Clinical characteristics and therapeutic effect of myasthenia gravis coexisting with thyroid eye disease.

INTRODUCTION: Here, we describe the clinical characteristics and therapeutic effects of myasthenia gravis (MG) coexisting with thyroid eye disease (TED). METHODS: We collated clinical data from MG patients in our hospital between 2012 and 2022 and analyzed the clinical characteristics of MG patients with hyperthyroidism, MG patients with TED and ocular myasthenia gravis (OMG) patients with TED. RESULTS: We recruited 62 MG patients with hyperthyroidism, including 13 MG patients with TED and 10 OMG patients with TED. There were 70 MG patients without hyperthyroidism; 29 of these were OMG. Compared with patients without hyperthyroidism, patients with hyperthyroidism had an earlier age at onset and milder clinical symptoms (P < 0.05). The incidence of thymus hyperplasia in patients with hyperthyroidism and TED was significantly lower than that in patients without TED (38.5% vs. 69.4%, P < 0.05); these patients also had a significantly lower antibody titer for the acetylcholine receptor [0.72 (0.27, 14.93) nmol/L vs. 2.38 (0.28, 49.51) nmol/L, P < 0.05]. Diplopia was significantly more frequent in OMG patients with TED than in patients with OMG (84.6% vs. 44.8%, P < 0.05), and the rate of diplopia in OMG patients with TED was significantly higher after treatment with bromostigmine and glucocorticoid (69.2% vs. 3.4%, P < 0.05). CONCLUSIONS: MG patients with TED had a significantly lower incidence of thymus hyperplasia and a lower antibody titer for the acetylcholine receptor. Patients with OMG and TED are more likely to develop diplopia; it is very difficult to treat diplopia in these patients.

Transfer of patient's peripheral blood mononuclear cells (PBMCs) disrupts blood-brain barrier and induces anti-NMDAR encephalitis: a study of novel humanized PBMC mouse model.

BACKGROUND: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a severe autoimmune neuropsychiatric disease. Brain access of anti-NMDAR autoantibody through the blood-brain barrier (BBB) is essential for pathogenesis. Most previous animal models limit the investigation of etiologies of BBB damage in patients. METHODS: In this study, we established a novel humanized mouse model of anti-NMDAR encephalitis by intraperitoneal injection of patients' peripheral blood mononuclear cells (PBMCs) into BALB/c Rag2-/-Il2rg-/-SirpαNODFlk2-/- mice. RESULTS: We found that engraftment of patients' PBMCs not only produced potent anti-GluN1 autoantibodies, but also disrupted BBB integrity to allow brain access of autoantibodies, resulting in a hyperactive locomotor phenotype, anxiety- and depressive-like behaviors, cognitive deficits, as well as functional changes in corresponding brain regions. Transcriptome analysis suggested an exaggerated immune response and impaired neurotransmission in the mouse model and highlighted Il-1ß as a hub gene implicated in pathological changes. We further demonstrated that Il-1ß was produced by endothelial cells and disrupted BBB by repressing tight junction proteins. Treatment with Anakinra, an Il-1 receptor antagonist, ameliorated BBB damage and neuropsychiatric behaviors. CONCLUSIONS: Our study provided a novel and clinically more relevant humanized mouse model of anti-NMDAR encephalitis and revealed an intrinsic pathogenic property of the patient's lymphocytes.

Early autoimmunity and outcome in virus encephalitis: a retrospective study based on tissue-based assay.

To explore the autoimmune response and outcome in the central nervous system (CNS) at the onset of viral infection and correlation between autoantibodies and viruses. METHODS: A retrospective observational study was conducted in 121 patients (2016-2021) with a CNS viral infection confirmed via cerebrospinal fluid (CSF) next-generation sequencing (cohort A). Their clinical information was analysed and CSF samples were screened for autoantibodies against monkey cerebellum by tissue-based assay. In situ hybridisation was used to detect Epstein-Barr virus (EBV) in brain tissue of 8 patients with glial fibrillar acidic protein (GFAP)-IgG and nasopharyngeal carcinoma tissue of 2 patients with GFAP-IgG as control (cohort B). RESULTS: Among cohort A (male:female=79:42; median age: 42 (14-78) years old), 61 (50.4%) participants had detectable autoantibodies in CSF. Compared with other viruses, EBV increased the odds of having GFAP-IgG (OR 18.22, 95% CI 6.54 to 50.77, p<0.001). In cohort B, EBV was found in the brain tissue from two of eight (25.0%) patients with GFAP-IgG. Autoantibody-positive patients had a higher CSF protein level (median: 1126.00 (281.00-5352.00) vs 700.00 (76.70-2899.00), p<0.001), lower CSF chloride level (mean: 119.80±6.24 vs 122.84±5.26, p=0.005), lower ratios of CSF-glucose/serum-glucose (median: 0.50[0.13-0.94] vs 0.60[0.26-1.23], p=0.003), more meningitis (26/61 (42.6%) vs 12/60 (20.0%), p=0.007) and higher follow-up modified Rankin Scale scores (1 (0-6) vs 0 (0-3), p=0.037) compared with antibody-negative patients. A Kaplan-Meier analysis revealed that autoantibody-positive patients experienced significantly worse outcomes (p=0.031). CONCLUSIONS: Autoimmune responses are found at the onset of viral encephalitis. EBV in the CNS increases the risk for autoimmunity to GFAP.

Nomogram for the acute exacerbation of acetylcholine receptor antibody-positive generalized myasthenia gravis.

BACKGROUND AND OBJECTIVE: An acute exacerbation of myasthenia gravis (MG) can lead to the life-threatening myasthenia crisis which can increase the in-hospital mortality. This study aimed to clarify the correlative factor of the severity and activity of MG and the predictors of its exacerbation. METHODS: A prospective study was conducted to compare the clinical characteristics of acetylcholine receptor antibody (AChR-Ab)-positive generalized MG during acute exacerbation (AE) and in a stable state (SS). Logistic regression was used to determine risk factors, and a nomogram was developed. RESULTS: A total of 97 AChR-Ab MG patients were enrolled, of whom 44 had AE and 53 were in SS. The concentrations of AChR-Ab were 35.24 (23.26, 42.52) nmol/L and 19.51 (8.30, 36.93) nmol/L in the AE and SS groups (P = 0.005), respectively. The receiver operating characteristic curve showed that a single AChR-Ab predicted severity and acute exacerbation, with an area under the curve (AUC) of 0.679. Logistic regression analysis showed that, in addition to AChR-Ab (P = 0.018), bulbar symptoms (P = 0.001), interleukin (IL)-6 (P = 0.025), CD4+/CD8+ T cell ratio (P = 0.031), and CD19+ B cell proportion (P = 0.019) were independent risk factors for acute exacerbation of MG. The developed nomogram had an AUC of 0.878. The Hosmer and Lemeshow chi-square test was 4.37 (P = 0.929). CONCLUSION: AChR-Ab concentration was positively correlated with the severity and activity of MG. AChR-Ab concentration, alongside bulbar symptoms, IL-6 concentration, CD4+/CD8+ T cell ratio, and CD19+ B cell proportion can predict the acute exacerbation of MG.

Immunoadsorption with staphylococcal protein A column in autoimmune encephalitis.

BACKGROUND: Early treatment has a positive effect on autoimmune encephalitis. However, different treatments have individual differences and corresponding contraindications in the clinical. Few reports have described the application of immunoadsorption with Staphylococcal Protein A Column (SPA-IA) in neuroimmune diseases. We aimed to observe the safety and efficiency of SPA-IA in autoimmune encephalitis. PATIENTS AND METHODS: We retrospectively analyzed three cases of autoimmune encephalitis wherein the first-line treatment was ineffective or contraindicated. The clinical features and prognosis during and after SPA-IA are described in detail. RESULTS: All patients were definitely diagnosed with autoimmune encephalitis. After treated with SPA-IA, all antibody titers, except for the serum antibody titer in Patient 2, were markedly decreased in both the cerebral spinal fluid and serum. The mean fibrinogen levels before and after SPA-IA were stable, and there were no clinical bleeding events. The modified Rankin Scale scores and their symptoms improved significantly after the last SPA-IA session or 3 months later. CONCLUSIONS: SPA-IA may be a viable, efficacious, and safe treatment alternative for autoimmune encephalitis with contraindications to traditional treatment or poor response.

Thymomatous myasthenia gravis: 10-year experience of a single center.

OBJECTIVES: To summarize the clinical features of thymomatous myasthenia gravis (T-MG), examine the association between MG and thymoma, and identify the related factors or predictors for long-term prognosis of T-MG. METHODS: A retrospective, observational study was conducted on 100 patients with T-MG and 96 patients with non-T-MG (NT-MG) between January 1, 2009 and December 31, 2019. The baseline characteristics were recorded for each patient. Logistic regression was used to measure the association between all clinical variables and T-MG prognosis. RESULTS: Between the T-MG and NT-MG groups, age at onset (45.66 ± 11.53 years vs 39.06 ± 14.39 years); age >40 years (72.0% vs. 40.6%); AChR-Ab positive rate (100.0% vs. 83.3%); Myasthenia Gravis Foundation of America (MGFA) classification at the worst condition (≥grade III, 61.0% vs. 33.0%); thyroid dysfunction (7.0% vs. 20.8%); and outcome (complete stable remission + pharmacologic remission + improvement, 74.0% vs. 93.7%) were statistically significant (P < .05). Presence of thymoma (OR = 0.196, 95%CI = 0.076-0.511, P = .001) was a risk factor for MG. Male sex, post-operative complications, higher grade of MGFA classification, and thymoma Masaoka-Koga pathological stage were risk predictors for long-term prognosis of T-MG (P < .1). Use of preoperative anticholinesterase drugs (OR = 5.504, 95%CI = 1.424-21.284, P = .013) was identified as an independent predictor for T-MG. CONCLUSION: T-MG is clinically different from NT-MG, and thymoma is considered a risk factor for MG. Preoperative anticholinesterase drug use is a protective factor for long-term prognosis of T-MG. A comprehensive understanding of the characteristics of T-MG will likely help improve its prognosis.

AChRAb and MuSKAb double-seropositive myasthenia gravis: a distinct subtype?

INTRODUCTION: This study investigated the characteristics of double-seropositive myasthenia gravis (DSP-MG) in southern China for disease subtype classification. METHODS: A case-control study was carried out in which the characteristics of DSP-MG patients (n = 17) were compared to those of muscle-specific tyrosine kinase antibody-positive (MuSK)-MG and acetylcholine receptor antibody-positive (AChR)-MG patients (n = 8 and 27, respectively). We also performed a literature review of DSP-MG patients. RESULTS: Compared to AChR-MG, DSP-MG had greater bulbar dysfunction (47.1% vs 18.6%, P = 0.04), higher incidence of myasthenia crisis (41.2% vs 14.8%, P = 0.04), more severe Myasthenia Gravis Foundation of America classification at maximum worsening, greater autoantibody abnormalities (70.6% vs 33.3%, P = 0.015), greater need for immunosuppressant treatment (58.8% vs 3.7%, P < 0.001), and worse prognosis with less remission (11.8% vs 55.6%, P = 0.001). There were no differences between DSP-MG and MuSK-MG patients. DSP-MG described in published reports was comparable to MuSK-MG. DISCUSSION: DSP-MG in southern China may be a subtype of MuSK-MG.

Quantification of dendritic cell subsets in human thymus tissues of various ages.

BACKGROUND: Dendritic cells (DCs) in the thymus are involved in central tolerance formation, but they also have other functions in the thymus, such as pathogen recognition. The density changes of human thymic DCs have been hardly investigated. In this study, human thymus samples of various ages were collected for tissue sectioning and staining. The thymic cortex and medulla area as well as the densities of various subsets of thymic DCs were calculated. RESULTS: All common DC subsets were found in the human thymus of various ages. Most DCs had accumulated in the human thymic epithelial space, especially the medulla. We also found that the human thymic cortex had atrophied relatively faster than the medulla, which led to a gradual increase of the area ratio of the medulla to cortex with the increase of age. The densities of DC subsets in the human thymus showed various changes with increasing age, which contributed to the composition changes of DC subsets. The density of plasmacytoid DCs (pDCs) in the human thymus had increased gradually with aging, which suggested that pDCs plays another essential role in the thymus in addition to central tolerance. CONCLUSIONS: Inconsistent with the shrinking of the epithelial space in the thymus, the densities of DC subsets in the epithelial space of the thymus are maintained at a constant level with aging to preserve highly efficient autoreactive thymocyte screening. An increasing density of the thymic pDCs with aging implies an extra function of DCs in the thymus beyond central tolerance.

The metagenomic next-generation sequencing in diagnosing central nervous system angiostrongyliasis: a case report.

BACKGROUNDS: The incidence of angiostrongyliasis is increasing in recent decades due to the expanding endemic areas all over the world. Clinicians face tremendous challenge of diagnosing angiostrongyliasis because of the lack of awareness of the disease and less effective definitive laboratory tests. CASE PRESENTATION: A 27-year-old man initially manifested skin itching, emesis, myalgia and quadriparesis. With progressive weakness of four limbs and elevated protein in the cerebrospinal fluid (CSF), he was diagnosed as Guillain-Barré syndrome and treated with intravenous methylprednisolone and immunoglobulin. However, the patient deteriorated with hyperpyrexia, headache and then persistent coma. The routine tests for Angiostrongylus cantonensis (A. cantonensis) with both the CSF and the serum were all negative. In contrast, the metagenomic next-generation sequencing (mNGS) was applied with the serum sample and the CSF sample in the middle phase. The central nervous system (CNS) angiostrongyliasis was diagnosed by mNGS with the mid-phase CSF, but not the mid-phase serum. At the same time, the CSF analysis revealed eosinophils ratio up to 67%. The discovery of A. cantonensis was confirmed by PCR with CSF later. Unfortunately, the patient died of severe angiostrongyliasis. During his hospitalization, mNGS was carried out repeatedly after definitive diagnosis and targeted treatment. The DNA strictly map reads number of A. cantonensis detected by mNGS was positively correlated with the CSF opening pressure and clinical manifestations. CONCLUSIONS: The case of A. cantonensis infection highlights the benefit of mNGS as a target-free identification in disclosing the rare CNS angiostrongyliasis in the unusual season, while solid evidence from routine clinical testing was absent. The appropriate sample of mNGS should be chosen according to the life cycle of A. cantonensis. Besides, given the fact that the DNA reads number of A. cantonensis fluctuated with CSF opening pressure and clinical manifestations, whether mNGS could be applied as a marker of effectiveness of treatment is worth further exploration.

Hospital and healthcare insurance system record-based epidemiological study of myasthenia gravis in southern and northern China.

OBJECTIVE: This is the first cross-region epidemiological study of myasthenia gravis (MG) in China. We estimated the incidence, prevalence, and medical costs of MG in southern China and explored the differences between the southern and northern Chinese populations. METHODS: We collected and analyzed records from 20 hospitals in the southern city, Guangzhou, 13 hospitals in the northern city, Harbin, and two healthcare insurance systems: job based and residence based in Guangzhou during 2000-2017. RESULTS: (1) The estimated annual incidence of MG was 1.55-3.66 per 100,000, and the estimated prevalence of MG was 2.19-11.07 per 100,000 in southern China based on insurance records. (2) The proportion of hospitalized MG patients in the south-based hospital records was three times as high as that in the north-based hospital records. (3) Female MG prevalence was significantly higher than male MG prevalence in Guangzhou, while the similar gender difference in Harbin was not statistically significant due to higher variation in earlier years. (4) The average expense was $35-42 for each outpatient service and $2526-2673 for each hospitalization expense in the south. (5) Contrary to the increase of insurance-based estimate of MG prevalence, the proportion of hospitalized MG patients did not increase over the years, suggesting rising awareness and utilization of health insurance. CONCLUSIONS: The southern MG population had a significantly higher prevalence and a lower response threshold to medication than the northern MG population. These results are calling for further investigations on the genetic, cultural, and environmental variations of the Chinese MG populations between north and south.

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

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.

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.

Clinical Outcomes of Thymectomy in Myasthenia Gravis Patients with a History of Crisis.

BACKGROUND: The use of thymectomy in myasthenia gravis (MG) patients with a history of myasthenic crisis (MC) has not been well established. Here, we determined the efficacy of thymectomy by assessing the long-term clinical outcomes and reviewed thymectomy reports on MC patients. METHODS: Subjects included 31 patients who suffered at least one crisis before surgery, with a cumulative total 73 episodes of MC in Southern China between May 2000 and December 2010. Long-term follow-up was performed and clinical outcomes were evaluated. We used complete stable remission (CSR), termed an asymptomatic status without medication for at least 12 months; general complete remission (GCR), termed an asymptomatic status with or without some form of therapy excluding cholinesterase inhibitors, to assess patient outcomes. RESULTS: All patients underwent thymectomy with an overall complication rate of 16.1 % and a perioperative mortality rate of 3.2 %. Long-term follow-up occurred between 12.6 and 177 months, at which point 18 (58.1 %) patients experienced improved status, including one patient who achieved CSR; 13 (41.9 %) patients achieved GCR; 6 (19.4 %) showed unchanged status and one worse (3.2 %) status. The remaining 6 patients died, with 3 due to MG-related causes. Using a multivariate Cox regression analysis of GCR by characteristics, patients with better response to medical treatments before thymectomy were positively associated with GCR rates (p = 0.028). CONCLUSIONS: Extended transsternal thymectomy is a feasible and effective therapy for MG patients with crisis history, especially for those patients who have shown positive signs of remission after exhausting conventional medical treatments.

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 irradiation-associated myasthenia gravis exacerbation in thymomatous patients.

Exacerbations of myasthenia gravis (MG) in patients during radiotherapy for thymoma have never been adequately documented. This study aimed to identify potential risk factors for the occurrence of MG exacerbation during irradiation and to determine whether MG exacerbation during radiotherapy could affect the long-term clinical outcome of these patients. A total of 51 thymoma patients with MG receiving postoperative radiotherapy from January 2000 to March 2013 were retrospectively reviewed. Variables potentially affecting the occurrence of MG exacerbation were evaluated using Chi-square test or student's t test. The difference in the chance of achieving complete stable remission (CSR), pharmacologic remission (PR), and general remission (GR) in the patients with and without MG exacerbation was determined by the log-rank test. Fifteen patients deteriorated during the irradiation. Univariate analysis showed that the MG duration between MG onset and irradiation was significantly longer in patients with MG exacerbation than patients without it (p = 0.029). The ratio of patients with a history of myasthenic crisis and bulbar symptoms were also higher in patients with exacerbation of MG than patients without exacerbation of MG, although it did not reach statistic significant. The log-rank test revealed that patients without MG exacerbation had higher PR and GR rates (p = 0.017 and p = 0.009, respectively). The worsening of symptoms appears to be related to the longer MG duration and more severe MG before irradiation. Moreover, the patients with MG exacerbation had a worse prognosis compared with patients without MG exacerbation. Our study highlights the need for preventing the occurrence of MG exacerbation in these patients.

[Effects of thymectomy on bone age and height development in juvenile myasthenia gravis].

OBJECTIVE: To explore the effects of clinical indicators, particularly thymectomy on the development of juvenile myasthenia gravis (JMG) through the developmental status of bone age (BA) and height. METHODS: A cross-sectional study of 80 JMG patients was recruited to examine whether JMG patients had the abnormalities of height and bone development according to the distribution of height standard deviation score (Ht SDS) and BA. RESULTS: The mean BA was delayed by (0.15 ± 1.32) years compared with patient chronological age (CA). The mean Ht SDS (HtCA SDS -1.25 ± 1.03) was also lower than healthy controls. In multivariate analysis, the age at onset was negatively associated with delayed BA (P=0.007) whereas the cumulative intake of prednisone was negatively associated with HtCA SDS (P=0.043). No significant correlation existed between thymectomy and delayed BA or HtCA SDS. Delayed BA and slow growth existed in JMG patients. The age at onset of JMG was a correlative factor for delayed BA. And the intake of cumulative prednisone might be a determinant of height retardation. Thymectomy had no impact on the development of bone and height. CONCLUSION: We should pay more attention to monitoring BA and height in JMG patients to take appropriate therapeutic interventions.

[Characterization of muscular involvement in patients with Duchenne muscular dystrophy by magnetic resonance imaging].

OBJECTIVE: To study the order and degree of muscular affection in patients with Duchenne muscular dystrophy (DMD) during the course of disease. METHODS: Multiplex ligation dependent probe amplification (MLPA) was used to detect potential mutation of dystrophin gene. Magnetic resonance imaging (MRI) was used to scan the anteromedial aspect of thigh muscles. RESULTS: All of the 6 patients were found to have deletion or duplication mutations. The order of affection has been gluteus maximus, adductor magnus, quadriceps femoris, rectus femoris and biceps muscle of the thigh, while semimembranous muscle, semitendinosus, sartorius muscle and musculus gracilis are selectively affected and in a decreasing order. CONCLUSION: MRI can reflect the order, extent and degree of skeletal muscle involvement in patients with DMD, and can reflect pathological changes of damaged skeletal muscle at each stage, which may provide an important means for patient examination and diagnosis. No apparent correlation between the severity of disease and the nature of mutations was noted.

[Number of memory T cells in myasthenia gravis].

OBJECTIVE: To determine the altered number of memory T cells in myasthenia gravis (MG) patients and confirmed the existence of immune memory disorder. METHODS: A total of 27 MG cases (12 females, 15 males) undergoing expanded thymectomy at our hospital between 2009-2012. They were divided into 3 group of eutherapeutic (clinical relative score ≥ 50%), invalid (clinical relative score ≤ 25%) and improved (25% < clinical relative score <50%). Control group was composed of 17 cases of healthy subjects without immune system related disease. Flow cytometry was employed to detect the numbers of CD4⁺, CD8⁺, CD4⁺ CD45RO⁺, CD8⁺ CD45RO⁺, CD4⁺ CD45RO⁺ CCR7⁺, CD8⁺ CD45RO⁺ CCR7⁺, CD4⁺ CD45RO⁺ CD44(high) and CD8⁺ CD45RO⁺ CD44(high) T cells in PBMCs of 27 MG patients and 17 normal controls. RESULTS: As compared with healthy controls, the abnormal rates of CD4⁺ and CD8⁺ T cells were significantly higher in patients (P < 0.05), the number of CD4⁺ CD45RO⁺ CCR7⁺ T cells was significantly higher [(9.9 ± 5.5)% vs (6.6 ± 3.0)%, P = 0.012], the number of CD4⁺ CD45RO⁺ CD44(high) T cells was significantly higher [(6.8 ± 2.4)% vs (5.0 ± 3.0)%, P = 0.04] and the number of CD8⁺ CD45RO⁺ CCR7⁺ T cells was also significantly higher (P < 0.001). CONCLUSION: MG patients had immune disorders. And increased number of memory T cells and their activation may be pathogenesis of MG.

[Correlation study between ischemic stroke and polymorphism of human leucocyte antigen gene].

OBJECTIVE: To explore the correlation between ischemic stroke (IS) and the polymorphism of human leucocyte antigen (HLA) gene. METHODS: Antigen, allele, haplotype of HLA-A, B, C, DRB1, DQB1 in 94 IS patients and 503 healthy controls were detected by PCR-SBT. RESULTS: (1) There were 11 antigens, 17 alleles in HLA-A locus, 20 antigens, 34 alleles in HLA-B locus, 11 antigens, 16 alleles in HLA-C locus, 13 antigens, 26 alleles in HLA-DRB1 locus, 5 antigens, 13 alleles in HLA- DQB1 locus in IS group.(2) The allelic frequency of HLA-A*31: 01 (P = 0.016 9, RR = 2.827) , HLA-B* 37: 01 (P = 0.006 6, RR = 4.613) and HLA-DRB1*11: 06 (P = 0.000 2, RR = 37.981) in the IS patients was higher than that in healthy controls.(3) The haplotypic frequency of HLA-DRB1*11: 06-DQB1*03: 01 (P = 0.001, RR = 38.52) in the IS patients was higher than that in healthy controls. CONCLUSION: The susceptibility association of HLA-B*37: 01, HLA-DRB1*11: 06 and HLA-DRB1*11: 06-DQB1*03: 01 with IS and HLA gene play a genetic role in the occurrence of.