Weibin Liu

Expansion of circulating counterparts of follicular helper T cells in patients with myasthenia gravis.

Growing evidence has demonstrated that dysfunction of follicular helper T (TFH) cells results in an abnormal positive selection of autoreactive B cells, which contributes to the development of autoimmune diseases. This study reveals that the frequency of circulating counterparts of TFH cells in myasthenia gravis (MG) patients is significantly higher compared to healthy controls. Interestingly, the frequencies of circulating TFH cells were positively correlated with the levels of serum anti-AChR Ab in MG patients. Our data suggest the presence of overactivation and expansion of circulating counterparts of TFH cells in MG patients, which may contribute to the immunopathogenesis of MG.

Thymectomy is a beneficial therapy for patients with non-thymomatous ocular myasthenia gravis: a systematic review and meta-analysis.

Ocular myasthenia gravis, an autoimmune disease, is characterized by extraocular muscle weakness. Myasthenia gravis is closely associated with the functional status of the thymus gland. The efficacy of thymectomy for non-thymomatous ocular myasthenia gravis remains controversial. Here, we present the first systematic review and meta-analysis of studies assessing the outcome of thymectomy in patients with non-thymomatous ocular myasthenia gravis and found that the pooled rate of complete stable remission was 0.5074 with considerable heterogeneity. Furthermore, subgroup analysis showed that the efficacy of thymectomy differed according to geographical location. Furthermore, thymectomy outcomes are better in children than they are in adults. Thymectomy clearly represents an effective treatment for patients with non-thymomatous ocular myasthenia gravis. However, more multicenter, randomized, controlled clinical trials are now required to confirm these conclusions.

The HLA-B*4601-DRB1*0901 haplotype is positively correlated with juvenile ocular myasthenia gravis in a southern Chinese Han population

Myasthenia gravis (MG) is a sporadic disorder that has been increasingly linked to inherited genetic factors. Previous studies have demonstrated that human leukocyte antigen (HLA) plays an important role in the pathogenesis of MG. We determined the genotypes of the HLA-A, B, and DRB1 alleles in 257 southern Chinese Han MG patients using polymerase chain reaction sequence-based typing (PCR-SBT). The allele frequencies in the MG patients were compared to 292 healthy controls using the case–control method. HLA-A*0207, HLA-B*4601, HLA-DRB1*0403, HLA-DRB1*0901, and HLA-DRB1*1602 were more frequent in juvenile ocular MG patients than controls. HLA-DRB1*0701 was significantly reduced in the juvenile ocular MG group compared with controls. HLA-A*0207-B*4601, HLA-B*4601-DRB1*0403, HLA-B*4601-DRB1*0901, and HLA-B*4601-DRB1*1602 were found to be in strong linkage disequilibrium in juvenile ocular MG patients. Within the MG patients, there was a strong positive association between HLA-B*4601-DRB1*0901 and juvenile ocular MG patients, and the value of odds ratios (OR) decreased as the disease became more severe and the age of onset increased. We believe this could be the main heredity phenotype in juvenile ocular MG patients from southern China and may be a clinical marker to predict the severity of the disease.

Clinical outcome and predictive factors of postoperative myasthenic crisis in 173 thymomatous myasthenia gravis patients

ABSTRACT Purpose: Thymectomy is the first-line therapy for thymomatous myasthenia gravis patients. The aim of this study is to explore the clinical outcome and predictors of postoperative myasthenic crisis (POMC) in these patients. Method: Clinical data of 173 thymomatous myasthenia gravis patients undergoing thymectomy from January 2000 to March 2013 were, retrospectively reviewed. Variables potentially affecting the occurrence of POMC were evaluated using binary logistic regression analysis. The difference in survival was determined by the log-rank test. Result: Fifty-one patients experienced POMC. Univariate analysis revealed that events significantly associated with increased risk of POMC include symptom duration before operation >2.75months, preoperative bulbar symptoms, incomplete resection, operation time ≥122.5 min and advanced stages (stage III or IV). Multivariate logistic regression analysis showed that preoperative bulbar symptoms (OR = 3.207 [1.413–7.278]; P = 0.005) and incomplete resection (OR = 4.182 [1.332–13.135]; P = 0.014) were independent risk factors for POMC. Twenty-eight patients (16.9%) died during the follow-up. The log-rank test revealed survival for patients with POMC was significantly worse than that for patients without POMC (P = 0.042). Conclusion: The important risk factors for developing POMC in thymomatous myasthenia gravis patients include the preoperative bulbar symptoms and incomplete resection of thymoma. Moreover, the patients with POMC had a worse prognosis compared with patients without POMC. Our study highlights the need of appropriate preoperative management of thymomatous myasthenia gravis patients to prevent the occurrence of POMC.

Clinical Characteristics of Juvenile Myasthenia Gravis in Southern China

Objectives To describe the clinical profile, clinical outcomes and factors that may affect the outcome of juvenile myasthenia gravis (JMG) patients in southern China. Methods We reviewed information relating to JMG patients treated and evaluated at the First Affiliated Hospital, Sun Yat-sen University, between 1998 and 2015. The study involved 327 JMG patients who had been followed up for ≥1 year. Results Overall, 77.4% patients showed initial symptoms in the prepubertal period (<12 years). 306 patients showed only ocular symptoms at onset. By the final follow-up, 61 ocular myasthenia gravis (OMG) patients (61/306, 19.9%) had developed generalized myasthenia gravis (GMG). Anti-acetylcholine receptor antibodies (AChR-Ab) titer was an independent risk factor for generalization. Eleven patients (3.4%) experienced spontaneous remission, but four relapsed. Low-dose oral prednisone (0.25 mg/kg) was administered when symptoms did not significantly improve after pyridostigmine treatment. Immunosuppressants were administered when prednisone was unsatisfactory. Optimal outcome was achieved in 59.6% of patients. Specifically, 60 patients (18.3%) attained complete stable remission (CSR), 12 (3.7%) attained pharmaceutical remission (PR), and 123 (37.6%) attained minimal manifestation (MM). In total, 53 OMG patients (21.5%) attained CSR, a significantly higher proportion than among the GMG patients (8.6%, P = 0.009). Moreover, 67.2% of patients with duration <2 years showed significant clinical improvement compared with 46.3% of those with duration >2 years (P < 0.001). Thymectomy did not exhibit definite efficacy for JMG patients. Conclusion There was a low frequency of cases positive for AChR-Ab in the Chinese population. AChR-Ab titer was revealed as an independent risk factor for generalization. Low doses of prednisone could treat JMG effectively with few side effects.

Imbalance of two main circulating dendritic cell subsets in patients with myasthenia gravis

Although it is well documented that circulating dendritic cells (DCs) have specialized features during many kinds of physiological and pathological conditions, there are few reports about the features of DCs in the peripheral blood of myasthenia gravis (MG) patients. We investigated the quantitative and component features of DCs and their implications in MG. Peripheral blood samples from different kinds of MG patients were collected and their clinical characteristics were recorded. Using flow cytometry, we distinguished circulating DC subsets [plasmacytoid DCs (pDCs) and myeloid DCs (mDCs)] and enumerated their densities in peripheral blood. Absolute numbers of circulating pDCs were significantly decreased in naïve MG patients compared with healthy controls, resulting in a markedly lower ratio of the pDC to mDC percentage in total circulating DCs (pDCs/mDCs), suggesting an imbalance in the proportions of the two main circulating DC subsets. The clinical status of MG patients was improved after drug treatment, together with increased pDCs/mDCs. In a longitudinal follow-up, we observed that circulating mDCs were significantly reduced after 1 month of therapy with a corticosteroid and immunosuppressant, resulting in recovery of pDCs/mDCs. Although the exact meaning of the proportion change in circulating DC subsets is unknown, pDCs/mDCs might reflect the balance between the autoimmune response and immune tolerance of a patient. Moreover, changes in pDCs/mDCs during treatment might be a promising marker to predict the efficacy of a specific drug used for MG patients.

Developing an international consensus guidance for myasthenia gravis using RAND/UCLA appropriateness method

1Department of Neurology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, Guangdong, China. 2School of Pharmacy, Sun Yat-Sen University, Guangzhou 510275, Guangdong, China. 3School of Earth and Environmental Sciences, Queens College, City University of New York, NY 11367, USA. 4Guangdong Provincial Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, Guangzhou 510080, Guangdong, China.