Aberrant Dendritic Cell Subsets in Patients with Myasthenia Gravis and Related Clinical Features.

INTRODUCTION: Dendritic cells (DCs) play critical roles in the pathogenesis of myasthenia gravis (MG), and a series of DC-based experimental strategies for MG have recently been developed. However, the definite roles of different DC subsets in the mechanism of MG have scarcely been covered by previous studies. The present study aimed to investigate the levels of three main DC subsets, plasmacytoid DCs (pDCs) (CD303 positive) and two distinct subsets of conventional DCs (cDCs), namely CD1c+ cDCs and CD141+ cDCs, in MG patients and analyze related clinical features. METHODS: From January 2016 to December 2020, 160 newly diagnosed MG patients and matched healthy controls (n = 160) were included in the study, and their clinical data were collected. The blood samples from MG patients before treatment and controls were collected for flow cytometry analysis. A total of 14 MG thymoma, 24 control thymoma, and 3 thymic cysts were used to immunostain the DC subsets. RESULTS: The flow cytometry analysis showed a significantly higher frequency of circulating pDCs, CD1c+ cDCs, and CD141+ cDCs in MG patients than in healthy controls (p < 0.001 for all). Patients with early-onset MG (<50 years old) had a lower frequency of circulating pDCs but a higher frequency of circulating CD1c+ cDCs than those with late-onset MG (≥50 years old) (p = 0.014 and p = 0.025, respectively). The frequency of circulating pDCs was positively associated with the clinical severity of late-onset MG patients (r = 0.613, p < 0.001). 64.3% (9/14) of MG thymoma is of type B2 under the World Health Organization classification, which is higher than that in control thymoma (33.3%, 8/24) (p = 0.019). For type B2 thymoma, there were significantly more pDCs but fewer CD1c+ cDCs in MG thymoma than in the controls. CONCLUSION: The distribution of aberrant pDCs, CD1c+ cDCs, and CD141+ cDCs in MG patients displayed age- and thymoma-related differences, which may contribute to the impaired immune tolerance and lead to the onset of MG.

Fatigue, self-efficacy and psychiatric symptoms influence the quality of life in patients with myasthenia gravis in Tianjin, China.

BACKGROUND: Muscle weakness related to myasthenia gravis (MG) limits the daily functioning of patients. MG patients often experience subjective symptoms including psychiatric disorders, fatigue, and reduction in self-efficacy. All of which ultimately influence their life. The relationship between the subjective symptoms and health-related quality of life (HRQoL) has never been systematically explored among MG patients. OBJECTIVE: This study aimed to evaluate the HRQoL of patients with MG in China, and to assess the impact of potential predictors of HRQoL. METHODS: This was a cross-sectional observational study in patients with confirmed diagnosis of MG. Patients with MG were assessed using the 36-Item Short-Form Health Survey (SF-36) questionnaire, Self-Rating Depression Scale (SDS), Self-Rating Anxiety Scale (SAS), Fatigue Severity Scale (FSS), and Self-Efficacy for Managing Chronic Disease 6 items scale (SES6G). Disease severity was evaluated by two specialists at the same time. RESULTS: Patients had significantly lower mean SF-36 scores for the categories role physical and general health (GH). The mean physical and mental composite scores were 57.76 ± 21.28 and 60.03 ± 23.75. Sex and unemployment influenced the QoL. Financial burden was negatively associated with total SF-36 scores. Compared to the control group, patients with generalized symptoms (MGFA II and III) had lower SF-36 scores, but the patients with pure ocular symptoms (MGFA I) had not significant difference, except GH. The SF-36 scores were highly correlated with the severity of the disease, the states of mood, fatigue, and self-efficacy. CONCLUSIONS: The decrease in the HRQoL of patients with MG was related not only to the gender, severity of disease, and unemployment but also to the subjective experience including depressive and anxiety disorders, fatigue, and self-efficacy. In the course of treatment, the evaluation of HRQoL should be included in the routine assessment of patients with MG. Psychosocial treatment, social support, and health education should be advocated.

Chrysophanol Relieves Cognition Deficits and Neuronal Loss Through Inhibition of Inflammation in Diabetic Mice.

Patients with diabetes mellitus are easy to experience diabetic encephalopathy (DE) and other cognition dysfunction, whereas the neural alterations in developing this disease are unknown yet. Chrysophanol (CHR) is one of traditional Chinese medicine which was reported to show protective effects in cognition dysfunction and inflammatory in previously studies. In this current study, whether CHR protects learning and memory dysfunctions induced by diabetes disease or not and underlying mechanisms were studied. DE model was induced by streptozotocin (STZ, i.p.) in ICR mice. CHR was administrated 3 days after STZ treated mice which was confirmed with diabetes for consecutive 6 days. Learning and memory function was tested by Morris water maze after the CHR injection. The morphology of neuronal cells in hippocampus CA3 region was stained by HE-staining. ELISA and Western blot assay were used to determine the levels of pro-inflammation cytokines (IL-1ß, IL-4, IL-6, TNF-α) in hippocampus. Here, we demonstrated that mice harboring diabetes mellitus induced by STZ exhibit high blood glucose, learning and memory deficits detected by Morris water maze behavior tests. Application with CHR right after developing diabetes disease rescues partial blood sugar increasing, learning and memory deficits. The data also indicated that the death rate of neurons and the number of astrocytes in hippocampus CA3 region was significantly improved in diabetic mice. Moreover, the underlying mechanisms of CHR's protective effect are likely associated with anti-inflammation by downregulating the expression of pro-inflammation cytokines (IL-1ß, IL-4, IL-6, TNF-α) in hippocampus and inhibiting the over-activation of astrocytes in hippocampus CA3 region. Therefore, application with CHR contributes to the learning and memory deficits induced by diabetes disease via inhibitory expressions of inflammatory in hippocampus region.

Memory B cells in Guillain-Barré syndrome.

IgG autoantibodies against gangliosides show the highest titers at the disease onset of axonal Guillain-Barré syndrome (GBS), in which there are no IgM anti-ganglioside antibodies. We hypothesized that memory B cells take part in the development of producing IgG autoantibodies. In this study, we analyzed the memory B cells in patients with GBS using flow cytometry. There was significantly higher percentage of memory B cells in patients with GBS than the healthy controls. The Spearman correlation analysis demonstrated that increased percentage of memory B cells was positively correlated with the clinical severity of the patients with GBS. Our study provides the evidences that memory B cells may be involved in mechanism of GBS.

MicroRNA expression profiling in Guillain-Barré syndrome.

Guillain-Barré syndrome (GBS) is an acute inflammatory autoimmune disease affecting the peripheral nervous system. MicroRNAs (miRNAs) are a class of small noncoding RNAs that play critical roles in the process of various diseases. The miRNAs in GBS were less studied. In this study, using microarray technology, we found two miRNAs including has-miR-4717-5p and has-miR-642b-5p were upregulated in patients with GBS, which were further confirmed by PCR analysis. Kyoto Encyclopedia of Genes and Genomes pathway analysis suggested that the dysregulated miRNAs may be involved in the mechanism of GBS by affecting the cellular differentiation, cell survival and axonal outgrowth.

Increased plasmacytoid dendritic cells in Guillain-Barré syndrome.

Guillain-Barré syndrome (GBS) is a post-infectious autoimmune disease. Dendritic cells (DCs) can recognize the pathogen and modulate the host immune response. Exploring the role of DCs in GBS will help our understanding of the disease development. In this study, we aimed to analyze plasmacytoid and conventional DCs in peripheral blood of patients with GBS at different stages of the disease: acute phase as well as early and late recovery phases. There was a significant increase of plasmacytoid DCs in the acute phase (p=0.03 vs healthy donors). There was a positive correlation between percentage of plasmacytoid DCs and the clinical severity of patients with GBS (r=0.61, p<0.001). Quantitative polymerase chain reaction and flow cytometry confirmed the aberrant plasmacytoid DCs in GBS. Thus, plasmacytoid DCs may participate in the development of GBS.