Increased serum interleukin-41 correlates with disease severity in myasthenia gravis.

BACKGROUND: Myasthenia gravis (MG) is an autoimmune disease mediated by pathogenic antibodies produced by abnormally activated B cells, resulting in neuromuscular junction transmission dysfunction. Interleukin-41 (IL-41) is a novel immunomodulatory cytokine that has been implicated in various metabolic, inflammatory, and autoimmune diseases. The role of IL-41 in MG is still unclear up to now, our study aimed to investigate the level of IL-41 in MG patients and its correlation with clinical features and inflammatory indicators. METHODS: Totally, 60 MG patients and 30 healthy controls (HC) were recruited. Baseline data and laboratory parameters were routinely recorded through electronic medical systems. IL-41 levels were measured by enzyme-linked immunosorbent assay. Proportions of T-cell and B-cell subsets and natural killer cells were analyzed by flow cytometry. The correlation between serum IL-41 and MG related parameters was investigated, and the clinical value of IL-41 in the diagnosis of MG was evaluated by receiver operator characteristic curve (ROC) analysis. RESULTS: Serum IL-41 levels in MG patients were higher than in HC, and were higher in Myasthenia Gravis Foundation of America (MGFA) III + IV group than that in MGFA I + II group. Serum IL-41 was positively correlated with MG-specific activities of daily living scale (MG-ADL), MGFA classification, platelet to lymphocyte ratio (PLR), and proportion of CD19+ B cells, while it was negatively correlated with high-sensitive C-reactive protein (hs-CRP) and circulatory plasma cells in MG patients. Serum IL-41 levels increased in patients who were treated with efgartigimod during the first cycle of therapy. However, compared to disease initiation, serum IL-41 levels decreased when clinical features steadily improved. ROC analysis showed that IL-41 had a diagnostic value for MG. CONCLUSION: The present findings suggested that serum IL-41 was increased in MG patients and was positively associated with the severity of the disease. IL-41 may be essential to the immunopathological mechanism of MG and a potential biomarker for MG.

Rescue treatment with add-on efgartigimod in a patient with impending myasthenic crisis: a case report.

Myasthenia gravis (MG) is an autoimmune disorder characterized by fluctuating muscle weakness. Severe patients may develop life-threatening respiratory failure and experience crisis. Plasma exchange or intravenous immunoglobulin (IVIg) is the first-line treatment option for myasthenia crisis, but some patients still poorly respond to them. Here, we first reported a generalized MG patient from China who was in a state of impending myasthenic crisis and did not respond effectively to IVIg but was successfully rescued by add-on efgartigimod. Especially, we also detected meaningful changes in T-cell and B-cell subsets after efgartigimod, promoting a potential role of efgartigimod in re-establishing immune homeostasis.

Macrophage migration inhibitory factor: A noval biomarker upregulates in myasthenia gravis and correlates with disease severity and relapse.

OBJECTIVE: To explore the relationship between macrophage migration inhibitory factor (MIF) and disease severity and relapse in patients with myasthenia gravis (MG). METHODS: 145 MG patients including 79 new-onset patients, 30 remission patients and 36 relapse patients were enrolled in this study. The detailed characteristics of all enrolled MG patients were routinely recorded, including gender, age, type, MGFA classification, antibody, thymic status, clinical score, treatment, MGFA-PIS and B cell subsets (memory B cells, plasmablast cells and plasma cells) detected by flow cytometry. Serum MIF levels were measured by enzyme-linked immunosorbent assay (ELISA) kit. The correlation of MIF levels with clinical subtypes, disease severity and B cell subsets were investigated. Moreover, logistic regression analysis was applied to assess the factors affecting relapse of generalized MG (GMG). RESULTS: Serum MIF levels were higher in new-onset MG patients than those in controls and were positively associated with QMG score, MGFA classification and memory B cells. Subgroup analysis revealed that MIF levels were increased in GMG patients than in ocular MG (OMG), as well as elevated in MGFA III/IV compared with MGFA I/II. With the remission of the disease, the expression of serum MIF decreased. The multivariate logistic regression models indicated that high MIF and thymoma was a risk factor for relapse of GMG, and rituximab could prevent disease relapse. CONCLUSIONS: MIF can be used as a novel biomarker to reflect disease severity and predict disease relapse in MG patients.

Circulating miRNAs drive personalized medicine based on subgroup classification in myasthenia gravis patients.

Myasthenia gravis (MG) is a classic autoimmune neuromuscular disease with strong clinical heterogeneity. The concept of subgroup classification was proposed to guide the precise treatment of MG. Subgroups based on serum antibodies and clinical features include ocular MG, early-onset MG with AchR antibodies, late-onset MG with AchR antibodies, thymoma-associated MG, MuSK-associated MG, LRP4-associated MG, and seronegative MG. However, reliable objective biomarkers are still needed to reflect the individualized response to therapy. MicroRNAs (miRNAs) are small non-coding RNA molecules which can specifically bind to target genes and regulate gene expression at the post-transcriptional level, and then influence celluar biological processes. MiRNAs play an important role in the pathogenesis of autoimmune diseases, including MG. Several studies on circulating miRNAs in MG have been reported. However, there is rare systematic review to summarize the differences of these miRNAs in different subgroups of MG. Here, we summarize the potential role of circulating miRNAs in different subgroups of MG to promote personalized medicine.

Plasma C18:0-ceramide is a novel potential biomarker for disease severity in myasthenia gravis.

Myasthenia gravis (MG) is an antibody-mediated autoimmune disorder characterized by fluctuation of fatigue and weakness of muscle. Due to the heterogeneity of the course of MG, available biomarkers for prognostic prediction are urgently needed. Ceramide (Cer) was reported to participate in immune regulation and many autoimmune diseases, but its effects on MG remain undefined. This study aimed to investigate the ceramides expression levels in MG patients and their potential as novel biomarkers of disease severity. Levels of plasma ceramides were determined by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Severity of disease was assessed by quantitative MG scores (QMGs), MG-specific activities of daily living scale (MG-ADLs) and 15-item MG quality of Life (MG-QOL15). The concentrations of serum interleukin-1ß (IL-1ß), IL-6, IL-17A, and IL-21 were determined by enzyme-linked immunosorbent assay (ELISA), and the proportions of circulating memory B cells and plasmablasts were detected by flow-cytometry assay. Four plasma ceramides levels we studied were detected higher in MG patients. And three of them (C16:0-Cer, C18:0-Cer, and C24:0-Cer) were positively associated with QMGs. In addition, receiver operating characteristic (ROC) analysis suggested that plasma ceramides have a good ability of differentiating MG from HCs. Importantly, only C18:0-Cer was shown to be positively associated with the concentration of serum IL and circulating memory B cells, and the decrease in plasma C18:0-Cer paralleled the clinical improvement of patients with MG. All together, our data suggest that ceramides may play an important role in the immunopathological mechanism of MG, and C18:0-Cer has the potential to be a novel biomarker for disease severity in MG.

The systemic inflammation markers as possible indices for predicting respiratory failure and outcome in patients with myasthenia gravis.

OBJECTIVE: This study aimed to explore the relationship between systemic inflammation markers and clinical activity, respiratory failure, and prognosis in patients with myasthenia gravis (MG). METHODS: One hundred and seventeen MG patients and 120 controls were enrolled in this study. Differences in the four immune-related markers of two groups based on blood cell counts: neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), lymphocyte to monocyte ratio (LMR), and systemic immune-inflammation index (SII) were measured. The stability of the associations between systemic inflammation markers and respiratory failure in MG patients was confirmed by adjusted logistic regression analysis. Moreover, Kaplan-Meier curve and multivariate COX regression models were applied to assess the factors affecting the outcome of MG. RESULTS: NLR, PLR, and SII were higher in MG patients than those in controls and were positively associated with MGFA classification, but not LMR. Adjusted logistic regression analysis showed that PLR was an independent predictor of MG with respiratory failure. The ROC curve demonstrated that PLR showed good sensitivity and specificity for the diagnosis of MG with respiratory failure. Kaplan-Meier curve showed that GMG, positive AchR-Ab, respiratory failure, high NLR, PLR, SII, and IVIg exposure correlated with the risk for poor outcomes in MG patients. The multivariate COX regression models indicated that GMG and high SII was a risk factor for poor outcome of MG. INTERPRETATION: The systemic inflammation markers expressed abnormally in MG patients, in which PLR may be an independent predictor of respiratory failure, and high SII and GMG were predictive risk factors for poor outcomes in MG patients.