (anti-phospholipid, anti-ribosomal P and anti-DNA antibodies) and cytokines (IL-2, IL-6, IL-8, IL-10, IFN-α, and TNF-α) (Abe et al, 2017;DeGiorgio et al, 2001;Efthimiou and Blanco, 2009;Ho et al, 2016;Segovia-Miranda et al, 2015). Some of these immunological mediators may Fig.…”

Section: Discussionmentioning

confidence: 99%

Intracerebroventricular administration of lupus serum induces microglia activation and leukocyte adhesion in the cerebromicrovasculature of mice

Wang

et al. 2019

Journal of Neuroimmunology

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Background: Central nervous system (CNS) involvement is commonly seen in the patients with system lupus erythematosus (SLE). Mechanisms underlying CNS damage in SLE remain largely unknown. Accumulating evidence suggest that activation of microglia in CNS plays an important role in the inflammatory responses in neurological diseases. The aim of this study is to examine the involvement of microglia in the CNS inflammatory responses induced by circulating serum of SLE patients. Methods: We performed intracerebroventricular (ICV) injection of serums collected from SLE patients or healthy controls to mice, and examined phenotypic changes of microglia, the levels of cytokines, chemokine and adhesion molecules in the brain. Intravital microscopy was used to observe leukocyte rolling and adhesion in the cerebromicrovasculature. We further examined whether minocycline can block inflammatory responses induced by SLE serum. In vitro experiments were conducted to examine whether IgGs from the sera of SLE patients or healthy control can activate the primary cultured microglia. Results: We found that ICV injection of SLE serum increases morphological activation of microglia in the cortex and hippocampus. Inflammatory mediators including pro-inflammatory cytokines (IL-1, IL-6 and TNF-α), chemokine (CCL2 and CCL5) and adhesion molecules (P-selectin and ICAM-1) were significantly elevated in the brains of SLE-serum-treated mice. Using intravital microscopy, we demonstrated that SLE serum promotes leukocyte rolling and adhesion. Furthermore, suppression of microglia activation by systemically using minocycline could decrease the levels of inflammatory molecular, and prevent leukocyte rolling and adhesion. The in vitro experiments revealed that IgG from SLE sera could be engulfed by microglia and stimulated the microglia to secret pro-inflammatory cytokines. Conclusion: Our data suggest that the activation of microglia, which promotes leukocyte adhesion to the brain microvasculature, is an important pathological mechanism of CNS involvement in SLE.

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“…Thus, it is also concluded that serum IL‐6 is also a surrogate marker of the severity of NPSLE. In fact, previous studies disclosed that serum IL‐6 significantly reduced the survival of patients with ACS (18).…”

Section: Discussionmentioning

confidence: 99%

Role of Serum IL‐6 in Neuropsychiatric Systemic lupus Erythematosus

Hirohata

Kikuchi

2021

ACR Open Rheumatology

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Objective The present study was designed in order to elucidate the roles of serum interleukin 6 (IL‐6) in the pathogenesis in neuropsychiatric systemic lupus erythematosus (NPSLE). Methods Paired serum and cerebrospinal fluid (CSF) samples were obtained from 101 patients with SLE when they presented active neuropsychiatric manifestations (69 patients with diffuse psychiatric/neuropsychological syndromes [diffuse NPSLE] and 32 patients with neurologic syndromes or peripheral nervous system involvement [focal NPSLE]) and from 22 control patients without SLE with noninflammatory neurological diseases. The levels of albumin and IL‐6 in CSF and sera were measured by enzyme‐linked immunosorbent assay. Results Serum IL‐6 and CSF IL‐6 were elevated in NPSLE compared with non‐SLE controls. Among NPSLE, serum IL‐6 and CSF IL‐6 were significantly elevated in acute confusional state (ACS) compared with non‐ACS diffuse NPSLE (anxiety disorder, cognitive dysfunction, mood disorder, and psychosis) or focal NPSLE. Q albumin (CSF/serum albumin quotient) was also significantly higher in ACS than in the other two groups of NPSLE. Of note, serum IL‐6 (r = 0.2801, p = 0.0207), but not CSF IL‐6 (r = 0.1602, p = 0.1918), was significantly correlated with Q albumin in patients with diffuse NPSLE, including ACS and non‐ACS. Conclusion These results indicate that serum IL‐6 as well as CSF IL‐6 is involved in the pathogenesis of NPSLE. Moreover, it is suggested that serum IL‐6 might play a most important role in blood‐brain barrier breakdown in NPSLE.

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Brain MRI in patients with acute confusional state of diffuse psychiatric/neuropsychological syndromes in systemic lupus erythematosus

Abstract: These results demonstrate that patients with ACS with MRI abnormalities have more severe diseases, resulting in poorer prognoses. The data also indicate that anti-Sm is involved in the development of MRI abnormalities in ACS.

Cited by 20 publications

References 28 publications

Elevation of serum anti–glucose-regulated protein 78 antibodies in neuropsychiatric systemic lupus erythematosus

Elevation of serum anti–glucose-regulated protein 78 antibodies in neuropsychiatric systemic lupus erythematosus

Intracerebroventricular administration of lupus serum induces microglia activation and leukocyte adhesion in the cerebromicrovasculature of mice

Role of Serum IL‐6 in Neuropsychiatric Systemic lupus Erythematosus

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