Th17 cells were recruited and accumulated in the cerebrospinal fluid and correlated with the poor prognosis of anti-NMDAR encephalitis

Zeng, Chaosheng; Chen, Lin; Chen, Bocan; Cai, Yi; Li, Pengxiang; Yan, Liang; Zeng, Dehua

doi:10.1093/abbs/gmy137

Cited by 28 publications

(50 citation statements)

References 44 publications

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“…In this respect, the correlation between anti-NMDAR antibodies and clinical course is unclear, 31,32 and the correlation of disease severity and relapse with other markers, such as C-X-C motif chemokine ligand 13 (CXCL13), C-X-C motif ligand 10 (CXCL10), Fas, Fas ligand, T-helper cell 17 (Th17), B cell activating factor from the tumor necrosis factor family (BAFF), and a proliferationinducing ligand (APRIL) is being investigated. [33][34][35][36][37][38][39] This dissociation between disease course (monophasic vs relapsing) and neurological outcome (mRS) at final followup is an interesting and counterintuitive finding. This result is limited by the statistically different length of follow-up between monophasic and relapsing patients (median 84mo and 32mo respectively), although it is mirrored by a previous analysis of relapses in anti-NMDAR encephalitis, with similar discrepancies in the length of follow-up in the two subgroups.…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, it is unclear how long the inflammatory component of disease lasts. In this respect, the correlation between anti‐NMDAR antibodies and clinical course is unclear, and the correlation of disease severity and relapse with other markers, such as C‐X‐C motif chemokine ligand 13 (CXCL13), C‐X‐C motif ligand 10 (CXCL10), Fas, Fas ligand, T‐helper cell 17 (Th17), B cell activating factor from the tumor necrosis factor family (BAFF), and a proliferation‐inducing ligand (APRIL) is being investigated …”

Section: Discussionmentioning

confidence: 99%

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Relapse risk factors in anti‐N‐methyl‐D‐aspartate receptor encephalitis

Nosadini

Granata²,

Matricardi³

et al. 2019

Develop Med Child Neuro

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Aim To identify factors that may predict and affect the risk of relapse in anti‐N‐methyl‐D‐aspartate receptor (NMDAR) encephalitis. Method This was a retrospective study of an Italian cohort of patients with paediatric (≤18y) onset anti‐NMDAR encephalitis. Results Of the 62 children included (39 females; median age at onset 9y 10mo, range 1y 2mo–18y; onset between 2005 and 2018), 21 per cent relapsed (median two total events per relapsing patient, range 2–4). Time to first relapse was median 31.5 months (range 7–89mo). Severity at first relapse was lower than onset (median modified Rankin Scale [mRS] 3, range 2–4, vs median mRS 5, range 3–5; admission to intensive care unit: 0/10 vs 3/10). At the survival analysis, the risk of relapsing was significantly lower in patients who received three or more different immune therapies at first disease event (hazard ratio 0.208, 95% confidence interval 0.046–0.941; p=0.042). Neurological outcome at follow‐up did not differ significantly between patients with relapsing and monophasic disease (mRS 0–1 in 39/49 vs 12/13; p=0.431), although follow‐up duration was significantly longer in relapsing (median 84mo, range 14–137mo) than in monophasic patients (median 32mo, range 4–108mo; p=0.002). Interpretation Relapses may occur in about one‐fifth of children with anti‐NMDAR encephalitis, are generally milder than at onset, and may span over a long period, although they do not seem to be associated with severity in the acute phase or with outcome at follow‐up. Aggressive immune therapy at onset may reduce risk of relapse. What this paper adds Relapses of anti‐N‐methyl‐D‐aspartate receptor encephalitis may span over a long period. Relapses were not associated with severity in the acute phase or outcome at follow‐up. Aggressive immune therapy at onset appears to decrease risk of relapse.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Relapse risk factors in anti‐N‐methyl‐D‐aspartate receptor encephalitis

Nosadini

Granata²,

Matricardi³

et al. 2019

Develop Med Child Neuro

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“…Gut microbiota can modulate the immune response in a variety of ways, such as affecting antigen presentation and regulating the production of cytokines and the function of T lymphocytes 33 . We further investigated the effects of FMT on T cell responses which play an important role in regulation and prognosis of anti-NMDAR encephalitis immune damage 34 . The Th17 cells were also accumulated in the CSF of anti-NMDAR encephalitis patients than that of control individuals 34 .…”

Section: Discussionmentioning

confidence: 99%

“…We further investigated the effects of FMT on T cell responses which play an important role in regulation and prognosis of anti-NMDAR encephalitis immune damage 34 . The Th17 cells were also accumulated in the CSF of anti-NMDAR encephalitis patients than that of control individuals 34 . We found that the Th17 responses in the SI LP and spleen were increased in anti-NMDAR encephalitis FMT mice, while Treg response was not affected.…”

Section: Discussionmentioning

confidence: 99%

Fecal microbiota transplantation from patients with autoimmune encephalitis modulates Th17 response and relevant behaviors in mice

Chen

Shen

et al. 2020

Cell Death Discov.

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The significance of the microbiota-gut-brain axis has been increasingly recognized as a major modulator of autoimmunity. Here, we aim to characterize the gut microbiota of a large cohort of treatment-naïve anti-N-methyl-Daspartate receptor (anti-NMDAR) encephalitis patients relative to that of healthy controls (HCs). Relative to HCs, anti-NMDAR encephalitis patients had a decreased microbiome alpha-diversity index, marked disturbances of gut microbial composition and intestinal permeability damage. Disturbed microbiota in anti-NMDAR encephalitis patients might be linked with different clinical characteristics. Imputed KEGG analysis revealed perturbations of functional modules in the gut microbiomes of anti-NMDAR encephalitis. Compared to HCs, microbiota-depleted mice receiving fecal microbiota transplantation (FMT) from anti-NMDAR encephalitis patients had hypersensitivity and cognitive impairment. Furthermore, anti-NMDAR encephalitis FMT mice showed altered T cells in the spleen and small intestine lamina propria with an increased Th17 cells. Overall, this study first suggests that the anti-NMDAR encephalitis microbiome itself can influence neurologic, Th17 response and behavioral function. The gut microbiota is a potential therapeutic target for anti-NMDAR encephalitis.

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“…The increase in OPN have been demonstrated in many inflammatory autoimmune diseases, such as multiple sclerosis, glomerulonephritis, Crohn's disease, and systemic lupus erythematosus (SLE) (19,(28)(29)(30)(31), which suggests that OPN plays a significant role in the pathogenesis of these inflammatory autoimmune disease. In fact, many researches have demonstrated that the OPN gene knockout animal could suffer less from the inflammation of autoimmune and non-immune diseases (19,(32)(33)(34)(35)(36)(37).…”

Section: Discussionmentioning

confidence: 99%

Cerebrospinal Fluid Osteopontin and Inflammation-Associated Cytokines in Patients With Anti-N-Methyl-D-Aspartate Receptor Encephalitis

et al. 2020

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Anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis is an autoimmune neurological disorder. Osteopontin (OPN) is a secreted multifunctional phosphorylated glycoprotein that regulates various autoimmune and inflammatory diseases, but its diagnostic and prognostic values in anti-NMDAR encephalitis patients remain elusive. This retrospective study aimed to determine the levels of OPN and related cytokines in cerebrospinal fluid (CSF) of anti-NMDAR encephalitis patients and to assess their influence on disease severity so as to evaluate their efficacy as biomarkers for diagnosis and prognosis. CSF samples from 33 anti-NMDAR encephalitis, 13 viral encephalitis, and 21 controls were collected. All CSF were tested for levels of OPN and inflammation-associated cytokines [interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-α] via ELISA. In addition, 15 anti-NMDAR encephalitis patients without follow-up relapse were reexamined for these four parameters 3 months later. The clinical status was evaluated by modified Rankin Scale (mRS) scores. Results showed that the CSF levels of these cytokines were increased in anti-NMDAR encephalitis patients compared to controls but not viral encephalitis patients. Their levels were decreased in remission compared with that in acute stage. Moreover, CSF OPN positively correlated with IL-6, white blood cell (WBC) counts, and C-reactive protein (CRP) levels in anti-NMDAR encephalitis patients. However, no associations were found between OPN or related cytokines and mRS scores in acute stage in anti-NMDAR encephalitis patients. Overall, CSF OPN and related cytokines were increased when anti-NMDAR encephalitis patients are in acute stage and decreased in remission, suggesting the underlying neuro-inflammatory process in this disease. However, they are not qualified with diagnostic or prognostic value.

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Th17 cells were recruited and accumulated in the cerebrospinal fluid and correlated with the poor prognosis of anti-NMDAR encephalitis

Cited by 28 publications

References 44 publications

Relapse risk factors in anti‐N‐methyl‐D‐aspartate receptor encephalitis

Relapse risk factors in anti‐N‐methyl‐D‐aspartate receptor encephalitis

Fecal microbiota transplantation from patients with autoimmune encephalitis modulates Th17 response and relevant behaviors in mice

Cerebrospinal Fluid Osteopontin and Inflammation-Associated Cytokines in Patients With Anti-N-Methyl-D-Aspartate Receptor Encephalitis

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