Juvenile-onset myasthenia gravis (JOMG) is a unique clinical subtype in China, featured by a higher prevalence of ocular myasthenia gravis (OMG), higher seronegativity of acetylcholine receptor (AChR) antibodies, and better prognosis than that in adult-onset myasthenia gravis (AOMG). We previously identified low-affinity AChR antibodies in Chinese JOMG patients using cell-based assays (CBAs), indicating a predominantly AChR antibody-positive profile. Here, we further screened AChR antibodies in both Chinese AOMG and JOMG patients by CBAs. We recruited patients with MG who had not received prednisone or immunosuppressive therapies between June 2015 and June 2019, and divided them into AOMG and JOMG subgroups according to their ages at the time of recruitment. Clinical information and blood samples were collected. Serum AChR antibodies were detected by CBAs in HEK293T cells expressing clustered adult and fetal AChRs, as well as by enzyme-linked immunosorbent assays (ELISAs). Differences in AChR antibody profiles between AOMG and JOMG subgroups were determined. A total of 239 patients with MG were enrolled in the present study, including 121 AOMG and 118 JOMG patients. Based on ELISAs, 74.4% of AOMG (90/121) and 59.3% of JOMG (70/118) patients were anti-AChR positive (p = 0.02). However, CBAs yielded equal anti-AChR positivities (p = 0.64), as indicated by 80.2% of AOMG patients (97/121) and 77.1% of JOMG patients (91/118). Furthermore, among AOMG patients, 67.8% (82/121) were positive for both adult and fetal AChR antibodies, 5.8% (7/121) were positive for only adult AChR antibodies, and 6.6% (8/121) were positive for only fetal AChR antibodies, while these rates were 50.8% (60/118), 21.2% (25/118), and 5.1% (6/118), respectively, in JOMG cohorts (p < 0.01). Twenty-nine AOMG patients and 10 JOMG patients underwent IgG subclassification of AChR antibodies, which were all confirmed to be predominantly IgG1. The positive rates of AChR antibodies did not differ between Chinese AOMG and JOMG patients, as revealed by CBAs. Furthermore, the screened AChR antibodies were predominantly IgG1 in both AOMG and JOMG patients.

Patients in China with juvenile-onset myasthenia gravis present early, with a high prevalence of purely ocular symptoms, spontaneous remission rates, and low antibody seropositivity. Antibody detection using a cell-based assay has been reported to increase the diagnostic sensitivity in adult-onset myasthenia gravis. However, this method in patients with juvenile-onset myasthenia gravis has not been investigated. Patients with juvenile-onset myasthenia gravis who had not received prednisone or immunosuppressive therapy were recruited between June 2015 and April 2018 at the Huashan Hospital. Clinical information was collected. Serum anti-acetylcholine receptor antibodies were detected via cell-based assay with HEK293T cells expressing acetylcholine receptor subunits and rapsyn. Additionally, the IgG antibody subclass was identified. Eighty-two patients with juvenile-onset myasthenia gravis were enrolled in the current study. Among them, 48 patients were anti-acetylcholine receptor positive (58.5%) and 34 were seronegative (41.5%), as assessed via enzyme-linked immunosorbent assay. Cell-based assay yielded 63 positive subjects (76.8%) and 19 seronegative subjects (23.2%). All the enzyme-linked immunosorbent assay-positive samples showed robust immunofluorescence in the cell-based assay, whereas 15 of 34 enzyme-linked immunosorbent assay-negative patients (44.1%) were found to have low-affinity acetylcholine receptor antibodies. Among all the cell-based assay-positive patients, 41 were positive for both adult and fetal acetylcholine receptor antibodies (50.0%), 18 were found positive for only adult acetylcholine receptor antibodies (21.9%), and four were found to possess only fetal acetylcholine receptor antibodies (4.9%). Fifteen antibody-positive samples underwent subclassification and were confirmed to be IgG1 subclass predominant (n = 15, including eight adult and fetal acetylcholine receptor antibody positive, five only adult acetylcholine receptor antibody positive, and two only fetal acetylcholine receptor antibody positive). There were no significant differences in clinical features among patients with different antibody profiles. The cell-based assay showed increased sensitivity in acetylcholine receptor antibody detection in Chinese patients with juvenile-onset myasthenia gravis, and most cases of Chinese juvenile-onset myasthenia gravis are still acetylcholine receptor autoantibody mediated. Furthermore, the antibodies detected are predominately of the IgG1 subclass.

To compare HLA typing between juvenile- and adult-onset myasthenia gravis (MG), we enrolled 101 children (age ≤12 years) and 168 adults (age ≥20 years) with MG. We excluded patients with histories of thymoma, thyroid disease, or other autoimmune disease. We selected 41 seronegative juvenile-onset patients with ocular symptoms only, and 41 seropositive adult-onset patients with generalized symptoms. We used next-generation sequencing for typing and analysis of HLA genes (Loci: A, B, C, DPA1, DPB1, DQA1, DQB1 and DRB1). Haplotypes HLA-A∗02:07:01-B∗46:01:01-C∗01:02:01-DQA1∗01:01:01-DQB1∗03:03:02-DRB1∗09:01:02, HLA-A∗11:01:01, HLA-A∗24:02:01, and HLA-DPA1∗02:02:02 were found to be related to juvenile-onset MG and HLA-A∗01:01:01, HLA-A∗02:03:01, HLA-C∗03:04:01, and HLA-DQB1∗06:02:01 to adult-onset MG. Therefore, our findings suggested that HLA typing might determine the heterogeneity between AChR-Ab negative juvenile-onset and AChR-Ab positive adult-onset Chinese MG patients.

The objective of this study was to estimate mortality and survival in a large cohort of myasthenia gravis (MG) patients from Belgrade, Serbia, during the period 1979-2008. Data for all patients with MG were collected from hospital records and the Belgrade MG Registry. Within the 30-year study period, death occurred in 107 (20%) of 562 patients with MG, with MG-related fatality below 2%. The average MG mortality rate was 1.76 per 1,000,000 population (1.26/1,000,000 women, 2.45/1,000,000 men). A statistically significant increase was recorded for the average standardized mortality rate for all patients (P < 0.01). The mean survival from disease onset was 34.3 ± 2.0 years. Significantly shorter survival was observed in men compared with women and in patients older than 50 years compared with younger ones (P < 0.01). We observed long survival and low frequency of MG-related fatalities but increasing average standardized mortality rate, most notably in older men with MG. Muscle Nerve 58: 708-712, 2018.