Chongbo Zhao

Thymoma is the most common anterior mediastinal tumor, which is linked to the loss of self-tolerance and the presence of autoimmunity. Various interactions between thymoma and autoimmune diseases have been identified, including myasthenia gravis, systemic lupus erythematosus, pure red cell aplasia, and pemphigus. In this retrospective case series, we reported rare autoimmune disorders with different organ involvement associated with thymoma. These included ocular paraneoplastic pemphigus, neuromyelitis optica spectrum disorder, diffuse panbronchiolitis and myositis. Our series broadens the spectrum of autoimmune disorders with shared T cell-mediated and B cell-dependent pathogenesis, underscoring the recurrence or relapse of thymoma-associated autoimmunity. The recognition of rare autoimmune presentations charts future treatment decisions and multidisciplinary care.

Background: Highly active Generalised myasthenia gravis (gMG) represents a group of patients with substantial disability and recurrent, life-threatening exacerbations. The recent emergence of targeted biologics has created new therapeutic opportunities, yet the potential of dual targeting complement C5 and B-cell signaling, such as B cell activating factor (BAFF)/proliferation-inducing ligand (APRIL), has not been thoroughly explored in these patients. Objectives: To explore the efficacy and safety of combined therapies with eculizumab (C5 complement inhibitor) and telitacicept (BAFF/APRIL inhibitor) in acetylcholine receptor antibody (AChR-ab)+ gMG patients who had high disease activity. Design: Single-centre, prospective, observational case series. Methods: Patients with highly active gMG despite advanced immunotherapies were enrolled in a neuromuscular reference centre for treatment with eculizumab and telitacicept. The primary endpoint was the change in Myasthenia Gravis Activities of Daily Living (MG-ADL) score. Minimal Symptom Expression (MSE), Clinically Meaningful Improvement (CMI), oral corticosteroid dose, serum IgG, and the incidence of treatment-emergent adverse events (TEAEs) were assessed. Results: Among the 22 patients ultimately enrolled, 16 (72.7%) had a history of myasthenic crisis (MC). Previously administered immunomodulatory therapies included intravenous immunoglobulin (IVIG) (16/22, 72.7%), efgartigimod (14/22, 63.6%), and plasma exchange (PE) (13/22, 59.1%). At Week 12 after initiation of eculizumab and telitacicept, significant improvements were observed: the MG-ADL score decreased substantially from a baseline value of 8.0 (IQR 5.0–10.0) to 1.0 (IQR 0.0–2.8) (p < 0.001), with all participants achieving CMI and 54.5% (12/22, 95% CI 32.2–75.6) achieving MSE. Concurrently, the daily oral prednisone dose was significantly reduced by 33% (from 22.5 mg to 15.0 mg; p < 0.001), and serum IgG levels declined markedly from 11.86 g/L to 7.14 g/L (p < 0.001). Notably, no meningococcal infections or other serious adverse events were reported. Conclusion: In highly active AChR-ab+ gMG requiring rapid disease control, simultaneous targeting of complement C5 and B cell activating pathway achieved clinical improvement, corticosteroid sparing, and reduced serum IgG, with an acceptable short-term safety profile. These proof-of-concept findings require confirmation in controlled trials with a mono-targeting therapy regimen and longer follow-up.

To describe the clinical outcomes of transitioning from efgartigimod to tacrolimus in chronic inflammatory demyelinating polyneuropathy (CIDP) patients. Six patients who completed the ADHERE trial and maintained clinical stability during the open-label extension phase (≥30 weeks of weekly efgartigimod) were transitioned to oral tacrolimus following efgartigimod discontinuation and were followed at 3-month intervals for 12 months. Clinical effectiveness was assessed utilizing the Inflammatory Neuropathy Cause and Treatment (INCAT) disability scale, centile Inflammatory Rasch-built Overall Disability Scale (cI-RODS), Medical Research Council (MRC) sum score (0-60), grip strength, 3m-Timed Up and Go Test (TUG) as well as electrophysiological examination. Safety was evaluated by monitoring adverse events. Peripheral T and B lymphocytes, interleukins and immunoglobulin levels were measured at each visit, and tacrolimus trough levels were monitored during follow-up. Three of six patients completed 12-month follow-up and achieved clinical stability or improvement by month 12. Two discontinued within three months due to poor clinical response and regained improvement following transition back to intravenous immunoglobulin or efgartigimod. One expressed a preference for traditional Chinese medicine and was lost to follow-up. No severe adverse events were observed. Oral tacrolimus may be a potential maintenance approach for sustaining clinical stability in a subset of CIDP patients stabilized on efgartigimod. Longitudinal naive B-cell monitoring warrants further investigation as a potential early indicator of clinical instability during tacrolimus maintenance therapy.

Background: Generalized myasthenia gravis (gMG) is a rare, chronic autoimmune disorder that imposes a substantial disease burden in China. As novel therapeutic options emerge, understanding patient preferences has become essential for treatment decision-making. This study aimed to assess treatment preferences and willingness to pay (WTP) among Chinese gMG patients. Methods: This multicenter, cross-sectional survey was conducted from March to August 2025 among patients with gMG in China. A discrete choice experiment was used to quantify patient preferences by presenting hypothetical treatment scenarios defined by eight key attributes. A mixed Logit regression model was used to identify preference drivers, and WTP was estimated to reflect the monetary value assigned to changes in treatment attributes. Results: Among the 909 analyzed patients, the mean age was 48.9 ± 13.27 years, and 61.8% were female. Within the selected attribute sets, safety was a key determinant of patient preferences, with consistently favored for lower risks of adverse drug reactions (ADRs) on metabolic diseases, infection, myelosuppression, and liver and kidney function impairment; WTP increased as risk levels decreased. Patients preferred oral administration, followed by subcutaneous injection and intravenous infusion. Infrequent dosing, once every-6-month, weekly or daily, was preferred over 2–3 times daily. Faster onset time of action (≤2 weeks) was favored, and higher out-of-pocket costs were disfavored. Subgroup analyses revealed young patients valued once weekly dosing, subcutaneous injection, and low risk of liver and kidney function impairment than old patients. Patients with high disease burden showed similar preferences for low and moderate ADRs risk. High-income patients favored low ADRs risk, infrequent dosing, subcutaneous injection, and were less sensitive to cost than to low- and medium-income patients. Conclusion: This large-scale study was the first to investigated treatment preferences and WTP among Chinese patients with gMG. Within the selected attribute sets, patients prioritized safety, infrequent and convenient administration route, affordability, and rapid onset of action. Patients were willing to invest financially in therapies that align with these preferences. Incorporating patient preferences in clinical decision-making and reimbursement policy may improve adherence, reduce disease burden, and enhance quality of life for individuals with gMG in China.

Muscle health varies continuously from optimal function to severe pathology, yet no unified genetic framework quantifies this spectrum objectively. Here we develop MyoScore, a transcriptomic scoring system derived from transcriptome-wide association studies of 27 muscle-related phenotypes in over one million participants. TWAS selects genes whose genetically regulated expression in skeletal muscle associates with muscle-related traits, providing the genetic anchoring of the scoring system, while MyoScore itself is computed from measured bulk RNA-seq expression in new samples. From 1,116 transcriptome-wide association study (TWAS)-significant genes, 417 are expressed in skeletal muscle and form the basis of the scoring system. These genes are organized into five dimensions of muscle biology (Strength, Mass, LeanMuscle, Youth and Resilience), each scored from 0 to 100. Across 1,722 human skeletal muscle transcriptomes from four independent cohorts, MyoScore defines a continuous four-stage muscle health spectrum, discriminates healthy from diseased muscle (area under the curve 0.751–0.873), and correlates with histopathological severity, quantitative MRI and clinical outcomes. Functional validation through iPSC-to-myotube differentiation supports predicted expression changes for novel MyoScore genes. UK Biobank analysis of blood biomarker proxies in 467,123 participants demonstrates concordant associations with muscle phenotypes, and two-sample Mendelian randomization using skeletal muscle cis-eQTL supports causal directionality for 78% of gene-outcome pairs tested. Single-cell validation across 475,584 cells from two independent muscle ageing atlases shows that pseudobulk MyoScore declines with age, with type II myofibre nuclei most affected. Together, MyoScore establishes the first genetically anchored, dimension-resolved quantification of human muscle health, enabling objective assessment, patient stratification and biomarker discovery across the full spectrum from optimal function to severe disease.

Background: Predicting exacerbation risk in clinically treated patients with myasthenia gravis (MG) is essential for personalised intervention with neurotherapies. This study investigated whether dynamic monitoring of anti-acetylcholine receptor antibody (AChR-ab) levels could predict exacerbation in MG patients following minimal symptom expression (MSE), and developed a validated model for risk stratification to inform treatment decisions. Methods: We conducted a bicenter cohort study enrolling AChR-ab+ adult MG patients who achieved MSE. The derivation cohort included 339 patients from Huashan Hospital, and the validation cohort comprised 60 patients from West China Hospital. Exacerbation was defined as an increase of ≥ 2 points in the MG Activities of Daily Living score. Independent predictors were identified through univariate and multivariate logistic regression analyses, and a prediction model was subsequently developed and validated using discrimination and calibration metrics. Results: Longitudinal AChR-ab levels strongly correlated with disease progression, with a median time to exacerbation of 35.1 months post-MSE. Independent predictors included disease duration to MSE achievement, AChR-ab change, thymoma, comorbid immune-related diseases, and history of myasthenic crisis. The model demonstrated excellent discrimination in derivation (AUC = 0.886) and validation cohorts (AUC = 0.829), with good calibration in both datasets. Conclusion: Dynamic AChR-ab monitoring provides strong predictive value for MG exacerbation, and our validated prediction model offers clinicians a practical tool for personalized risk stratification and therapeutic decision-making in patients achieving disease stability.

Background: Optimal timing for treatment discontinuation in myasthenia gravis (MG) patients achieving minimal symptom expression (MSE) remains undefined. Methods: This prospective cohort study enrolled 196 MG patients from the Huashan MG Registry who achieved MSE and subsequently discontinued all treatments. Cox regression was used to identify prognostic factors for relapse. Among these, 20 patients experienced two discontinuation events and were analyzed separately for their second discontinuation. Results: Over a mean follow‐up of 111.10 months, 108 patients (55.1%) experienced relapse. Multivariate analysis identified four independent prognostic factors: onset age ≥ 50 years as a risk factor (HR 1.68, 95% CI 1.04–2.70, p = 0.032), and rituximab administration (HR 0.43, 95% CI 0.17–0.89, p = 0.015), treatment duration ≥ 14.3 months (HR 0.54, 95% CI 0.34–0.85, p = 0.008), and time from MSE to discontinuation ≥ 6.1 months (HR 0.51, 95% CI 0.32–0.83, p = 0.007) as protective factors. Infection, fatigue, and psychological stress were common relapse triggers. Conclusions: Complete treatment discontinuation after MSE in MG carries substantial relapse risk. Individualized discontinuation decisions incorporating younger onset age, prior rituximab use, adequate treatment and consolidation duration may optimize outcomes.

Background: Due to the rapid progression of the pneumonia in patients with Myasthenia gravis (MG), faster pathogen detection techniques are needed. The droplet digital polymerase chain reaction (ddPCR) has the ability to detect pathogens in about 3 h. Thus, this study focused on application of ddPCR in sputum samples in the MG patients with pneumonia and analyzed the association between ddPCR and other laboratory results. Methods: We prospectively enrolled 22 MG inpatients with pneumonia and collected 24 sputum samples. All samples were analyzed using traditional culture, ddPCR and metagenomic next-generation sequencing (mNGS) in parallel. Clinical outcomes during hospitalization were documented. Results: Among the 24 sputum samples collected from 22 MG patients, ddPCR achieved a 100% positivity rate with the identification of bacteria in all 24 samples, while mNGS also demonstrated a high detection rate, identifying bacteria in 23 of 24 samples (95.8%), and additionally detecting viral and fungal pathogens across multiple cases. In 4 patients with negative sputum culture results, pathogens were identified by both ddPCR and mNGS. Conclusion: The ddPCR demonstrated rapid and sensitive identification of predefined bacterial targets and drug-resistance genes, making it suitable for initial diagnostic screening and timely clinical decision-making in MG patients with pneumonia. The speed of ddPCR detection is faster than mNGS and traditional culture, and the results are similar to mNGS and culture, with good consistency.

Myasthenia gravis (MG) is an autoimmune neuromuscular disorder posing substantial disease burden in China, with significant impacts on patient quality of life. While conventional immunosuppressants remain fundamental therapy, biologic targeted agents — including B-cell targeting drugs, complement C5 inhibitors, FcRn antagonists, and IL-6R inhibitors — have brought major advances, especially for refractory and MuSK-antibody–positive MG. Increasing availability in China has demonstrated promising clinical outcomes, yet substantial barriers remain. Challenges include high drug costs, limited insurance access, insufficient multicenter clinical evidence, and disparities in physician adoption. China's research is improving, exemplified by local innovation with telitacicept and active participation in global trials, though most biologics remain imported. To maximize benefits, clinical application should be guided by antibody subtype and immunopathology, with individualized, dynamic regimens balancing efficacy, safety, and affordability. High-quality randomized trials, updated guidelines, broader insurance coverage, and R&D investment are urgently needed to promote individualized and accessible MG care in China.