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ObjectiveThe homeostasis of the immune system is influenced by the gut microbiota. Previous studies have reported dysbiosis in the gut microbiota of myasthenia gravis (MG) patients. To investigate potential alterations in gut microbiota and metabolites in newly diagnosed and untreated MG patients, we conducted a case-control study.MethodsFecal samples were collected from 11 newly diagnosed and untreated MG patients as well as 11 age-and sex-matched healthy controls. These samples underwent analysis for gut microbiota using 16S ribosomal RNA (rRNA) gene sequencing, while fecal metabolome was analyzed using liquid chromatography-electrospray tandem mass spectrometry system (LC-ESI-MS/MS).ResultsThe microbial community richness (observed species) and diversity (Shannon and Simpson indices) were significantly lower in the MG group compared to the control group. Microbiota composition analysis revealed significant differences between the MG and control groups at phylum, family, and genus levels. Linear discriminant analysis effect size (LEfSe) analysis showed a substantial decrease in abundance of the genus Faecalibacterium within the MG group. Fecal metabolome analysis identified three up-regulated metabolites involved in amino acid metabolism (taurine, creatinine, L-carnitine), one up-regulated metabolite involved in lipid metabolism (oleic acid), with correlation analysis indicating a positive association between Faecalibacterium abundance and creatinine levels.ConclusionOur findings suggest that dysbiosis already exists in newly diagnosed and untreated MG patients, implying that dysbiosis within the gut microbiota may be an initiating factor contributing to MG pathogenesis. Furthermore, F. prausnitzii may hold promise as a probiotic for treating MG.

BackgroundVaccination remains the most effective measure to prevent SARS-CoV-2 infection and worse outcomes. However, many myasthenia gravis (MG) patients are hesitant to receive vaccine due to fear of worsening.MethodsMG patients were consecutively enrolled in two MG centers in North China. The “worsening” after vaccination was self-reported by MG patients, and severity was measured with a single simple question. The general characteristics and disease status immediately prior to the first dose were compared between the worsening and non-worsening groups. Independent factors associated with worsening were explored with multivariate regression analysis.ResultsOne hundred and seven patients were included. Eleven patients (10.3%) reported worsening after vaccination, including eight patients with mild or moderate worsening and three patients with severe worsening. Only one of them (0.9%) needed an escalation of immunosuppressive treatments. There were significant differences between the worsening and non-worsening groups in terms of Myasthenia Gravis Foundation of America classes immediately before the first dose and intervals since the last aggravation. Precipitating factors might contribute to the worsening in some patients. Logistic regression revealed that only interval since the last aggravation ≤6 months was associated with worsening after SARS-CoV-2 vaccination (P = 0.01, OR = 8.62, 95% CI: 1.93–38.46).ConclusionSARS-CoV-2 vaccines (an overwhelming majority were inactivated vaccines) were found safe in milder Chinese MG patients who finished two doses. Worsening after vaccination was more frequently seen in patients who were presumed as potentially unstable (intervals since last aggravation ≤6 months). However, mild worsening did occur in patients who were presumed to be stable. Precipitating factors should still be sought and treated for better outcome.

BackgroundThe absolute change in the severity score between the baseline and pre-specified time frame (absolute criterion) was recommended as a criterion for myasthenia gravis (MG) treatment response. But heterogeneity of disease severity might dilute major changes in individual patients. The rationality of relative criterion (improvement percentage) had not been evaluated in treatment response in patients with MG.ObjectivesTo investigate the consistency between an absolute criterion and a relative criterion in the evaluation of treatment response in patients with MG.MethodsWe retrospectively analyzed the treatment response to a 3-month standardized treatment protocol with only glucocorticoid in 257 MG patients native to immunological treatments. With the commonly used absolute criterion, cut-offs of relative criteria were generated with the receiver operating characteristic (ROC) curve in the whole cohort and in patients with different degrees of baseline severity stratified by pre-treatment quantitative myasthenia gravis score (QMGS). The consistency between absolute and relative criteria was examined with Cohen's Kappa test and Venn diagrams.ResultsThe absolute and relative criteria had an overall substantial consistency (Kappa value, 0.639, p < 0.001) in the cohort. The Kappa values were substantial to almost perfect in mild and moderate groups and moderate in severe groups between the absolute and relative criteria (all p ≤ 0.001). More patients were classified as responsive with an absolute criterion while as unresponsive with a relative criterion in the moderate and severe groups.ConclusionsThe overall consistency between absolute and relative criteria was substantial in the whole cohort. The inconsistency between the two criteria was mainly from the moderate or severe patients at the baseline.

IntroductionMinimal manifestation (MM) or better was recommended as the treatment goal for myasthenia gravis (MG). The sustainability of this status has not been described quantitatively in patients who had attained or are close to it.MethodsPatients who were with no or slight impact on daily living were recruited and followed at baseline and 3, 6, and 12 months. The included patients were classified into 3 post-intervention status (PIS) categories: remission (R), MM, and slight impact (SI). The proportion of patients belonging to real-time (not considering the intervals between assessments) and sustained (considering the intervals between assessments) PIS categories was compared at each follow-up. A sensitivity analysis (SA) cohort was established by including patients with PIS categories in all four follow-ups. The QMGS, MG-ADL, and MG-QOL15 scores in patients belonging to each PIS category at each follow-up were compared. The sustainability of the R/MM status was examined and correlated with real-time R/MM status at follow-ups.ResultsAt baseline, 376 patients could be classified, including 55 as R (14.2%), 209 as MM (54.0%), and 112 as SI (28.9%). In the whole cohort, 68.8–89.7%, 71–76.7% and 19.8–77.1% of the patients classified into real-time R, MM, and SI categories remained unchanged in each follow-up compared with the previous follow-up. The proportion of patients belonging to each real-time or sustained R/MM status at the three follow-ups was 89.7–92.1 or 60.8–67. In the SA cohort, at least 86.4% of the baseline R/MM patients remained in R/MM status till 12 months. There were no differences in keeping real-time R/MM status at 6 or 12 months between patients with and without sustained R/MM status at 3 and 6 months. There were differences in the QMGS, MG-ADL, and MG-QOL15 scores among patients belonging to each real-time category at baseline and follow-ups, ranking as R < MM < SI. The same trend was observed in patients belonging to each sustained PIS category with smaller scores than the same items of real-time categories.ConclusionThe sustainability of the R/MM status was confirmed. The R/MM status indicated a stable state of MG. The QMGS, MG-ADL, and MG-QOL15 scores may provide a quantitative reference for these PIS.

Myasthenia gravis (MG) is an autoimmune disease in which antibodies bind to acetylcholine receptors (AChR) or other functional molecules in the postsynaptic membrane at the neuromuscular junction. Vitamin D (VD) has a number of pluripotent effects, which include immune-regulation and bone metabolism. The immunomodulatory actions of 1,25(OH)2D3 are mediated by its binding to a vitamin D receptor (VDR). In the study, we undertook a case-control study to explore the association between VDR gene polymorphism and the susceptibility and severity of MG patients. Four hundred and eighty MG patients and 487 healthy controls were included and gene polymorphisms of VDR were determined with improved multiplex ligation detection reaction technique and SNPscanTM technique. MG patients were classified into subgroups by essential clinical features and by a comprehensive classification. The frequencies of alleles and genotypes were compared between the MG group and the control group, between each MG subgroup and the control group, and between each pair of MG subgroups. There were no significant differences in frequencies of alleles and genotypes between MG patients and healthy controls, between MG subgroups and healthy controls, or between each pair of MG subgroups in the analysis of subgroups classified by essential clinical features (onset age, gender, thymoma, AChRAb positivity, onset involvement) and the maximal severity (modified Oosterhuis score). In the analysis of subgroups with a comprehensive classification, the frequencies of alleles and genotypes in rs731236 showed significant differences between adult non-thymoma AChRAb negative MG subgroup and the control group, as well as the adult non-thymoma AChRAb positive MG group. In the Chinese Han population, rs731236 was found to be possibly associated with adult non-thymoma AChRAb negative MG patients, although this needs further confirmation.

Objective To explore the association of three single nucleotide polymorphisms (SNPs; rs228942, rs228941 and rs743777) in interleukin-2 receptor β subunit (IL-2Rβ) gene with the susceptibility and severity of myasthenia gravis (MG). Methods There were 480 MG patients and 487 normal controls enrolled in this study, and their three SNPs (rs228942, rs228941 and rs743777) in IL - 2Rβ gene were evaluated through SNPscanTM technique. Subgroups were classified by gender, age of onset, anti - acetylcholine receptor antibodies (AChR-Ab), thymus status, maximal involvement after 2 years of onset and maximal Oosterhuis score. Frequencies of alleles and genotypes were compared between MG group and control group, between MG subgroups and control group, and among subgroups under codominant, log - additive and overdominant models. Results The frequency of T allele of rs228942 in MG group was significantly higher than that in control group (χ2 = 4.692, P = 0.030, OR = 1.242, 95%CI: 1.021-1.511). There was significant difference in the frequency of rs228942 genotype between MG group and control group under log-additive model (P = 0.036, OR = 1.230, 95%CI: 1.010-1.480). The rs278942/rs228941 GT haplotype frequency in MG group was higher than that in control group (χ2 = 4.286, P = 0.038), while GG haplotype frequency in MG group was lower than that in control group ( χ2 = 5.333, P = 0.021). The frequencies of T allele of rs228942 was significantly higher in MG subgroups of onset age 15-50 years (χ2 = 7.474, P = 0.006, OR = 1.380, 95%CI: 1.095-1.740), non-thymoma (χ2 = 4.700, P = 0.030, OR = 1.261, 95%CI: 1.022-1.555) and maximal generalized involvement ( χ2 = 4.715, P = 0.030, OR = 1.287, 95% CI:1.025-1.617) than those in control group. Multivariate forward Logistic regression analysis found that onset age 15-50 years (OR = 9.026, 95%CI: 4.225-19.284; P = 0.000), onset age > 50 years (OR = 9.956, 95%CI:4.475-22.149; P = 0.000), thymoma (OR = 2.578, 95%CI: 1.393-4.773; P = 0.003) and positive AChR-Ab (OR = 1.946, 95%CI: 1.179-3.214; P = 0.009) were the independent risk factors for maximal involvement, while genotypes were not. Conclusions The rs228942 polymorphisms of IL-2Rβ gene may be associated with the susceptibility of MG, but not with the severity of MG. The rs228941 and rs743777 polymorphisms were not found to be associated with the susceptibility and severity of MG. DOI: 10.3969/j.issn.1672-6731.2016.10.006

Interleukin-4 (IL-4) is a potent growth and differentiation factor for B cells which play a vital role in the pathogenesis of myasthenia gravis (MG). IL-4 exerts its function by binding to three types of IL-4 receptor (IL-4R) complexes. IL-4Rα is the key component of the IL-4R complex. We hypothesize that polymorphism of IL-4Rα gene may be associated with the susceptibility and severity of MG. A Chinese cohort of 480 MG patients and 487 healthy controls were recruited. Polymorphisms of IL-4Rα gene were determined with SNPscan™ methods and compared between MG and control groups, as well as among MG subgroups. Rs2107356 and rs1805010 were found to be associated with adult thymoma associated MG, and rs1801275 was found to be associated with adult non-thymoma AChR-Ab positive MG. We did not found association between IL-4Rα polymorphism and the severity of MG. Genetic variations of IL-4Rα were found associated with the susceptibility of MG in Chinese Han population.