June 2024
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3 Reads
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
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June 2024
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3 Reads
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
May 2024
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9 Reads
Heliyon
Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system primarily mediated by CD4⁺ T helper cells. This study investigated the dynamic changes of natural killer (NK) cells and follicular T helper (Tfh) cells and their associations in relapsing-remitting MS patients. The findings revealed inverse relationships between NK cells and CD4⁺ T cells or Tfh cells. Specifically, CD56dim NK cells, not CD56bright NK cells, were negatively correlated with CD4⁺ T cells and Tfh cells. However, no significant correlations were found between NK cells and sNfL levels or EDSS scores. The ratio of CD56dim NK cells to circulating Tfh (cTfh) cells demonstrated superior discriminatory ability in distinguishing relapsing MS patients from healthy controls (HCs) and remitting patients, as determined by receiver operating characteristic (ROC) analysis. Following treatment with immunosuppressants or disease-modifying therapies (DMTs), a significant increase in the CD56dim NK/cTfh ratio was observed. These findings suggest that the CD56dim NK/cTfh ratio holds promise as a prognostic indicator for clinical relapse and treatment response in MS.
August 2023
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31 Reads
Background Multiple sclerosis (MS) has been considered to be a T cell-dependent autoimmune disease of the central nervous system (CNS), and so does the experimental autoimmune encephalomyelitis (EAE) model. Recent studies have revealed a specific subset of CD8 T cells, known as CD8 follicular T cells (CD8⁺CXCR5⁺ T), are involved in antiviral, anti-tumor immunity, and systemic autoimmunity. While the role of CD8⁺CXCR5⁺ T cells in MS and EAE remains unclear. Methods We detected CD8⁺CXCR5⁺ T cell frequency in the peripheral blood of relapsing-remitting MS patients and healthy controls by flow cytometry and analyzed its correlation with disease activity. To show the dynamic changes and locations of CD8⁺CXCR5⁺ T cells in secondary lymphoid organs and CNS from EAE mice, flow cytometry and multiplexed immunohistochemistry were performed. RNA-seq, co-culture experiments and in vivo adoptive transfer were then conducted to reveal the phenotypes and functions of CD8⁺CXCR5⁺ T cells. Results Expansion of CD8⁺CXCR5⁺ T cells in MS patients and EAE mice was detected during the acute phase. In relapsing MS patients, elevated frequencies of circulating CD8⁺CXCR5⁺ T cells were positively correlated with new gadolinium-enhancement lesions of CNS. In EAE mice, CD8⁺CXCR5⁺ T cells infiltrated in ectopic lymphoid structures of spinal cords and germinal centers of spleens were positively correlated with clinical score and highly expressed ICOS, CD40L, IL-21 and IL-6. In vitro co-culture experiments and CD8⁺CXCR5⁺ T-adoptive mice both confirmed the ability of CD8⁺CXCR5⁺ T cells to provide B cell help and contribute to disease progression. Conclusions CD8⁺CXCR5⁺ T cells which bridged cytotoxic T cells and B cells in MS might be a promising target for developing disease-modifying treatments in the future.
May 2023
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51 Reads
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1 Citation
Neurology Neuroimmunology & Neuroinflammation
Background and Objectives Existing evidence indicates anti-GABA B receptor encephalitis (GABA B R-E) seems to occur more commonly later in life, yet the age-associated differences in clinical features and outcomes are not well determined. This study aims to explore the demographic, clinical characteristics, and prognostic differences between late-onset and early-onset GABA B R-E and identify predictors of favorable long-term outcomes. Methods This is an observational retrospective study conducted in 19 centers from China. Data from 62 patients with GABA B R-E were compared between late-onset (aged 50 years or older) and early-onset (younger than 50 years) groups and between groups with favorable outcomes (modified Rankin scale (mRS) ≤ 2) and poor outcomes (mRS >2). Logistic regression analyses were applied to identify factors affecting long-term outcomes. Results Forty-one (66.1%) patients experienced late-onset GABA B R-E. A greater proportion of males, a higher mRS score at onset, higher frequencies of ICU admission and tumors, and a higher risk of death were demonstrated in the late-onset group than in the early-onset group. Compared with poor outcomes, patients with favorable outcomes had a younger onset age, a lower mRS score at onset, lower frequencies of ICU admission and tumors, and a greater proportion with immunotherapy maintenance for at least 6 months. On multivariate regression analysis, age at onset (OR, 0.849, 95% CI 0.739−0.974, p = 0.020) and the presence of underlying tumors (OR, 0.095, 95% CI 0.015−0.613, p = 0.013) were associated with poorer long-term outcomes, whereas immunotherapy maintenance for at least 6 months was associated with favorable outcomes (OR, 10.958, 95% CI 1.469−81.742, p = 0.020). Discussion These results demonstrate the importance of risk stratification of GABA B R-E according to age at onset. More attention should be paid to older patients especially with underlying tumors, and immunotherapy maintenance for at least 6 months is recommended to achieve a favorable outcome.
January 2023
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25 Reads
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4 Citations
Multiple Sclerosis and Related Disorders
Background Rituximab (RTX) is an extensively used off-label drug for multiple sclerosis (MS), whereas the induction and maintenance regimens vary widely among studies. Few data are available on efficacy and safety of repeated low-dose RTX therapy in MS patients. Objective This study aimed to evaluate the efficacy and safety of repeated low-dose RTX therapy for relapsing-remitting MS (RRMS), the most common form of MS affecting approximately 85% of patients. Methods Nine RRMS patients were enrolled and the medical records were retrospectively reviewed. RTX at 100 mg per week for three consecutive weeks was used as induction therapy. Maintenance therapy was reinfusions of RTX at 100 mg every 6 months during the first year, followed by 100 mg every 6 to 12 months. Main outcome measures included annualized relapse rate (ARR), expanded disability status scale (EDSS) score, and T2 lesion burden on MRI for evaluating the efficacy of low-dose RTX regimen. Meanwhile, adverse events (AEs) were recorded to assess the safety of repeated RTX infusions. Results All patients were females with an average onset age of 25.4 ± 6.7 years. The median disease duration before the first RTX infusion was 56 (range, 3–108) months and the median follow-up period was 30 (range, 15–40) months. No relapses were recorded in all patients after RTX therapy. Repeated low-dose RTX therapy resulted in a dramatic reduction of median ARR (pre-RTX vs post-RTX, 1.1 vs 0, p = 0.012), median EDSS score (2.0 vs 0, p = 0.007), and the number of T2 lesions on MRI (35.6 ± 18.0 vs 29.4 ± 18.1, p = 0.001). A total of 35 episodes of AEs occurred during repeated low-dose RTX therapy, and all of them were mild and transient. Conclusion Repeated low-dose RTX therapy is cost-effective for RRMS patients and shows a good safety profile. It may be a promising option for those having no access or poor response to first-line disease-modified drugs (DMDs), particularly in low- or middle-income countries.
January 2023
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10 Reads
July 2022
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65 Reads
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4 Citations
Brain Sciences
Background: Myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG) has been considered a diagnostic marker for patients with demyelinating disease, termed "MOG-IgG associated disorder" (MOGAD). Recently, the coexistence of MOG-IgG and other neuronal or glial antibodies has attracted extensive attention from clinicians. In this article, we systematically review the characteristics of MOG-IgG-related antibody coexistence syndrome. Methods: Two authors independently searched PubMed for relevant studies published before October 2021. We also manually searched the references of each related article. The appropriateness of the included studies was assessed by reading the titles, abstracts, and full texts if necessary. Results: Thirty-five relevant publications that met our inclusion criteria were finally included, of which fourteen were retrospective studies and twenty-one were case reports. A total of 113 patients were reported to show the coexistence of MOG-IgG and neuronal or glial antibodies. Additionally, 68.14% of patients were double positive for MOG-IgG and N-Methyl-D-Aspartate Receptor-IgG (NMDAR-IgG), followed by 23.01% of patients who were double positive for MOG-IgG and aquaporin4-IgG (AQP4-IgG). Encephalitis was the predominant phenotype when MOG-IgG coexisted with NMDAR-IgG, probably accompanied by imaging features of demyelination. Patients with dual positivity for MOG-IgG and AQP4-IgG experienced more severe disease and more frequent relapses. The coexistence of MOG-IgG and antibodies other than NMDAR-IgG and AQP4-IgG was extremely rare, and the clinical presentations were diverse and atypical. Except for patients who were double positive for MOG-IgG and AQP4-IgG, most patients with multiple antibodies had a good prognosis. Conclusions: MOG-IgG may coexist with neuronal or glial antibodies. Expanded screening for neuronal or glial antibodies should be performed in patients with atypical clinical and radiological features.
November 2021
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66 Reads
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6 Citations
BMC Neurology
Background and purpose: To summarize the clinical characteristics of patients with muscle-specific kinase antibody-associated myasthenia gravis (MuSK-MG) and to evaluate the therapeutic responses to different treatment regimes. Methods: Eighteen MuSK-MG patients admitted in our department between October 2017 and September 2020 were included. Clinical parameters were collected and the responses to different immunosuppressive drugs were assessed by MGFA Postintervention Status (MGFA-PIS). Meanwhile, the correlation between QMG scores and MuSK antibody titers were analyzed and MuSK antibody (MuSK-ab) titers were compared before and after therapy based on different immunosuppressive treatment regimes. Results: Female predominance (ratio of females to males, 15:3) was evident in the study population, with the average onset age of (40.28 ± 18.57) years and the median disease course of 30.50 months (interquartile range [IQR], 17.50-44.75 months). Ocular manifestation was the most common onset symptom (11/18; 61.11%), and mild symmetrical ptosis was most frequent. Bulbar symptoms had the highest incidence of 88.89% over the entire disease course. Abnormal responses to RNS test were recorded most frequently on the musculus deltoideus (83.33%). All patients were treated with prednisone (Pred) alone or plus azathioprine (AZA), tacrolimus (TAC) or low-dose rituximab (RTX), and 17 (94.44%) of them achieved a favorable outcome defined as minimal manifestation (MM) or better. In general, an obvious positive correlation between QMG score and MuSK-ab titer (r = 0.710, P < 0.001) were found in all patients. A more significant reduction of MuSK-ab titers was observed in patients receiving TAC or RTX plus Pred than those receiving AZA plus Pred. Conclusions: The prominent clinical manifestations of ocular and bulbar muscles involvements, together with abnormal RNS response mostly recorded on the musculus deltoideus and better efficacy associated with TAC or low-dose RTX plus Pred, provide a more exhaustive picture of MuSK-MG, particularly in Northwest China.
October 2021
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89 Reads
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19 Citations
Background and Objective: Myasthenia gravis (MG) is an autoimmune neuromuscular disease. Nearly 10–30% of patients with MG are refractory to conventional therapy. Rituximab (RTX), a monoclonal antibody targeting CD20, is increasingly used in autoimmune disorders. We performed a systematic review and meta-analysis to evaluate the effectiveness and safety of RTX for refractory MG. Methods: Studies published between January 1, 2000 and January 17, 2021 were searched in PubMed, EMBASE, Cochrane Library, and ClincalTrails.gov. Primary outcomes included proportion of patients achieving minimal manifestation status (MMS) or better and quantitative MG (QMG) score change from baseline. Secondary outcomes were glucocorticoids (GC) doses change from baseline and proportion of patients discontinuing oral immunosuppressants. Results: A total of 24 studies involving 417 patients were included in the meta-analysis. An overall 64% (95% confidence interval, 49–77%) of patients achieved MMS or better. The estimated reduction of QMG score was 1.55 (95% confidence interval, 0.88–2.22). The mean reduction of GC doses was 1.46 (95% confidence interval, 1.10–1.82). The proportion of patients discontinuing oral immunosuppressants was 81% (95% confidence interval, 66–93%). Subgroup analyses showed that the proportion of patients achieving MMS or better and discontinuing oral immunosuppressants was higher in MuSK-MG group than those in AChR-MG group. Improvement was more pronounced in patients with mild to moderate MG compared to those with severe MG. Moreover, the efficacy appeared to be independent of the dose of RTX. 19.6% of patients experienced adverse events, most of which were mild to moderate. Only one patient developed progressive multifocal leukoencephalopathy. Conclusions: RTX can alleviate the symptom of weakness, decrease QMG score and reduce the doses of steroids and non-steroid immunosuppressive agents in refractory MG. It is well-tolerated with few severe adverse events. Randomized controlled trials are urgently needed to study the efficacy of RTX in treating refractory MG and to identify the characteristics of patients who might respond well to RTX.
July 2018
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29 Reads
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8 Citations
Multiple Sclerosis and Related Disorders
Neuromyelitis optica (NMO), also known as Devic's disease, is a classical autoimmune disorder of the central nervous system (CNS). The relapsing-remitting disease course contributes to application of a variety of immunosuppressants to prevent further relapses after high-dose methylprednisolone pulse therapy for acute attacks. Azathioprine is one of the most widely used immunosuppressive drugs during the remission stage of NMO due to its good efficacy and favorable side-effect profile. Even if, enough attention should be paid to some rare but devastating adverse events, such as pellagra. Herein, we reported that a well-nourished patient experienced serious pellagra while receiving oral azathioprine for treating her NMO. Moreover, literature on azathioprine-induced pellagra was reviewed to raise concerns regarding patient safety.
... 72 Furthermore, a retrospective case series (n = 9) revealed that low-dose rituximab (100 mg every 6 months) showed cost-effective results and a good safety profile in Chinese patients with RRMS. 73 DMF and S1PRMs can be prescribed for treatment of patients with active inflammatory MS. There were no head-to-head clinical trials comparing the efficacy of teriflunomide, DMF, and S1PRMs. ...
January 2023
Multiple Sclerosis and Related Disorders
... Since Titulaer et al. first reported an overlapping syndrome of anti-NMDAR and anti-MOG antibodies (8), a growing number of cases have been documented, and their clinical characteristics have become more apparent. Previous reviews have identified several features of this condition, including its higher prevalence in young men (9)(10)(11)(12)(13); symptoms similar to anti-NMDAR encephalitis, such as psychiatric symptoms and seizures (10,12,13); complex imaging findings with features of both anti-NMDAR encephalitis and MOGAD (10,12,13); and a generally favorable functional prognosis (9)(10)(11)(12)(13), despite the tendency for recurrence (9)(10)(11)(12). Initial treatment often involves steroids. ...
July 2022
Brain Sciences
... 30 Actually, ocular involvement, including diplopia and ptosis, is also not uncommon in MuSK-MG either at onset or over a long disease course, although bulbar and respiratory symptoms are often emphasized. 26,27,39 Half of the DSP-MG patients in our cohort exhibited bulbar and respiratory involvement at nadir, although an even larger proportion of bulbar dysfunction was observed in MuSK-MG. However, only one case of DSP-MG experienced myasthenic crisis, indicating relatively mild conditions in our patients. ...
November 2021
BMC Neurology
... While there is accumulating evidence for its benefits in non-MuSK serotypes, its place in the treatment of anti-acetylcholine receptor positive (AChR +), and even more so in double seronegative (DSN) patients, remains less clear [2,3]. Experience so far is based on heterogenous data, often providing conflicting results [9][10][11][12]. ...
October 2021
... Iatrogenic NAD deficiency can also occur following the use of a drug treatment for other conditions than cancer, such as tuberculosis and HIV [70][71][72][73][74]. Isoniazid (INH), a drug used for tuberculosis prevention, forms adducts with NAD and NADP and prevents the absorption of dietary niacin. ...
July 2018
Multiple Sclerosis and Related Disorders
... Furthermore, IL-21 is also required for the complete generation of Tfh cells [42,43]. A small proportion of Tfh cells called circulating Tfh (cTfh) cells can be found in the peripheral blood, and they have been extensively associated with autoimmune diseases such as systemic lupus erythematosus (SLE) [44][45][46][47][48], (RA) [49][50][51], Sjögren's syndrome (pSS) [52][53][54][55][56] and multiple sclerosis (MS) [57,58]. Although Tfh cells had been the main CD4 + T cell subpopulation involved in maintaining the generation of autoantibodies, recent research has focused on a novel cell subpopulation that appears to be more closely associated with the pathogenesis of autoimmune diseases. ...
May 2018
... Cystatin F is an important regulator of cytolytic activity in both NK cells and T cells [54,55], and increased cystatin F levels correlate with reduced CTL cytotoxicity [56]. Increased CTL activity/ perforin secretion may also be contributing to the extensive spinal cord demyelination observed in the Cst7-/mice [87,88]. It is also important to mention that we did not detect changes in transcripts encoding anti-inflammatory cytokines IL-10, TGFb, and Annexin 1. Nonetheless, it is inevitable that germline ablation of Cst7 affects gene expression in other cells types specifically resident cells of the CNS e.g. ...
November 2017
Neurological Research
... Previous studies have shown increased prevalence of Tfh cells in CSF from patients with untreated MS [21,[23][24][25] and correlations between CSF Tfh cells and the IgG index [21]. Anti-CD20 therapy reduces both B and T cells in CSF [26][27][28][29], and studies have indicated a reduction of circulating Tfh cells [6,30,31], but differential effects on CSF Tfh cell subsets and Tfr cells remain elusive. ...
March 2017
... A recent study demonstrated that metastasis-associated protein 1 (MTA1), which is a chromatin modifier and transcriptional regulator, could be a factor linking ERα with apoptosis. The increase of MTA1 expression in mice after transient middle cerebral artery occlusion (tMCAO) promoted interactions between ERα and anti-apoptotic Bcl-2 which in turn diminished ischemia-induced brain damage [109]. In line, endogenous estrogen in proestrus protected female rats against I/R injury by an increase of ERα-dependent Bcl-2 expression [110]. ...
June 2016
Cell and Tissue Research