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Objective: Myasthenia gravis (MG) is an autoimmune disorder that frequently affects females at reproductive age. Herein, we aimed to assess the associations of clinical factors with pregnancy-related outcome in MG.Methods: We searched PubMed and EMBASE for case-control and cohort studies that reported the MG status during or after pregnancy and relevant clinical variables. The data was extracted in proportions and odds ratios (ORs) with 95% confidence intervals (CIs) in subsequent meta-analysis.Results: Fifteen eligible articles reporting on 734 pregnancies with 193 worsening and 51 improved episodes were included out of 1765 records. The estimated worsening proportions in total, antepartum and postpartum periods were 0.36 (95% CI 0.25-0.40), 0.23 (95% CI 0.14-0.34) and 0.11 (95% CI 0.04-0.22) respectively. The proportion of pregnancy-related improvement in enrolled patients was 0.28 (95% CI 0.17-0.40), with 0.07 (95% CI 0.00-0.28) during pregnancy and 0.14 (95% CI 0.02-0.34) after pregnancy. No significant associations were disclosed between the clinical factors and MG worsening. Thymectomy before delivery is a strong predictor for MG improvement in postpartum period (OR 4.85, 95% CI 1.88-12.50, p = 0.001).Conclusion: The total proportion of pregnancy-related MG worsening and improvement in MG was 0.36 (95% CI 0.25-0.40) and 0.28 (95% CI 0.17-0.40), respectively. Thymectomy before the delivery may aid in clinical improvements associated with pregnancy. Future prospective cohort studies are required to determine more relevant factors. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor (CAR) based therapies have been adopted as an option for treating autoimmune diseases from the field of blood malignancies by targeting immune cells or rebalancing the pro-inflammatory milieu. Important questions still remained about the efficacy and safety regarding the dynamic and complex autoimmune pathological networks. We here reviewed the emerged developments in basic, translational, and clinical studies of the CAR based therapies in a wide spectrum of autoimmune diseases. The primary goal of the study is to provide some future perspectives on how to optimize the performance of CAR based therapies. The fundamental strategy is to engineer the recognition domains in CAR products for precisely targeting the components in the pro-inflammatory milieu. The second strategy is to incorporate multiple CARs in one carrier, or use fluorescein isothiocyanate (FITC)-CAR T cells for enhancing the therapeutic efficacy. In addition, we reviewed the preclinical evidence in disease-specific context. Overall, we aim to attract more attention in the field of developing future precision CAR based therapies to tailor medial decisions in autoimmune diseases. • CAR-based therapies eliminate self-reactive lymphocytes and/or rebalance the pro-inflammatory milieu. • Tailored recognition domains is critical for selecting precise targets regarding the heterogeneity of autoimmune disease. • Carrier cell types also play an important role in the performance of CAR-based therapies • Future optimized CAR-based therapies may have a role in precision therapies in treating autoimmune disease. [ABSTRACT FROM AUTHOR]

• Duration from onset to the crisis is significantly shorter in TMG patients. • The in-hospital clinical outcome of MC is worse in TMG patients compared with that in non-thymoma-associated MG patients. • MG patients with unresected thymoma had longer hospital stays than that with POMC. Thymoma-associated myasthenia gravis (TMG) had more severe symptoms and worse prognoses in comparison to non-thymoma-associated MG. Thymoma recurrence was frequently associated with transient worsening of MG and even acute respiratory failure, namely myasthenic crisis (MC). However, little is known about the clinical features and outcomes of MC in thymoma-associated MG patients. We performed a retrospective cohort study in MG patients recruited from 9 independent tertiary neuromuscular centers in China from Jan 2015, through Oct 2022. Overall, 156 MC from 149 MG patients with positive anti-acetylcholine receptor (AChR) antibodies were finally analyzed. Next, these patients were divided into two subgroups: the TMG group (n = 60 MCs, 58 patients) and the non-thymoma-associated MG group (n = 96 MCs, 91 patients). Compared with non-thymoma-associated MG, TMG patients had a significantly shorter disease duration from symptom onset to the crisis (17.95±40.9 vs 51.31±60.61 months, P <0.0001), a larger proportion of MGFA IVa as the initial onset clinical classification (6.67% vs 0, P = 0.0205), and a longer hospital stay (39.24±22.09 [6–111] vs. 33.2 ± 23.42 days [7–120]; P = 0.0317) during the crisis. Within the TMG group, the hospital stay was significantly longer in patients with unresected thymoma compared to that in postoperative myasthenic crisis (POMC) (47.68±24.9 [6–111] vs. 34.21±18.87 days [12–82]; P = 0.0257). Early identification of the MG categories may provide some hints in tailoring therapeutic strategies to improve the prognosis. [ABSTRACT FROM AUTHOR]

Background: Myasthenia gravis (MG) is the most prevalent autoimmune disorder affecting the neuromuscular junction. A rapid deterioration in respiratory muscle can lead to a myasthenic crisis (MC), which represents a life-threatening condition with high mortality in MG. Multiple CD4+ T subsets and hypercytokinemia have been identified in the peripheral pro-inflammatory milieu during the crisis. However, the pathogenesis is complicated due to the many types of cells involved, leaving the underlying mechanism largely unexplored. Methods: We conducted single-cell transcriptomic and immune repertoire sequencing on 33,577 peripheral blood mononuclear cells (PBMCs) from two acetylcholine receptor antibody-positive (AChR +) MG patients during MC and again three months post-MC. We followed the Scanpy workflow for quality control, dimension reduction, and clustering of the single-cell data. Subsequently, we annotated high-resolution cell types utilizing transfer-learning models derived from publicly available single-cell immune datasets. RNA velocity calculations from unspliced and spliced mRNAs were applied to infer cellular state progression. We analyzed cell communication and MG-relevant cytokines and chemokines to identify potential inflammation initiators. Results: We identified a unique subset of monocytes, termed monocytes 3 (FCGR3B+ monocytes), which exhibited significant differential expression of pro-inflammatory signaling pathways during and after the crisis. In line with the activated innate immune state indicated by MC, a high neutrophil–lymphocyte ratio (NLR) was confirmed in an additional 22 AChR + MC patients in subsequent hemogram analysis and was associated with MG-relevant clinical scores. Furthermore, oligoclonal expansions were identified in age-associated B cells exhibiting high autoimmune activity, and in CD4+ and CD8+ T cells demonstrating persistent T exhaustion. Conclusions: In summary, our integrated analysis of single-cell transcriptomics and TCR/BCR sequencing has underscored the role of innate immune activation which is associated with hypercytokinemia in MC. The identification of a specific monocyte cluster that dominates the peripheral immune profile may provide some hints into the etiology and pathology of MC. However, future functional studies are required to explore causality. [ABSTRACT FROM AUTHOR]

Background: Myasthenia gravis (MG) is an autoimmune disorder affecting neuromuscular junctions. Cytokines play important roles in facilitating the immune response and augmenting the pathogenic antibody production. The current study aims to sensitively characterize the serum levels of cytokines with very low concentration in generalized MG (gMG). Methods: Using ultrasensitive single-molecule arrays (SIMOA), we measured serum IL-2, IL-4, IL-5 and IL-12p70 in 228 participants including 152 immunotherapy-naïve anti-acetylcholine receptor (AChR) subtype gMG from Huashan MG registry and 76 age-matched healthy controls. Subgroup analysis was then performed by stratifying patients according to the onset ages, MGFA classification, disease duration at baseline. Results: Serum IL-2, IL-4, IL-5 and IL-12p70 levels were significantly elevated in gMG compared to controls (0.179 pg/mL versus 0.011 pg/mL, P < 0.0001; 0.029 pg/mL versus 0.018 pg/mL, P = 0.0259; 0.215 pg/mL versus 0.143 pg/mL, P = 0.0007; 0.132 pg/mL versus 0.118 pg/mL, P = 0.0401). Subgroup analysis revealed that IL-2 levels were slightly elevated in gMG with MGFA II compared to MGFA III/IV (0.195 pg/mL versus 0.160 pg/mL, P = 0.022), as well as elevated levels of IL-2 (0.220 pg/mL versus 0.159 pg/mL, P = 0.0002) and IL-5 (0.251 pg/mL versus 0.181 pg/mL, P = 0.004) in late-onset gMG compared with the early-onset gMG. gMG patients with a long duration had a significant increased serum IL-12p70 than those with a short duration (0.163 pg/mL versus 0.120 pg/mL, P = 0.011). Conclusion: Serum IL-2, IL-4, IL-5 and IL-12p70 levels were increased in AChR subtype gMG using ultrasensitive measurement. Serum cytokines with very low concentrations may provide as potential biomarkers in stratifying gMG patients in future prospective cohort studies. [ABSTRACT FROM AUTHOR]

The interrelationship between mental health and autoimmunity gains more and more attention in recent years. However, the causality between personality traits and autoimmune diseases remained largely unknown. We first conducted two-sample mendelian randomization (MR) analysis on the relationships between mood instability, which is a common personality trait in the general population, and 10 autoimmune diseases. The results were further validated in secondary analyses of sensitivity where different MR methods, ethnicities, genders, and ascertainment methods were compared. In the primary analyses, three autoimmune diseases showed genetical predisposition to mood instability: asthma (OR [95%CI] = 3.45 [2.48, 4.78], P = 1.33E- 13), hypothyroidism (OR [95%CI] = 1.02 [1.00, 1.03], P = 1.71E-02), and systemic lupus erythematosus (OR [95%CI] = 5.25 [1.21, 22.76], P = 2.67E-02). The results were consistent in subsequent secondary analyses. Three diseases remained significantly correlated with mood instability by different MR methods with asthma remaining significant in Finnish and mixed populations, and in females from the UK biobank, while hypothyroidism remained significant in both genders from the UK biobank. Mood instability is a modifiable risk factor for three autoimmune diseases including asthma, hypothyroidism and systemic lupus erythematosus. [ABSTRACT FROM AUTHOR]