Objective: Myasthenia gravis (MG) is an autoimmune disease caused by autoantibodies against neuromuscular junctions. Myasthenic crisis (MC) represents the most severe state of MG with high in‐hospital mortality. We aimed to identify immune signatures using in‐depth profiling in MC, and to assess the correlations between immune biomarkers with clinical severity longitudinally.Methods: We studied 181 participants including 57 healthy controls, 96 patients with MG who never experienced crisis and 28 MC patients from December 2018 through June 2020. Follow‐up visits occurred prospectively from crisis to 6 months off‐mechanical ventilation. The frequencies of 20 CD4⁺ T subpopulations and 18 serum cytokines were associated with clinical scores using correlations and principal component analysis.Results: Patients in crisis exhibited a proinflammatory CD4⁺T response with elevated Th1 (P = 0.026), and Th17 cells (P = 0.032); decreased T follicular helper 2 (Tfh2) cells (P < 0.001), Tnaive in Tfh cells (P < 0.001), ICOS⁻Tfh cells (P = 0.017), and T central memory in Tfh (P = 0.022) compared with controls, and increased frequencies of Tregs (P = 0.026) and Tfh17 (P = 0.045) compared with non‐crisis MG. Cytokine cascade was identified in crisis including the ones associated with Th1 (IL‐1β/2/12p70/18/27/IFN‐γ/TNF‐α), Th2 (IL‐4/5/13), Th17 (IL‐6/17A/21/22/23/GM‐CSF), Th9 (IL‐9), and Treg (IL‐10). Longitudinally, seven immune biomarkers including Tregs, IL‐2/4/17A/IFN‐γ/TNF‐α/GM‐CSF had significant correlations with MG‐activities of daily living score.Interpretation: Vigorous inflammatory CD4⁺ T signatures were identified in MC and are associated with clinical severity. Future research is needed to explore its potential candidacy for therapeutic intervention and predicting impending crisis.

Multiple sclerosis (MS) is a chronic inflammatory disease of the CNS characterized by demyelination and axonal damage. Experimental autoimmune encephalomyelitis (EAE) is a well-established animal model for human MS. Although Th17 cells are important for disease induction, Th2 cells are inhibitory in this process. In this article, we report the effect of a Th2 cell product, extracellular matrix protein 1 (ECM1), on the differentiation of Th17 cells and the development of EAE. Our results demonstrated that ECM1 administration from day 1 to day 7 following the EAE induction could ameliorate the Th17 cell responses and EAE development in vivo. Further study of the mechanism revealed that ECM1 could interact with αv integrin on dendritic cells and block the αv integrin–mediated activation of latent TGF-β, resulting in an inhibition of Th17 cell differentiation at an early stage of EAE induction. Furthermore, overexpression of ECM1 in vivo significantly inhibited the Th17 cell response and EAE induction in ECM1 transgenic mice. Overall, our work has identified a novel function of ECM1 in inhibiting Th17 cell differentiation in the EAE model, suggesting that ECM1 may have the potential to be used in clinical applications for understanding the pathogenesis of MS and its diagnosis.

Spinal and bulbar muscular atrophy (SBMA) is an X-linked recessive motor neuron disease characterized by slowly progressive weakness and atrophy of proximal limbs and bulbar muscles. To assess the genotype-phenotype correlation in Chinese patients, we identified 155 patients with SBMA and retrospectively examined available data from laboratory tests and neurophysiological analyses. Correlations between genotype and phenotype were analyzed. There was an inverse correlation between the length of CAG repeats and age at first muscle weakness (p<0.0001). The serum creatine kinase level showed a significant inverse correlation with disease duration and the age at examination (p=0.019 and p=0.004, respectively). Unlike previous classification of motor- and sensory-dominant phenotypes, all findings of nerve conduction, except the amplitudes of median nerve compound motor action potential, were positively correlated to the length of CAG repeats. A significant decline in sensory nerve action potential amplitudes may assist differential diagnosis of SBMA.