CSF chemokine alterations related to the clinical course of amyotrophic lateral sclerosis

Tateishi, Takahisa; Yamasaki, Ryo; Tanaka, Masahito; Matsushita, Takuya; Kikuchi, Hitoshi; Isobe, Noriko; Ohyagi, Yasumasa; Kira, Jun Ichi

doi:10.1016/j.jneuroim.2010.03.004

Cited by 96 publications

(112 citation statements)

References 32 publications

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“…Nevertheless, CCR1 and CCR5 are receptors of MIP‐1α, which differ from those of MCP‐1 and may explain the differential effects between MIP‐1α and MCP‐1, although the complex relationship between chemokine and receptor is still vague. In the light of previous results demonstrating a correlation between MCP‐1 levels and disease severity (Tateishi et al., 2010), our study suggests that MCP‐1 has a predictive value for ALS progression and is possibly neurotoxic. In addition, similar conclusions were reached in our previous report that MIP‐1α is likely neuroprotective and possibly can monitor disease progression (Yang et al., 2016).…”

Section: Discussionmentioning

confidence: 63%

“…In our study, elevated interleukin levels comprising IL‐2, IL‐6, IL‐10, IL‐15, and IL‐17 were noted in the serum from ALS patients, whereas only IL‐15 and IL‐17 were clearly increased in the CSF. One possible explanation for the difference observed from the CSF and serum is that IL‐2, IL‐6, and IL‐10 might have a limited input in central nervous system (CNS) during the inflammatory process; as one previous study has shown, these cytokines are at similar levels in the CSF of ALS patients and control subjects (Tateishi et al., 2010). Furthermore, even IL‐2 and IL‐10 could not be detected in the CSF of ALS patients (Holmoy, Roos, & Kvale, 2006).…”

Section: Discussionmentioning

confidence: 99%

“…In our study, we could not detect any significant difference in the CSF between ALS patients and control subjects, nor was there any correlation with either disease progression or prognosis. Although elevated G‐CSF and GM‐CSF in the CSF were noted in several studies (Mitchell et al., 2009; Tateishi et al., 2010), their predictive and therapeutic values in ALS were also preliminarily evaluated (Su et al., 2013; Zhang et al., 2009). Differences in race or patient selection among the studies may be cause of these discrepancies.…”

Section: Discussionmentioning

confidence: 99%

“…Here, elevated IFN‐γ levels represented an active immune response in the CNS and periphery, which is in accordance with a previous report (Tateishi et al., 2010). Importantly, our analyses in correlation and survival implied that IFN‐γ is a potential biomarker that can distinguish ALS patients from control subjects, monitor progression and predict the prognosis of patients with ALS.…”

Section: Discussionmentioning

confidence: 99%

“…Most of these studies have examined changes of individual biomarkers that might distinguish patients with ALS from healthy control subjects (Lu et al., 2015; Takahashi et al., 2015), but it is likely more appropriate to identify panels of biomarkers rather than focusing on a single factor to increase their specificity to ALS. Some studies were limited by the number of samples in the analysis (Turner et al., 2013), and some chose a different control population into the study (Tateishi et al., 2010). In addition, a panel of biomarkers has been detected in either the CSF or serum in some recent studies, but they were either more concerned with a diagnosis rather than a clinically relevant prognosis (Gray et al., 2015; Kuhle et al., 2009; Lawton et al., 2012) or only measuring factors either the CSF or serum (Ehrhart et al., 2015; Mitchell et al., 2009).…”

Section: Introductionmentioning

confidence: 99%

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Evaluating the levels of CSF and serum factors in ALS

et al. 2017

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ObjectivesThe aim of this study was to identify CSF and serum factors as biomarkers that may aid in distinguishing ALS patients from control subjects and predicting ALS progression as well as prognosis.MethodsSerum and CSF samples from 105 patients with ALS and 56 control subjects were analyzed for 13 factors using ELISA. The revised ALS functional rating scale (ALSFRS‐r) was used to evaluate the overall functional status of ALS patients, and we also followed up with ALS patients either by phone or with clinic visits for five years after enrollment in this study. Finally, we examined the correlations between factor levels and various clinical parameters and evaluated the predictive value for prognosis through a multivariate statistic model.ResultsA total of eight factors were obviously elevated in CSF, and twelve markers were increased in serum. In the correlation analyses, there were trends toward higher bFGF, VEGF, MIP‐1α levels in ALS with a longer disease duration and slower disease progression in both CSF and serum. Higher MCP‐1 levels were associated with worse disease severity and faster progression, and the IFN‐γ levels were positively associated with disease progression in either CSF or serum. Finally, a better prognosis was observed with higher levels bFGF in CSF and VEGF in CSF and serum; conversely, patients with higher levels of IFN‐γ in the CSF had shorter overall survival.ConclusionsWe demonstrated that a factor profile of ALS patients is distinct from control subjects and may be useful in clinical practice and therapeutic trials.

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Section: Discussionmentioning

confidence: 63%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Evaluating the levels of CSF and serum factors in ALS

et al. 2017

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Amyotrophic Lateral Sclerosis and Primary Lateral Sclerosis

2017

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Intrathecal cytokine profile in neuropathy with anti‐neurofascin 155 antibody

Ogata

Yamasaki

et al. 2019

Ann Clin Transl Neurol

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authors are contributed equally to this manuscript. AbstractObjective: To characterize the CSF cytokine profile in chronic inflammatory demyelinating polyneuropathy (CIDP) patients with IgG4 anti-neurofascin 155 (NF155) antibodies (NF155 + CIDP) or those lacking anti-NF155 antibodies (NF155 À CIDP). Methods: Twenty-eight CSF cytokines/chemokines/growth factors were measured by multiplexed fluorescent immunoassay in 35 patients with NF155 + CIDP, 36 with NF155 À CIDP, and 28 with non-inflammatory neurological disease (NIND). Results: CSF CXCL8/IL-8, IL-13, TNF-a, CCL11/ eotaxin, CCL2/MCP-1, and IFN-c were significantly higher, while IL-1b, IL-1ra, and G-CSF were lower, in NF155 + CIDP than in NIND. Compared with NF155 À CIDP, CXCL8/IL-8 and IL-13 were significantly higher, and IL-1b, IL-1ra, and IL-6 were lower, in NF155 + CIDP. CXCL8/IL-8, IL-13, CCL11/eotaxin, CXCL10/IP-10, CCL3/MIP-1a, CCL4/MIP-1b, and TNF-a levels were positively correlated with markedly elevated CSF protein, while IL-13, CCL11/eotaxin, and IL-17 levels were positively correlated with increased CSF cell counts. IL-13, CXCL8/IL-8, CCL4/MIP-1b, CCL3/MIP-1a, and CCL5/RANTES were decreased by combined immunotherapies in nine NF155 + CIDP patients examined longitudinally. By contrast, NF155 À CIDP had significantly increased IFNc compared with NIND, and exhibited positive correlations of IFN-c, CXCL10/ IP-10, and CXCL8/IL-8 with CSF protein. Canonical discriminant analysis of cytokines/chemokines revealed that NF155 + and NF155 À CIDP were separable, and that IL-4, IL-10, and IL-13 were the three most significant discriminators. Interpretation: Intrathecal upregulation of type 2 helper T (Th2) cell cytokines is characteristic of IgG4 NF155 + CIDP, while type 1 helper T cell cytokines are increased in CIDP regardless of the presence or absence of anti-NF155 antibodies, suggesting that overproduction of Th2 cell cytokines is unique to NF155 + CIDP.

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CSF chemokine alterations related to the clinical course of amyotrophic lateral sclerosis

Cited by 96 publications

References 32 publications

Evaluating the levels of CSF and serum factors in ALS

Evaluating the levels of CSF and serum factors in ALS

Amyotrophic Lateral Sclerosis and Primary Lateral Sclerosis

Intrathecal cytokine profile in neuropathy with anti‐neurofascin 155 antibody

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