Chinese Multiple Sclerosis Patients Research Articles

Multi-omics profiling reveals peripheral blood biomarkers of multiple sclerosis: implications for diagnosis and stratification.

Multiple sclerosis (MS), a chronic autoimmune disorder marked by demyelination in the central nervous system, is exceptionally uncommon in China, and remains poorly understood in terms of its peripheral blood manifestations. We conducted a cohort study comprising 39 MS patients and 40 normal controls (NC). High-dimensional mass cytometry, protein arrays, and targeted metabolomics were utilized to profile immune subsets, proteins, and metabolites in blood. Differences in multi-omics signatures were scrutinized across varying MS subtypes. Immune profiling demonstrated an elevation in various B cell subsets and monocytes, alongside a reduction in dendritic cells among MS patients. Proteomic data revealed a downregulation in neurotrophic and tissue repair proteins. Metabolomic assessment showed a noted decrease in anti-inflammatory molecules and sphingolipids. Integrated analysis identified distinct molecular patterns distinguishing MS from controls. Additionally, multi-omics differences among different MS subtypes were uncovered. Notably, hippuric acid levels was consistently lower in MS subgroups with greater disease severity. This study represents the pioneering exploration of multi-omics in Chinese MS patients, presenting a comprehensive view of the peripheral blood changes in MS. Our study underscores the robust capability of multi-omics assessments in identifying peripheral blood biomarkers that delineate the varied clinical presentation, and facilitates future development of biomarkers and targeted therapeutic interventions in MS.

Differences in physical, mental, and social functions between males and females in multiple sclerosis: A multicenter cross-sectional study in China

Background Sex-specific differences in multiple sclerosis (MS) have been recognized, but few were known about how sex influences the characteristics of MS in Asian and the social burden of MS. This study aimed to investigate the symptoms, mental health, and social functions of Chinese MS patients and find differences between sexes.Methods MS patients were enrolled from January 2004 to September 2018. A questionnaire was distributed by 47 medical centers. Patients’ physical symptoms, negative emotions, interpersonal communication, social intercourse, employment condition, and suicidal thoughts and behavior were collected. Patients were asked to fill in the questionnaire independently and undergo Expanded Disability Status Scale (EDSS) measurement. Unpaired t-tests between sexes were conducted for normally distributed continuous variables. Mann-Whitney u-tests were conducted for non-normally distributed data. Chi-square tests, Fisher exact tests and rank sum tests were performed for categorical variables.Results 931 patients were enrolled and 631 were female. Frequency of fatigue and pain were higher in female MS patients (P<0.05), while male patients complained more weakness, diplopia, sexual dysfunction, and micturition and defecation dysfunction (P<0.05). Females were more likely to experience sadness and helplessness than males (P<0.05) while males were more likely to experience nonacceptance than females (P<0.05). MS had a worse influence on male patients in relationships with family and friends (P<0.05). The employment rate of MS patients was 39.31%. The frequency of suicidal attempt was 2.36%, which was higher than general population.Conclusions The study provided evidence that characteristics of MS were different between males and females, and influence in mental and social function was a common problem among MS patients. More attention should be paid to the mental health and social function of MS patients.

Impaired cognition is related to microstructural integrity in relapsing remitting multiple sclerosis.

BackgroundCognitive impairment is common in multiple sclerosis (MS). However, the relationship between cognitive deficits and microstructural abnormalities in Chinese MS patients remains unclear. We aimed to investigate the importance of microstructural abnormalities and the associations with cognitive impairment in Chinese MS patients.MethodsThree‐dimensional T1‐weighted magnetic resonance imaging (MRI) scans were obtained from 36 relapsing remitting MS patients. Diffusion tensor imaging (DTI) scans were acquired for 29 (81%) patients. Cognitive impairment was assessed using a comprehensive neuropsychological battery. Patients were classified into cognitively impaired (CI) group and cognitively preserved (CP) group. Using volBrain and FSL software, we assessed white matter lesion burden, white matter (WM) and gray matter (GM) volumetric as well as microstructural diffusivity. MRI variables explaining cognitive impairment were analyzed.ResultsFifteen (42%) patients were classified as CI. Verbal learning and memory was the most commonly impaired domain (n = 16, 44%). CI patients had lower mean skeleton fractional anisotropy (FA) value than CP patients (275.45 vs. 283.61 × 10−3, P = 0.023). The final predicting model including demographic variables and global skeleton mean diffusivity (MD) explained 43.6% of variance of the presence of cognitive impairment (β = 0.131, P = 0.041). CI patients showed a widespread change of microstructural integrity comparing to CP patients, which was rarely overlapping with lesion probability map. Microstructural abnormalities in corpus callosum were associated with performance in verbal learning and memory, processing speed and selective attention (P < 0.05).ConclusionLoss of microstructural integrity demonstrated by DTI helps explain cognitive dysfunction in Chinese MS patients.

Glucocorticoid receptor mutations and clinical sensitivity to glucocorticoid in Chinese multiple sclerosis patients

BackgroundGlucocorticoid (GC) is the first-line therapy in acute attacks of multiple sclerosis (MS), but its efficacy is individually variable and may be associated with glucocorticoid receptor (GR) gene.ObjectiveTo establish the association between GR gene sequence and clinical GC sensitivity in Chinese MS patients. And to investigate the expression differences of serum GRα and FK506 binding protein 5 (FKBP5) in GC responders and non-responders.Materials and methodsCoding exons 2–9 of the GR gene from 97 MS patients were sequenced. We performed ELISA to detect serum GRα and FKBP5 before the GC impulse therapy in patients with different GC sensitivities (according to the EDSS changes before and after the GC medication).ResultsSeven new mutations were located in exon 2, but the presence or absence of mutations was not associated with the response to GC therapy (P = 0.416). The GC-sensitive patients had higher GRα (P = 0.011) but lower FKBP5 (P = 0.025) levels in the serum.ConclusionsThe GR mutations detected in our study were not associated with the response to GC in Chinese MS patients. Higher GRα and lower FKBP5 levels in the serum might predict the response to GC, which may provide potential therapeutic target for GC-resistant patients with acute MS attack.

Homocysteine, vitamin B12, and folate levels in patients with multiple sclerosis in Chinese population: A case-control study and meta-analysis

BackgroundCurrent studies suggested discrepancies on the correlations between multiple sclerosis (MS) and blood levels of homocysteine (Hcy), vitamin B12 (VB12), and folate. We performed a case-control study and meta-analysis to help resolve the controversy of these lab values in Chinese patients with MS. MethodsWe recruited 80 Chinese MS patients, 86 age/sex matched neurological controls (patients with peripheral vertigo or sleep disorders), and 80 age- and sex-matched healthy controls. Serum Hcy levels were measured using flourimetric high-performance liquid chromatography, serum levels of VB12 and folate using immune assay. A literature search of PubMed, Embase, Web of Science, Chinese National Knowledge Infrastructure, Wanfang, and SinoMed was conducted for case-control studies with pure Chinese populations published up to March 16, 2019. The effective size was estimated by the pooled standardized mean difference (SMD) and associated 95% confidence interval (CI). ResultsThe case-control study results suggest higher Hcy levels (mean ± SD) and frequency of hyperhomocysteinemia in the Chinese MS cases than control groups (all p < 0.001), lower for VB12 levels (mean ± SD, p = 0.043 or 0.039). No significant difference was observed for levels of folate (mean ± SD, both p > 0.05), and for frequency of folate or VB12 deficiency (all p > 0.05). Analysis of pooled SMDs and 95% CIs suggested increased Hcy levels in Chinese MS patients (SMD: 2.31, 95% CI: 1.33–3.28, p < 0.001), and in relapsing or remitting cases relative to controls (SMD: 0.94 or 0.85, 95% CI: 0.49–1.39 or 0.35–1.34, both p < 0.001). The meta-analysis results also suggested reduced VB12 levels in Chinese MS patients (SMD: −0.30, 95% CI: −0.46–0.14, p < 0.001), and in relapsing MS patients compared to controls (SMD: −0.31, 95% CI: −0.47–0.15, p < 0.001), while no statistical difference for cases in remission. No significant difference was observed for levels folate in all comparisons. ConclusionPatients with MS tend to have increased blood Hcy levels compared to controls. MS patients of Chinese origin and those in relapse may have decreased levels of VB12. Hcy and VB12 may contribute to pathogenesis of the disease, and VB12 may correlate with MS relapse.

Gut dysbiosis and lack of short chain fatty acids in a Chinese cohort of patients with multiple sclerosis

BackgroundRecent studies, mostly conducted in Western countries, showed that gut microbes are involved in the pathogenesis of multiple sclerosis (MS). ObjectiveThe aim of this study was to investigate whether gut dysbiosis is relevant to the initiation and progression of MS in a Chinese population. MethodsNext-generation sequencing (NGS) and gas chromatography (GC) were integrated and used to compare the fecal bacterial communities and the short-chain fatty acid (SCFA) levels among relapsing-remitting MS (RRMS) patients (n = 34), neuromyelitis optica spectrum disorder (NMOSD) patients (n = 34), and healthy controls (HCs) (n = 34). T-cell profile analyses were performed by flow cytometry for MS patients and matched controls (n = 12). Results(1) The gut microbiome of MS patients was characterized by an increase of Streptococcus and a decrease of Prevotella_9; additionally, compared to NMOSD patients, Prevotella_9 was found to be much more abundant in MS patients. (2) A striking depletion of fecal acetate, propionate, and butyrate was observed in MS patients compared to HCs. (3) The abundance of Streptococcus was negatively correlated with the proportion of pTregs (P < 0.05) and positively correlated with Th17 cells (P < 0.05) in the peripheral blood, while the abundance of Prevotella_9 was negatively correlated with the Th17 cell frequency (P < 0.01), and the fecal SCFA level was positively correlated with pTreg frequency (P < 0.05). ConclusionsGut dysbiosis and a lack of SCFAs exist in Chinese MS patients, which might be related to an aberrant immune response of MS; this relationship may have a diagnostic and therapeutic value for patients with MS.

Variant of EOMES Associated with Increasing Risk in Chinese Patients with Relapsing-remitting Multiple Sclerosis.

Background:Multiple sclerosis (MS) is a common central nervous system autoimmune disorder. Increasing number of genome-wide association study (GWAS) analyses hint that MS is strongly associated with genetics. Unfortunately, almost all the GWAS analyses were Caucasian population based. Numbers of risk loci might not be replicated in Chinese MS patients. Hence, we performed a MassArray Assay to genotype the previously reported variants located in the transcription regulation genes in order to elucidate their role in the Chinese MS patients.Methods:One hundred and forty-two relapsing-remitting MS (RRMS) patients and 301 healthy controls were consecutively collected from September 2, 2008, to June 7, 2013, as stage 1 subjects. Eight reported transcription regulation-related single-nucleotide polymorphisms (SNPs) were genotyped using the Sequenom MassArray system. In stage 2, another 44 RRMS patients and 200 healthy controls were consecutively collected and Sanger sequenced from April 7, 2015, to June 29, 2017, for the validation of positive results in stage 1. Differences in allele and genotype frequencies between patients and healthy controls, odds ratios, and 95% confidence intervals were calculated with the Chi-square test or Fisher's exact test. Hardy-Weinberg equilibrium was tested also using the Chi-square test.Results:In stage 1 analysis, we confirmed only one previously reported risk variant, rs11129295 in EOMES gene. We found that the frequency of T/T genotype was much higher in MS group (χ2 = 10.251, P = 0.005) and the T allele of rs11129295 increased the risk of MS (χ2 = 10.022, P = 0.002). In stage 2 and combined analyses, the T allele of rs11129295 still increased the risk of MS (χ2 = 4.586, P = 0.030 and χ2 = 16.378, P = 5.19 × 10−5, respectively).Conclusions:This study enhances the knowledge that the variant of EOMES is associated with increasing risk in Chinese RRMS patients and provides a potential therapeutic target in RRMS.

Multiple sclerosis risk pathways differ in Caucasian and Chinese populations

Large-scale genome-wide association study (GWAS) datasets provide strong support for investigations of the mechanisms underlying multiple sclerosis (MS) by using pathway analysis methods. In our recent study, we conducted a three-stage pathway analysis of GWAS and expression datasets. After identifying 15 shared MS pathways in separate MS GWAS datasets, we found that dysregulated MS genes were significantly enriched in 10 of the 15 MS risk pathways. Evidence showed that 17%–30% of genes are differentially expressed among individual ethnic populations. We then verified the potential disruption of genes in the 10 MS risk pathways cited above in Chinese MS patients. Here, we investigated potential up- and down-regulation of 42 MS genes in these 10 MS risk pathways using 132 Chinese MS patients and 76 healthy control subjects. We then identified 31 differentially expressed genes in Chinese MS patients compared to healthy control subjects. Moreover, the expression patterns of 28 of these genes were consistent with those obtained from Caucasian (European and American) MS patients, although 14 genes differed from the latter group's. Our results provide clinically useful clues about the link between these risk genes and MS susceptibility in the Chinese population.

MicroRNA Expression Aberration in Chinese Patients with Relapsing Remitting Multiple Sclerosis

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease that is caused by an abnormal immune system that attacks the central nervous system. MicroRNAs (miRNAs) are known to play essential roles in the immune system. Most of the previous studies about miRNA dysregulation in MS have focused on European populations. In the present study, the miRNA expression profiles associated with Chinese MS patients are investigated. Here, human miRNA expression profiling experiments were performed on the peripheral blood mononuclear leukocytes from ten MS patients and ten healthy controls. Nine overexpressed and six underexpressed miRNAs were found. The 15 miRNAs were validated independently in a second cohort of 40 MS patients and 40 controls by real-time PCR; six miRNAs were significantly abnormally expressed, and principal component analysis of six miRNAs indicated that the MS patients could be clearly differentiated from the healthy controls based on the miRNA expression patterns. This study provided the indications of abnormal miRNA expression patterns in the peripheral blood mononuclear leukocytes of Chinese MS patients. The potential roles of these differentially expressed miRNAs as MS biomarker and in pathogenesis need to be investigated in future studies.

An analysis of typical and atypical MRI findings of brain lesions in multiple sclerosis: a 82 cases report

Objective To analyse the typical and atypical magnetic resonance imaging (MRI) findings of brain multiple sclerosis (MS) lesions in Chinese MS patients. Methods MRI findings of 82 Chinese MS patients who fulfilled McDonald criteria were reviewed retrospectively. The analysis items included the distribution, size, number, shape, intensity and enhancement of all lesions on head MRI. Results The typical MRI findings of these patients were as follow: 1) most lesions were located at periventricle area (62 cases, 75.61%) and the deep part of supratentorial white matter (55 cases, 67.07%); 2) there were over 10 lesions in 62 cases (75.61%); 3) the lesions were predominantly ≤ 1 cm (62 cases, 75.61%), and the next were > 5 cm (23 cases, 28.05%); 4) intensity and enhancement features presented T1WI iso ⁃ or hypo ⁃ intensity, T2WI hyperintensity, and proton density weighted image (PDWI) lesions intensity higher than water in the ventricle; the black hole appeared in various size and mostly with round or patchy shape; nodular enhancement was more often seen in lesions smaller than 1 cm and ring⁃like in middle size lesions; peripheral or irregular enhancement was popular for big lesions and arc ⁃ like for subcortical lesions. In the atypical MRI findings: 1) lesions were large [maximum diameter > 5 cm (23 cases, 28.05%)]; 2) lesion enhancement was remarkable and last longer; 3) brain stem lesions were more common (61 cases, 74.39%). Conclusion Multiple and small lesions at periventricle area or deep white matter are the typical MRI findings for MS. Deformation due to MS lesions, micro⁃ black hole at convex or line⁃shape black hole at periventricle, arc ⁃ like enhancement for juxtacortical lesions or enhancement beside the temporal horn are improtant in the diagnosis of MS. Big lesions with remarkable enhancement and prevalent in brain stem are the findings in Chinese MS patients which are different from American or European MS cases. DOI：10.3969/j.issn.1672-6731.2011.03.013