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ObjectiveMyelin oligodendrocyte glycoprotein-associated disorders (MOGADs) are a rare new neurological autoimmune disease with unclear pathogenesis. Since a linkage of the disease to the human leucocyte antigen (HLA) has not been shown, we here investigated whether MOGAD is associated with the HLA locus.MethodsHLA genotypes of 95 patients with MOGADs, assessed between 2016 and 2018 from three academic centres, were compared with 481 healthy Chinese Han individuals. Patients with MOGADs included 51 paediatric-onset and 44 adult-onset cases. All patients were seropositive for IgG targeting the myelin oligodendrocyte glycoprotein (MOG).ResultsPaediatric-onset MOGAD was associated with the DQB1*05:02–DRB1*16:02alleles (OR=2.43; OR=3.28) or haplotype (OR=2.84) of HLAclass II genes. The prevalence of these genotypes in patients with paediatric-onset MOGAD was significantly higher than healthy controls (padj=0.0154; padj=0.0221; padj=0.0331). By contrast, adult-onset MOGAD was not associated with any HLA genotype. Clinically, patients with the DQB1*05:02–DRB1*16:02haplotype exhibited significantly higher expanded disability status scale scores at onset (p=0.004) and were more likely to undergo a disease relapse (p=0.030). HLA–peptide binding prediction algorithms and computational docking analysis provided supporting evidence for the close relationship between the MOG peptide subunit and DQB1*05:02allele. In vitro results indicated that site-specific mutations of the predicted target sequence reduced the antigen–antibody binding, especially in the paediatric-onset group with DQB1*05:02allele.ConclusionsThis study demonstrates a possible association between specific HLAclass II alleles and paediatric-onset MOGAD, providing evidence for the conjecture that different aetiology and pathogenesis likely underlie paediatric-onset and adult-onset cases of MOGAD.

Background and objectiveAetiology and pathogenesis of anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis, the most common autoimmune encephalitis, is largely unknown. Since an association of the disease with the human leucocyte antigen (HLA) has not been shown so far, we here investigated whether anti-NMDAR encephalitis is associated with the HLA locus.MethodsHLA loci of 61 patients with anti-NMDAR encephalitis and 571 healthy controls from the Chinese Han population were genotyped and analysed for this study.ResultsOur results show that the DRB1*16:02allele is associated with anti-NMDAR encephalitis (OR 3.416, 95% CI 1.817 to 6.174, p=8.9×10−5, padj=0.021), with a higher allele frequency in patients (14.75%) than in controls (4.82%). This association was found to be independent of tumour formation. Besides disease susceptibility, DRB1*16:02is also related to the clinical outcome of patients during treatment, where patients with DRB1*16:02showed a lower therapeutic response to the treatment than patients with other HLA alleles (p=0.033). Bioinformatic analysis using HLA peptide-binding prediction algorithms and computational docking suggested a close relationship between the NR1 subunit of NMDAR and the DRB1*16:02.ConclusionsThis study for the first time demonstrates an association between specific HLA class II alleles and anti-NMDAR encephalitis, providing novel insights into the pathomechanism of the disease.

Many studies have demonstrated that serum gamma glutamyltransferase (GGT) within normal range might be an early marker of oxidative stress. However the role of GGT in neuromyelitis optica (NMO) and multiple sclerosis (MS) is unknown.

Multiple sclerosis (MS) is a chronic immune mediated demyelinating disease of the central nervous system that exhibits sexual dimorphism and may benefit from sex-specific treatment. To investigate a potential influence of sex on immunomodulatory therapeutic effects in patients with MS, we performed a comprehensive analysis of published studies examining sex differences in the effects of disease-modifying treatments (DMTs) for MS.

•Late-onset MOGAD are more likely to experience delayed diagnosis as well as longer and delayed therapeutic intervention.•Brain involvement may be modulated by comorbidities in the elderly MOGAD patients.•The comorbidities alter the clinical manifestations of late-onset MOGAD.

NMOSD develops primarily in women of childbearing age, and several previous studies have shown that the disorder may increase the risk of miscarriage. However, there are no reports, to our knowledge, of fetal malformation, other than neonatal hydrocephalus, related to NMOSD. We report a 30-year-old woman who experienced recurrent neuritis and who was seropositive for AQP4-IgG. She became pregnant, and the fetus was found to have ectrodactyly. Histological analysis of the placenta showed moderate inflammatory infiltration; however, whether fetal malformation in NMOSD is related to inflammation and AQP4-IgG remains to be determined.

The physical processes triggering the fluid flow within the stressed rock are highly complex and not fully understood. The granite sample obtained from Creighton mine, Canada, was subjected to the temperature-pressure effects using a special rock mechanic testing machine equipped with a high precision gas monitor. It is shown that when the sample approached to the peak stress during the uniaxial compression test, the connective cracks instantaneously occurred accompanied by a swarm of AE activities, which suddenly decrease the fluid pore pressure. This change can be able to drive the gas back to the newly emerging crack due to the formation of gas pressure gradient within the damage zones. It is indicated that the different permeabilities among the zones can dominate the suction-exhaust proceeding of pore fluids within rock mass. Beyond the volumetric strain at null, the deformation of the stressed rock leads to a reversely change in pore pressure of closed pores. The feature for the gas emission determined by the changes in pore structure of rock is also discussed and analyzed.

•The performance of five algorithms in early diagnosis of MS was compared.•Extreme Gradient Boosting (XGBoost) had a higher recall, specificity, and precision.•XGBoost showed the best performance in both training and test sets.•61%, 51%, and 49% of patients could be diagnosed with MS, 1, 2, and 3 years earlier.•Our model was effective to help reduce MS diagnostic delays.

lSex, age, ethnicity and pregnancy may be intrinsic risk factors for relapse.lRecent attack, MRI finding, AQP4-IgG positivity and GFAP level may predict relapse.lOld age, severe and frequent attack and myelitis may suggest worse prognosis.lMonoclonal antibody therapies may be safe and more effective for relapse prevention.lRelapse prediction may assist in choosing treatment in high-relapse risk patients.

•Teriflunomide 14 mg demonstrated long-term safety and efficacy up to 6.3 years in patients with RMS.•The incidence of adverse events was similar to the TOWER core study.•Disability progression and relapse activity remained low and stable over time.•These findings align with those in other teriflunomide extension studies.