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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.

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 SNPscanTM 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.