BACKGROUND AND PURPOSE:Efgartigimod, a neonatal Fc receptor inhibitor, reduces IgG recycling and thus decreases pathogenic IgG autoantibody levels. This subpopulation analysis aimed to assess the efficacy, safety, and tolerability of subcutaneous efgartigimod PH20 in Chinese participants with chronic inflammatory demyelinating polyneuropathy (CIDP). METHODS:ADHERE was a multistage, randomised-withdrawal, placebo-controlled phase II trial in adult participants with active CIDP. Eligible participants received open-label treatment with efgartigimod weekly for ≤12 weeks (Stage A) and those with confirmed evidence of clinical improvement (ECI) were randomised to receive double-blind treatment with efgartigimod or placebo weekly for ≤48 weeks (Stage B). Primary endpoints were proportion of participants with confirmed ECI (Stage A) and time to clinical deterioration as measured by adjusted Inflammatory Neuropathy Cause and Treatment score (Stage B). This descriptive analysis reports the results from the Chinese subpopulation. RESULTS:ADHERE enrolled 58 participants from mainland China for Stage A and of those, 47 were randomised (21 efgartigimod, 26 placebo) for Stage B. In Stage A, 45 (77.6%; 95% confidence interval [CI], 64.7%-87.5%) participants achieved confirmed ECI. In Stage B, median time to clinical deterioration was not reached with efgartigimod vs. 113.0 days (95% CI, 43.0-181.0 days) with placebo (hazard ratio, 0.313; 95% CI, 0.109-0.905). Across stages, most adverse events were mild or moderate, and no death occurred. No adverse events led to treatment discontinuation. CONCLUSIONS:Subcutaneous efgartigimod PH20 demonstrated clinical response and lowered the risk of clinical deterioration compared to placebo in Chinese participants with CIDP, while maintaining favourable safety and tolerability profiles.

Myasthenia gravis (MG) is a T/B cell-driven autoimmune disease. The immunomodulatory mechanisms of the common immunosuppressant tacrolimus (TAC) on the immune repertoire are unclear. This study investigated TAC’s immunomodulatory effects via high-throughput sequencing of peripheral blood mononuclear cells from four MG patients pre- and post-four months of TAC monotherapy, revealing dynamic T-cell receptor (TCR) and B-cell receptor (BCR) repertoire remodeling. The immune repertoire of MG patients was characterized by a skewed usage of TRBV gene families compared to healthy controls, indicating an underlying immune dysfunction. Longitudinal analysis post-TAC therapy revealed potential downregulation of IGHV1-69 and IGHV3-43 gene frequencies (p < 0.05, FDR > 0.1), alongside non-significant trends toward shorter CDR3 lengths and reduced clonal diversity in both IGH and TRB (p > 0.05). The BCR repertoire underwent greater dynamic remodeling, while the TCR repertoire remained relatively stable, as evidenced by the persistence of dominant clones and overlapping TRB clones. BCR diversity and V or J gene usage in TCR and BCR showed potential associations with clinical severity. These data reveal skewed antigen recognition profiles in MG pathogenesis, with TAC orchestrating multimodal immunomodulation through peripheral immune repertoire reshaping.

Diseases associated with antibodies targeting nodal-paranodal cell-adhesion molecules have been recognized as a distinct entity termed autoimmune nodopathy (AN) since 2021. Efgartigimod, a neonatal Fc receptor antagonist, may interfere with the efficacy of monoclonal antibodies. Conventional pharmacokinetic principles suggest that complete elimination of drug interactions requires approximately five half-lives. However, whether this standard applies to FcRn antagonists remains unclear. We report a patient with anti-contactin-associated protein 1 (CASPR1) antibody-mediated AN refractory to intravenous immunoglobulin and plasma exchange. A novel sequential therapy was administered: rituximab was given after one efgartigimod half-life. During one-year follow-up, serum anti-CASPR1 IgG converted from 1:100 to negative, the INCAT score improved from 3/2 to 1/1, the MRC sum score increased from 48 to 54, and CD19+ B-cell count was 0.95/μl one month post-rituximab. B-cell depletion was sustained. This novel sequential strategy achieved sustained antibody reduction without compromising B-cell depletion, suggesting that the required washout period for FcRn antagonists prior to monoclonal antibody administration may be shorter than traditional pharmacokinetic models predict. It represents a feasible and promising therapeutic option for AN patients unresponsive to IVIG and PE, although further validation in larger cohorts is needed.

ABSTRACT Introduction Amyloid beta plaques and tau tangles are the primary hallmarks of Alzheimer's disease (AD). Recently, passive anti‐Aβ immunotherapy for AD has markedly advanced, as supported by evidence from AD animal models and clinical trials. Whereas innate immunity significantly contributes to AD pathology, it does not fully represent the immune mechanisms linked to this condition. Therefore, focus should be directed toward adaptive immunity, encompassing both humoral and cellular immunity. Methods Relevant publications and clinical trial data up to February 2026 were systematically reviewed to summarize the mechanisms, therapeutic targets, safety profiles, and translational applications of CD8+ T cells in AD. Results Clinical and animal studies have particularly suggested a potential involvement of T cells in AD pathogenesis. T cells that infiltrate the central nervous system (CNS) exert both protective and detrimental effects on neural tissue in AD. Because autoreactive CD8+ T cells are generally expected to have cytotoxic effects on CNS cells, they have received less attention. Nevertheless, accumulating evidence suggests that CD8+ Treg cells are involved in various diseases. Conclusion However, the function of anti‐Aβ‐specific CD8+ T cells in Alzheimer's disease (AD) remains ambiguous. Many subsets of CD8+ T cells have been well‐studied in autoimmunity. We suggest that CD8+ T cell subsets identified in AD studies may constitute a promising area for future AD research.

AIMS:To compare the real-world effectiveness, surgical and economic outcomes of preoperative rapid antibody clearance therapy (RACT: lymphoplasmapheresis (LPE), efgartigimod (EFG)) versus oral immunosuppressants (Oral IS) in generalized myasthenia gravis (gMG) patients undergoing thymectomy. METHODS:This retrospective study included 78 patients (36 Oral IS, 42 RACT: 25 LPE, 17 EFG). PRIMARY OUTCOME:3-month postoperative quantitative myasthenia gravis (QMG) score. SECONDARY OUTCOMES:1-month postoperative exacerbation rate, 3- and 6-month MG activities of daily living (MG-ADL), 6-month QMG, surgical outcomes (operative time, blood loss, postoperative myasthenic crisis (POMC)), perioperative costs (pre- and post-reimbursement). Propensity score overlap weighting balanced covariates. Sensitivity analyses used propensity matching; multiple imputation handled missing data. RESULTS:After weighting, 3-month QMG scores showed no significant difference between RACT and Oral IS groups (mean difference (MD) -0.23, 95% CI: -2.99 to 2.54, p = 0.831) nor between the EFG and LPE subgroups (MD 1.15, 95% CI: -3.97 to 6.26, p = 0.567); similar for MG-ADL. All groups improved over time (p < 0.001). For EFG vs. LPE, 1-month exacerbation rate was 43.3% vs. 26.1% (p = 0.412). No significant between-group differences between EFG and LPE were found in 6-month QMG/MG-ADL scores and surgical outcomes. EFG had higher preoperative pre-reimbursement costs (MD 14,500 CNY, p = 0.026), but no cost differences remained after insurance. Sensitivity analyses confirmed robustness of the primary findings. CONCLUSION:Preoperative RACT effectively reduced QMG in gMG patients, with no significant postoperative medium-term effectiveness and safety differences between RACT and Oral IS. Similarly, no significant differences in postoperative medium-term effectiveness, safety, or post-reimbursement costs were observed between EFG and LPE.

OBJECTIVE:Pompe disease is a rare, progressively debilitating lysosomal disorder. Enzyme replacement therapy (ERT) is an established treatment targeting the underlying enzyme deficiency. Alglucosidase alfa has shown benefits in survival, ambulation, and respiratory function and was approved in China for both infantile-onset (IOPD)and late-onset Pompe disease (LOPD) in 2015.To assess the effectiveness and safety of 52-week Alglucosidase alfa treatment among Chinese patients with LOPD in a multicenter, single arm, open-label, prospective clinical study. METHODS:Forty-one eligible LOPD patients received Alglucosidase alfa infusions at 20 mg/kg every 2 weeks for 52 weeks. Primary endpoints included the six-minute walk test (6MWT), percentage of predicted forced vital capacity (FVC), and safety profile. Secondary endpoints encompassed manual muscle test (MMT), maximal inspiratory and expiratory pressure (MIP and MEP), Quick motor function test (QMFT) scores, and health-related quality of life (SF-12). RESULTS:After 52 weeks, the mean 6MWT distance significantly improved by 43.6 m (P = 0.0017). Although the mean percentage of predicted FVC improved by 2.4%, the difference was not statistically significant (P = 0.1424). MIP and MEP percentages improved, reaching maximal improvement at 38 weeks. Both MMT and QMFT scores demonstrated significant improvements, with increases of 2.5 points (P < 0.0001) and 5.6 points (P < 0.0001), respectively. PCS significantly improved by 3.8 points (P = 0.0039), while MCS improvement was not statistically significant. A total of 32 participants (78.0%) experienced 137 treatment-emergent adverse events (TEAEs). Most of these TEAEs were mild to moderate in severity and resolved without sequelae. CONCLUSIONS:Alglucosidase alfa demonstrated a positive benefit-risk profile in Chinese LOPD patients, confirming its safety and effectiveness.

Tacrolimus (TAC) is recommended for the patients with drug tolerance or respond poorly to other conventional immunosuppressants in myasthenia gravis (MG), but its effectiveness is influenced by dose and genetic polymorphism. Studies suggest that HLA polymorphisms are significantly associated with susceptibility to MG, but the relationship between HLA and TAC efficacy in MG has not been explored. In this paper, we investigated the correlation between TAC therapeutic efficacy and HLA in different MG subgroups. HLA-C*03 was associated with a better response to TAC in patients with early-onset MG, generalized MG, and those with a high concentration of TAC. While HLA-A*11:01 showed poor responsiveness to TAC in generalized MG. Furthermore, computational docking was used to demonstrate the binding situation of HLA-A with the TAC binding protein FKBP1A. It showed that HLA-A*11:01 had a higher binding strength with FKBP1A than HLA-C*03, indicating that the combination of different types of HLA and FKBP1A may be one of the reasons affecting its therapeutic efficacy. This study highlights the influence of HLA on the efficacy of TAC among different MG subgroups, providing clues for precise treatment of MG with TAC.

Although CD20-directed B cell depletion has long been used in neuromyelitis optica spectrum disorder (NMOSD), high-quality, large-scale, randomized controlled trials remain limited. In this multicenter, randomized, double-blind phase 3 trial, we evaluated obinutuzumab β (MIL62), a novel glycoengineered type II anti-CD20 monoclonal antibody, in patients with NMOSD. Eligible participants aged 18-70 years with aquaporin-4-immunoglobulin G (AQP4-IgG)-seropositive NMOSD and an Expanded Disability Status Scale (EDSS) score of 7.0 or lower were randomly assigned (1:1) to receive intravenous obinutuzumab β 1,000 mg (n = 45) or placebo (n = 46). The primary outcome-time to first adjudicated relapse on or before week 52-was met: relapse occurred in two of 45 (4.4%) obinutuzumab β-treated participants and in 21 of 46 (45.7%) placebo-treated participants (hazard ratio = 0.069, 95% confidence interval: 0.016-0.296, P < 0.0001). The incidence of grade 3 or higher treatment-related adverse events was similar between the obinutuzumab β group (6.7%) and the placebo group (6.5%). These findings support obinutuzumab β as a glycoengineered type II anti-CD20 therapeutic option for patients with AQP4-IgG+ NMOSD. ClinicalTrials.gov identifier: NCT05314010 .

BACKGROUND:In the global Vivacity-MG3 study, nipocalimab (30-mg/kg loading dose; 15-mg/kg every-2-weeks) demonstrated sustained disease control versus placebo plus standard-of-care for generalized myasthenia gravis (gMG); this post-hoc analysis evaluated nipocalimab efficacy for participants with moderate-to-severe ocular symptoms (baseline score of ≥2 points on either ocular-domain item of MG-activities-of-daily-living [MG-ADL]). RESEARCH DESIGN AND METHODS:Mean MG-ADL and Quantitative Myasthenia Gravis total scores change-from-baseline (CFB) through Week (W)24 were assessed using ANCOVA. W24 percentages of participants with ≥2-point improvement in MG-ADL total (meaningful-within-person-improvement) or ocular-domain scores were compared using odds ratios (OR). Longitudinal odds of ≥2-point ocular-domain improvement were evaluated using generalized-estimating-equations logistic models. RESULTS:Nipocalimab (n = 54/77) and placebo-treated (n = 51/76) participants with moderate-to-severe ocular symptoms had similar baseline (mean [SD]) MG-ADL total (10.1 [2.8]; 9.4 [1.9]); ocular-domain scores were 4.1 (1.2); 3.5 (1.0). At W24, LS-mean (SE) CFB for nipocalimab versus placebo were -4.71 (0.50) versus -3.24 (0.50), p = 0.042 (MG-ADL total) and median (IQR) -2.00 (-3.0 to -0.5) versus -1.00 (-1.5 to 0.0), p = 0.024 (ocular-domain). W24 ≥ 2-point ocular-domain improvements were observed with nipocalimab (40.7%) versus placebo (19.6%; OR = 3.47 [95% CI = 1.34-8.97]; p = 0.010). Adverse events: 77.8% (nipocalimab) and 76.5% (placebo). CONCLUSION:These hypothesis-generating results suggest that nipocalimab may provide sustained disease control, reduce ocular symptoms, and improve activities-of-daily-living versus placebo in participants with gMG and moderate-to-severe ocular symptoms. CLINICAL TRIAL REGISTRATION:www.clinicaltrials.govidentifier is NCT04951622; www.clinicaltrialsregister.euidentifier is 2020-005732-29.

Exhausted T cells (Tex), characterized by impaired cytotoxic function, play a detrimental role in anti-tumor and anti-infection immunity but represent promising therapeutic targets for autoimmune diseases. Persistent exposure to auto-antigens drives autoreactive CD8+ or CD4+T cells toward an exhausted-state, thereby mitigating excessive damage to healthy tissues. Inducing T cell exhaustion may offer a targeted approach to suppress pathological autoimmunity. In this review, we describe the markers, characteristics, and developmental phases of T cell exhaustion, discuss its close association with autoimmune diseases, and highlight Tex as a potential biomarker. We also summarize Tex-targeted therapeutic strategies, including inhibitory receptor activation, TCR overstimulation, and metabolic intervention, to provide insights for future treatments. The clinical translation gap of Tex-targeted therapy has also been proposed from stability, safety, and disease-specific considerations. Although challenges remain in areas such as antigen specificity and tenuous tolerance, therapies targeting Tex hold considerable potential to disrupt pathogenic circuits, realize disease remission, and reduce the risk of relapse in autoimmune diseases.

Myo-inositol oxygenase (MIOX), as the sole enzyme catalyzing myo-inositol (MI) catabolism in mammals, plays a central role in maintaining intracellular MI homeostasis. Dysregulation of MIOX activity disrupts MI metabolic balance, leading to pathological processes including oxidative stress, inflammation, and ferroptosis, which subsequently induce multiple diseases such as metabolic syndrome, neurological disorders, tumors, and reproductive/developmental disorders. This article systematically reviews the structure and function of MIOX as well as the pathological consequences arising from its dysregulation. Although its pathological significance is increasingly recognized, the molecular mechanisms of MIOX in many diseases have not been fully elucidated, and targeted modulators of MIOX are lacking. Future research should focus on the in-depth elucidation of the pathogenic mechanisms of MIOX disorders and the development of MIOX modulators, thereby providing precise therapeutic strategies for related diseases.

Postmenopausal osteoporosis (PMOP) is a chronic systemic bone metabolism disorder. Promotion in the patterns of human bone marrow mesenchymal stem cells (hBMSCs) differentiation towards osteoblasts contributes to alleviating osteoporosis. Aucubin, a natural compound isolated from the well-known herbal medicine Eucommia, was previously shown to possess various pharmacological effects. However, its effects on hBMSCs of PMOP patients are unknown. The aim of this present research was to investigate the impact and underlying process of aucubin on cell proliferation and osteogenic differentiation in hBMSCs isolated from PMOP patients. The ability of aucubin to inhibit the ferroptosis induced by erastin in hBMSCs was detected; ROS production, ferrous ion levels, SOD, MDA, and GPX activities were tested by using commercial kits. Next, ALP staining, ARS staining, RT-qPCR, RNA-sequencing, and Western blot were applied for determining the mRNA and protein expression levels associated with the osteogenesis of hBMSCs. The study also explored the involvement of BMP2/Smads signalling in aucubin promoting the osteogenesis of hBMSCs and evaluated the effects of aucubin intervention on osteoporosis using an ovariectomised rat model. The results indicated that aucubin significantly inhibited ROS generation and oxidative stress induced by erastin and protected against ferroptosis in hBMSCs. Additionally, aucubin facilitated osteogenic differentiation of hBMSCs by activating the BMP2/SMADs pathway and attenuated the progression of osteoporosis in OVX rats, suggesting a potential therapeutic benefit for postmenopausal osteoporosis (PMOP).

[This corrects the article DOI: 10.1016/j.lanwpc.2023.100846.].

Abstract Background: Disease-modifying therapies have been approved for the treatment of relapsing multiple sclerosis (RMS). The present study aims to examine the safety of teriflunomide in Chinese patients with RMS. Methods: This non-randomized, multi-center, 24-week, prospective study enrolled RMS patients with variant (c.421C>A) or wild type ABCG2 who received once-daily oral teriflunomide 14 mg. The primary endpoint was the relationship between ABCG2 polymorphisms and teriflunomide exposure over 24 weeks. Safety was assessed over the 24-week treatment with teriflunomide. Results: Eighty-two patients were assigned to variant (n = 42) and wild type groups (n = 40), respectively. Geometric mean and geometric standard deviation (SD) of pre-dose concentration (variant, 54.9 [38.0] μg/mL; wild type, 49.1 [32.0] μg/mL) and area under plasma concentration-time curve over a dosing interval (AUCtau) (variant, 1731.3 [769.0] μg∙h/mL; wild type, 1564.5 [1053.0] μg∙h/mL) values at steady state were approximately similar between the two groups. Safety profile was similar and well tolerated across variant and wild type groups in terms of rates of treatment emergent adverse events (TEAE), treatment-related TEAE, grade ≥3 TEAE, and serious adverse events (AEs). No new specific safety concerns or deaths were reported in the study. Conclusion: ABCG2 polymorphisms did not affect the steady-state exposure of teriflunomide, suggesting a similar efficacy and safety profile between variant and wild type RMS patients. Registration: NCT04410965, https://clinicaltrials.gov.

We aimed to evaluate the association between rituximab (RTX) treatment duration and relapse risk, and explore clinical outcomes following treatment discontinuation in neuromyelitis optica spectrum disorder (NMOSD). We retrospectively collected data from rituximab-treated patients (>1-year follow-up after treatment initiation) with NMOSD at five major clinical centers in China between 2016 and 2023. The main outcome measures were changes in relapse risk based on the RTX treatment duration and clinical outcomes following relapse after RTX discontinuation. The Andersen–Gill model was used to analyze treatment duration-relapse risk associations. In total, 106 rituximab-treated patients were included (40 patients discontinued and 66 continued RTX). Longer RTX treatment significantly reduced relapse risk (hazard ratio [HR]=0.43, P < 0.001). Among 28 patients who discontinued RTX and were followed-up for >1 year after drug withdrawal, 53.6

INTRODUCTION:Chimeric antigen receptor T-cell (CAR-T) therapy, a revolutionary immunotherapy originally developed for hematologic malignancies, has recently gained attention for its potential in treating autoimmune diseases. Increasing evidence suggests that CAR-T cells can precisely target pathogenic immune populations, offering durable remission and immune homeostasis restoration in neuroimmunological disorders such as myasthenia gravis (MG), neuromyelitis optica spectrum disorder (NMOSD), and multiple sclerosis (MS). METHODS:Relevant publications and clinical trial data up to September 2025 were systematically reviewed to summarize the mechanisms, therapeutic targets, safety profiles, and translational applications of CAR-T therapy in autoimmune diseases of the nervous system. RESULTS:Preclinical and early clinical studies demonstrate that CD19- and BCMA-directed CAR-T therapies effectively deplete autoreactive B cells with significant symptom improvement and minimal cytokine release syndrome or neurotoxicity. Novel constructs such as chimeric autoantibody receptor (CAAR)-T and CAR-regulatory T (CAR-Treg) cells enhance specificity and immune tolerance. Innovations including allogeneic "off-the-shelf" CAR-T, in vivo CAR engineering, and CRISPR-based safety switches further optimize therapeutic potential and accessibility. CONCLUSION:CAR-T therapy represents a promising frontier for refractory neuroautoimmune diseases. By precisely modulating immune networks, it offers a pathway toward long-term remission and personalized immunotherapy in clinical neuroimmunology.