OBJECTIVES:Anti-adenylate kinase 5 (AK5) encephalitis is a rare, predominantly limbic autoimmune disorder featuring subacute cognitive and psychiatric decline. Given the limited literature and MRI's suboptimal sensitivity to neuroinflammation, often precluding timely therapeutic escalation, we sought to delineate the clinical and multimodal imaging spectrum of this condition and propose stage-specific management protocols. METHODS:Two female patients (aged 15 and 65 years) with subacute cognitive and psychiatric-behavioral disturbances were prospectively evaluated with serial MMSE, CASE and mRS clinical assessments at symptom onset and follow-up. All patients received intravenous methylprednisolone and immunoglobulin, with rituximab administered in one of the cases. Serum and CSF were tested for anti-AK5 antibodies using CBA and TBA. Brain MRI and 18F-DPA714 PET/MRI were performed to assess structural and microglial activation and aggregation patterns. RESULTS:Both patients exhibited prominent anterograde amnesia, psychiatric manifestations, and sleep disturbances. Anti-AK5 antibodies were detected in the serum of both patients via CBA at titers of 1:100 and 1:30, respectively. MRI demonstrated bilateral hippocampal/temporal lobe atrophy with mild T2/FLAIR hyperintensities. 18F-DPA714 PET/MRI revealed increased tracer uptake in the brainstem, frontal, occipital, and hippocampal regions. After intravenous methylprednisolone and immunoglobulin, with rituximab, the adolescent patient showed marked clinical and cognitive recovery (MMSE: 18 to 28; CASE: 6 to 0 in one year). Conversely, the older patient demonstrated limited improvement, with persistent amnesia and neuropsychiatric symptoms. CONCLUSIONS:This case series defines the clinical spectrum of anti-AK5 encephalitis, supporting 18F-DPA714 PET/MRI for detecting neuroinflammation correlating with clinical manifestations. Adjunctive CD20-targeted therapy showed efficacy in one patient, warranting B-cell immunotherapy research in larger cohorts.

Comprehensive profiling of peripheral blood may reveal candidate markers and therapeutic targets for anti-AChR antibody positive myasthenia gravis (MG) patients. We enrolled 37 anti-AChR antibody positive MG patients and 37 healthy controls (HCs), and blood immune cells were analyzed by mass cytometry, plasma proteins were determined by Cytokine Array, and metabolites were measured by targeted metabolomics. Compared with HCs, anti-AChR antibody positive MG patients showed increased classical monocytes and Th2-like cells, and decreased Th1-like cells, regulatory T cells, CD4+T, and CD28+T cells. Cytokine profiling revealed reduced retinol-binding protein 4 (RBP4), epithelial neutrophil-activating peptide 78 (ENA-78), and stem cell factor receptor (SCF-R), but elevated angiogenin, RANTES (CCL5), and cystatin-A. Metabolomics indicated lower dehydroepiandrosterone sulfate (DHEAS), cystine, and arginine, with higher lactate, sarcosine, and ornithine. Notably, glucocorticoid pretreatment reduced myeloid dendritic cells, Th2-like cells, dendritic cells, classical monocytes, and total monocytes. Integrated multi-omics analysis identified immune-metabolic interactions associated with anti-AChR antibody positive MG pathogenesis. This study highlights potential candidate markers and provides insights for targeted therapy.

Conventional magnetic resonance imaging (MRI) has limitations in detecting abnormalities in autoimmune encephalitis (AIE). This retrospective study evaluated the utility of 18F-DPA714 PET, a potential neuroinflammation biomarker, in MRI-negative AIE patients. 60 MRI-negative possible AIE patients (mean age 31.68 ± 11.05 years; 60

Background:Patients with rheumatic diseases are at high risk for latent tuberculosis infection (LTBI) reactivation. We aimed to evaluate whether a modified 3-month regimen (3HP-PUMCH) was non-inferior to the standard 9-month isoniazid regimen (9H) for tuberculosis preventive treatment in this vulnerable population. Methods:We conducted a multicenter, open-label, randomized, non-inferiority trial at nine tertiary general hospitals in China. Eligible participants were adults (18-70 years) with high-risk rheumatic diseases and LTBI undergoing immunosuppressive therapy. Patients were randomized (1:1) to receive either the 3HP-PUMCH regimen (twice-weekly rifapentine 450 mg plus daily isoniazid 300 mg) or the 9H regimen (daily isoniazid 300 mg). The primary endpoint was the occurrence of tuberculosis, with a non-inferiority margin of 1.4 percentage points. Analysis used the modified intention-to-treat population. The trial was registered with Chinese Clinical Trial Registry ChiCTR1800018242. Findings:Between 19 September 2018 and 18 August 2021, 536 patients with rheumatic diseases were enrolled. The cumulative rate of tuberculosis was 0.00% (0 of 249, 95% CI 0.00-1.47) in the 3HP-PUMCH group, compared with 1.15% (3 of 260, 95% CI 0.24-3.34) in the 9H group, with a rate difference of -1.15 percentage points (95% CI -2.4 to 0.14). Drug discontinuation rates due to serious adverse events or tuberculosis occurrence were 2.8% (7 of 249) in the 3HP-PUMCH group and 1.9% (5 of 260) in the 9H group (p = 0.509). Adverse drug reactions occurred in 24 (9.6%) of 249 patients versus 39 (15.0%) of 260 (p = 0.066), with hepatotoxicity in 11 (4.4%) of 249 versus 27 (10.4%) of 260 (p = 0.010). 223 (89.6%) of 249 patients completed treatment in the 3HP-PUMCH and 237 (91.2%) of 260 in the 9H group (p = 0.54). Interpretation:The short-course 3HP-PUMCH regimen was non-inferior to the 9H regimen in preventing tuberculosis and demonstrated a favorable safety profile, with high treatment completion in LTBI patients with rheumatic diseases. This regimen might be more suitable for patients with underlying diseases and those on concomitant medications. Funding:National Natural Science Foundation of China.

Objective To summarize the clinical characteristics of pseudodystonia, analyze its types that mimic dystonia, pathophysiological mechanisms, etiology, treatment and prognosis. Methods and Results The clinical characteristics of 7 pseudodystonia patients diagnosed and treated at Ruijin Hospital, Shanghai Jiaotong University School of Medicine from January to December 2023 were analyzed. Two cases had stiff limb syndrome, one case of autoimmune encephalitis, neuromyotonia, myotonic dystrophy type 1, abducens nerve palsy and palmar fascia contracture. Clinical manifestations included the posture abnormalities in 6 cases and repetitive movement in one case. Electrophysiological showed increased muscular spontaneous motor unit potentials in 2 cases, myokymic discharge accompanied by neuromyotonic discharge, and myopathic damage with myotonic discharge in one case each. Mimic foot dystonia and hand dystonia was observed in 2 cases, paroxysmal dystonia, hand dystonia combined with foot dystonia, and spasmodic torticollis in one case each. Pathophysiological classification included 5 cases of movement pathway disorders, and one case each of compensatory posture, skeletal, ligament, or joint diseases. After treatment, all 7 patients had a favorable prognosis. Conclusions Patients with pseudodystonia show involuntary postures and pattern movements tomimic dystonia, which can be characterized by acute attack, severe pain, no change in posture, persistent symptoms, and no sensory tricks. Most of the patients are treatable diseases, and early identification and treatment can achieve a good outcome.

Background:Creutzfeldt-Jakob disease (CJD) is a fatal neurodegenerative disorder caused by prion proteins, with microglial activation being a key immunopathological feature. This case report demonstrates the application of 18F-DPA-714 positron emission tomography (PET)/MRI, a second-generation translocator protein ligand, to visualise microglial activation in vivo in a patient with sporadic CJD (sCJD). Case presentation:A 57-year-old woman presented with progressive rapid cognitive decline and behavioural change. MRI revealed restricted diffusion within the patchy cortical ribbon of bilateral frontal, parietal, occipital lobes and right caput nuclei caudate. Lumbar puncture revealed positive 14-3-3 protein and robustly positive real-time quaking-induced conversion assay, fulfilling the diagnostic criteria for definite sCJD. 18F-DPA-714 PET/MRI showed extensive tracer uptake in bilateral cortical regions, caudate nuclei and the thalamus, indicating widespread microglial activation. The extent of abnormality on PET exceeded that seen on initial MRI, suggesting higher sensitivity for early pathological changes. Conclusions:This is the first reported case of sCJD evaluated with 18F-DPA-714 PET/MRI. The findings suggest that 18F-DPA-714 PET/MRI may provide complementary sensitivity beyond structural MRI, potentially improving early diagnostic confidence in sCJD.

Autoimmune encephalitis (AE) is an increasingly recognized inflammatory disorder of the central nervous system associated with autoantibodies against intracellular and surface membrane autoantigens. However, longitudinal studies for describing changes about diagnosis, therapeutic approaches, and economic burden of AE in China remain limited. We conducted a retrospective multi-center study, including 436 patients with definite AE diagnosed between January 2015 and December 2024 across five tertiary medical centers in eastern China. Evolution of demographic characteristics, diagnostic approaches, immunotherapies, clinical outcomes, and inpatient costs were systematically reviewed. The annual number of diagnosed AE cases increased steadily over the past decade, accompanied by a diversification of AE subtypes. Anti-NMDAR and anti-LGI1 encephalitis remained the most common forms, while cases with novel antibodies and antibody-negative AE increased notably after 2019, paralleling expanded antibody testing and PET imaging. Median diagnostic delay decreased significantly from 87 days in 2015 to 22 days in 2024. The use of second-line treatment rose substantially, reaching 46.4

Patients with rheumatic diseases (RDs) have a high risk of latent tuberculosis infection (LTBI) reactivation. However, research on tuberculosis preventive treatment (TPT) in this specific patient group remains limited. Additionally, the safety of the WHO - recommended 3 - month regimen of weekly rifapentine (RFT) plus isoniazid (INH) (3HP) has raised concerns among the Chinese population. This study aims to evaluate the efficacy, safety, and treatment completion of a modified 3HP regimen to a 9 - month INH monotherapy regimen in this vulnerable population.Flowchart of study participant intervention and follow-up. We conducted a multicenter, open-label, randomized noninferiority trial comparing a modified 3-month regimens of twice weekly RFT at 450mg plus daily INH at a maximum dose of 300mg (3HP-PUMCH) versus 9-month daily isoniazid at a maximum dose of 300mg (9H) in patients with RDs. Subjects were enrolled from 9 tertiary hospitals across China and followed for 2 years. The primary endpoint was confirmed active TB (ATB), with a noninferiority margin of 1.4%. A total of 536 patients with RDs were enrolled. In the modified intention-to-treat analysis, no cases of ATB occurred among 249 RDs patients in the 3HP-PUMCH group, with a cumulative rate of 0.00% (95% confidence interval [CI] 0.00 - 1.47), while 3 cases were observed among 260 patients in the 9H group, with a cumulative rate of 1.15% (95% CI 0.24 - 3.34), and the rate difference was -1.15% (95% CI -2.4 - 0.14). Rates of drug discontinuation due to serious adverse events or the occurrence of ATB in the 3HP-PUMCH group and the 9H group were 2.8% and 1.9% respectively (p=0.509), rates of investigator-assessed preventive drugs-related adverse reactions were 9.6% and 15.0% respectively (p = 0.066), with the rates of hepatotoxicity related to preventive drugs were 4.4% and 10.4% respectively (p = 0.010). Treatment completion rates were 89.6% in the 3HP-PUMCH group and 91.2% in the 9H group (p=0.542). The 3HP-PUMCH was as effective as the 9H in preventing ATB and demonstrated a favorable safety profile and high completion in LTBI patients with high-risk RDs. Moreover, this novel TPT regimen might be more suitable for patients with underlying diseases and those on concomitant medications, potentially offering a more practical and manageable option in complex clinical scenarios. All Authors: No reported disclosures

Abstract Background Anti-IgLON5 disease, a rare autoimmune neurological disorder, remains understudied in Eastern populations. This study aimed to characterize the clinical characteristics, treatment responses, and long-term outcomes of Chinese patients with anti-IgLON5 disease in a multicenter Chinese cohort. Methods This retrospective multicenter study enrolled 24 patients with anti-IgLON5 disease confirmed by serum and/or cerebrospinal fluid antibody testing from 17 centers in China. Human leukocyte antigen (HLA) typing was performed on patient blood samples. Clinical characteristics, mRS/ICS outcomes, treatment response, relapse, and long-term outcomes were analyzed. Short-term response was defined as improvement in mRS from admission to discharge, and relapse was defined as recurrence or worsening of symptoms after initial clinical improvement. Results The mean age at onset was 59.6 years. Among 18 patients who received immunotherapy, 10/18 (55.6%) met the definition of achieving a short-term response. Responders included more women (6/10 vs. 2/8), fewer patients with bulbar symptoms (4/10 vs. 5/8), and more frequently had HLA-DRB1*10:01 or HLA-DQB1*05:01 (8/10 vs. 4/8) compared with non-responders. Men aged ≥ 65 years had poorer outcomes, whereas younger men and most women responded well. Long-term follow-up was performed on 16 patients (median 18 months, range 3–60 months), and eight withdrew from follow-up. Relapse occurred in 4/16 patients (25.0%). It typically occurred about 6–12 months after discharge, often following abrupt treatment withdrawal, and was effectively controlled with re-treatment. Kaplan–Meier analysis indicated that relapse risk was the highest within the first 6 months post-discharge. Early treatment (≤ 6 months) tended to be associated with more favorable outcomes. Overall, 10/14 immunotherapy-treated patients with long-term follow-up (71.4%) showed improvement, and 7/14 (50.0%) became asymptomatic. In this cohort, HLA-DQA1*01:05 and HLA-DRB1*10:01/HLA-DQB1*05:01 were over-represented among the typed patients, and the response rate to immunotherapy was numerically higher than that in the Western population (55.6% vs. 40%). The misdiagnosis rate was 33.3%. The median diagnostic delay was 2 months (IQR, 1–12 months; range, 2 days–6 years). Conclusions As the largest cohort of anti-IgLON5 disease in China to date, this multicenter series demonstrated that Chinese and Western patients with anti-IgLON5 disease have both shared and distinct clinical characteristics. Chinese patients exhibited relatively favorable responses to early immunotherapy, relapse susceptibility requiring prolonged treatment, and potential HLA associations, offering new insight into disease management.

A 49-year-old male with Glial Fibrillary Acidic Protein Astrocytopathy (GFAP-A) presented with progressive cognitive decline, visual hallucinations, and bowel/bladder incontinence. Brain MRI revealed extensive white matter hyperintensities on T2-FLAIR sequences. After suboptimal response to first-line treatments including corticosteroids and intravenous immunoglobulin (IVIg), the patient was initiated on Ofatumumab (OFA) therapy. Treatment response was systematically monitored through validated clinical assessment tools (MMSE, MoCA, mRS, and CASE) and advanced neuroimaging, including conventional MRI and 18F-DPA714 PET. Following OFA treatment, the patient demonstrated marked clinical improvement and radiological resolution. Notably, 18F-DPA714 PET imaging captured dynamic changes in neuroinflammation and revealed distinct patterns not apparent on conventional MRI. This case demonstrates the potential effect on disease activity and safety of OFA in GFAP-A treatment while highlighting the value of 18F-DPA714 PET as an innovative tool for monitoring neuroinflammation and therapeutic response. To our knowledge, this represents the first comprehensive multimodal assessment using 18F-DPA714 PET/MRI in a GFAP-A patient treated with ofatumumab.

Background:Anti-MDA5 dermatomyositis is often complicated by interstitial lung disease and early mortality. Peripheral lymphopenia has been linked to poor outcomes, but the routinely measured lymphocyte compartments underlying this signal remain incompletely defined. We used hierarchical flow-cytometric immunophenotyping to characterize the mortality-associated lymphopenic pattern. Methods:In this exploratory retrospective cohort, we studied 64 adults with anti-MDA5 dermatomyositis who had baseline lymphocyte subset testing and 180-day follow-up. We compared major lymphocyte populations and T-cell differentiation subsets between survivors and non-survivors. Associations with mortality were assessed using ROC, Kaplan-Meier, and Cox regression analyses. Results:Thirteen of 64 patients died by day 180. Non-survivors showed T-cell-dominant lymphopenia, most marked in CD4+ central and effector memory T cells. Median-split Kaplan-Meier analysis showed lower 180-day survival with lower CD4+ memory T-cell counts (log-rank P = 0.00058). Each 1-SD increase in CD4+ memory T-cell count was associated with lower mortality after age adjustment (aHR 0.16, 95% CI 0.04-0.63, P = 0.008). CD4+ memory T-cell count had an AUC of 0.80 (95% CI 0.68-0.91), comparable to total CD4+ T-cell count (AUC 0.78, 95% CI 0.65-0.90). Findings were similar after separate adjustment for LDH or KL-6 and among patients with baseline RP-ILD. Conclusions:Reduced peripheral CD4+ memory T-cell counts characterized a T-cell-dominant immunophenotype associated with 180-day mortality in anti-MDA5 dermatomyositis. These exploratory findings refine the established CD4+ lymphopenia signal and require validation in independent cohorts.

To evaluate the effectiveness and safety of rituximab (RTX) compared to cyclophosphamide (CYC) in inducing remission with ANCA-associated vasculitis (AAV). This retrospective study included patients admitted to Renji Hospital from January 2017 to December 2023 who received induction treatment with either RTX or CYC. Effectiveness was evaluated by remission rate at month 6 (± 2 months), with additional subgroup analyses. Safety was assessed based on the occurrence of infections within 6 (± 2) months post-immunosuppression. Comparative analyses and logistic regression were performed using the Inverse Probability of Treatment Weighting (IPTW) method to bolster the reliability of the findings. A total of 293 patients were enrolled, with 124 treated with RTX and 169 with CYC for remission induction. The IPTW-weighted analysis indicated that patients administered RTX achieved a higher complete remission (CR) rate (41.4

Objectives:To describe the real-world efficacy and safety of obinutuzumab in a heterogeneous systemic lupus erythematosus (SLE) population, including severe or refractory manifestations. Methods:We retrospectively analyzed 56 SLE patients who received a single dose of obinutuzumab (1000 mg) at Renji Hospital, Shanghai Jiao Tong University School of Medicine between October 2021 and March 2024. Patients were followed for 48 weeks. Outcomes included the proportion of patients achieving definitions of remission in systemic lupus erythematosus (DORIS), Lupus Low Disease Activity State (LLDAS), clinical stable, and flare. Changes in SLEDAI-2K, anti-dsDNA, complement levels, B cell counts, glucocorticoid dose, and adverse events were assessed. Subgroup analyses were performed to address population heterogeneity. Results:At baseline, 35.7% of patients were newly diagnosed, 55.4% had relapsing/refractory disease, and 8.9% were on maintenance therapy. By week 48, 37.5% achieved DORIS remission, 32.1% LLDAS, and 19.6% remained clinically stable. Mean SLEDAI-2K decreased from 11.75 ± 9.31 (range: 0 to 46) to 1.45± 1.93 (range: 0 to 8). Among 15 lupus nephritis patients, 86.7% achieved complete renal response. Significant hematologic improvement was observed in autoimmune hemolytic anemia and thrombocytopenia. B cell counts declined rapidly and began to repopulate from week 36. Glucocorticoids tapered from 43.04 ± 18.19 (range: 0 to 60) to 8.95 ± 9.78 (range: 0 to 50) mg/day. Obinutuzumab was well tolerated, with infections observed in 14 cases (25.0%) and infusion reactions in 4 cases (7.1%). Conclusion:Obinutuzumab showed favorable efficacy and safety in SLE, including severe/refractory manifestations, suggesting potential benefits for difficult-to-treat patients.

BACKGROUND:Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder with unknown etiology. The absence of reliable biochemical and imaging markers often delays diagnosis and limits treatment effectiveness. As metabolic reprogramming is increasingly recognized as a hallmark of ALS, a comprehensive untargeted metabolomics analysis was employed to identify critical metabolic perturbations in ALS and explore novel candidate biomarkers with potential utility in clinical diagnosis. METHODS:Plasma from two independent cohorts comprising 399 participants (170 ALS patients, 200 healthy controls, and 29 ALS-unrelated neurological disease controls) was included. Cohort 1 was recruited from Shanghai Jiao Tong University School of Medicine Affiliated Ruijin Hospital (April 2020-September 2022), and cohort 2 from Sichuan Academy of Sciences-Sichuan Provincial Hospital, Ruijin Hospital, Shanghai Jiaotong University Affiliated Sixth People's Hospital, and The First Affiliated Hospital of Dalian Medical University (October 2022-February 2023). Gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS)-based metabolomics approaches were used to identify metabolic alterations and potential diagnostic biomarkers for ALS. Complementary multivariable and univariable statistical approaches were applied to characterize disease-specific metabolic reprogramming in ALS. In addition, the receiver operating characteristic (ROC) curve was used to assess the discriminatory power of differential metabolites, and binary logistic regression analysis was used to construct a multivariate biomarker model. RESULTS:Metabolic changes of ALS were mainly observed in amino acids, fatty acyls , and purines. Inosine and hypoxanthine were found to be the most significantly and critically dysregulated metabolites in ALS. Aminoacyl-transfer ribonucleic acid (tRNA) biosynthesis and amino acid metabolism were regarded as the most significantly perturbed pathways. Across both cohorts, 26 metabolites were consistently changed. Notably, a biomarker panel comprising hypoxanthine, inosine, and trigonelline was constructed using binary logistic regression, achieving excellent diagnostic performance in distinguishing ALS from controls, with an area under the ROC curve of 0.982 in cohort 1 (sensitivity 0.970, specificity 0.940) and 0.934 in cohort 2 (sensitivity 0.942, specificity 0.791). CONCLUSION:The disturbed pathways and biomarker candidates identified in this study may provide novel insights into ALS pathogenesis and improve diagnostic strategies.

Mitochondrial dynamics plays a crucial role in the occurrence and development of non-alcoholic fatty liver diseases (NAFLD). SENP1, a SUMO-specific protease, catalyzes protein de-SUMOylation and involves in various physiological and pathological processes. However, the exact role of SENP1 in NAFLD remains unclear. Therefore, we investigated the regulatory role of SENP1 in mitochondrial dynamics during the progression of NAFLD. In the study, the NAFLD in vivo model induced by high fat diet (HFD) and in vitro model induced by free fatty acids (FFA) were established to investigate the role and underlying mechanism of SENP1 through detecting mitochondrial morphology and dynamics. Our results showed that the down-regulation of SENP1 expression and the mitochondrial dynamics dysregulation occurred in the NAFLD, evidenced as mitochondrial fragmentation, up-regulation of p-Drp1 ser616 and down-regulation of MFN2, OPA1. However, over-expression of SENP1 significantly alleviated the NAFLD, rectified the mitochondrial dynamics disorder, reduced Cyt-c release and ROS levels induced by FFA or HFD; moreover, the over-expression of SENP1 also reduced the SUMOylation levels of Drp1 and prevented the Drp1 translocation to mitochondria. Our findings suggest that the possible mechanisms of SENP1 were through rectifying the mitochondrial dynamics disorder, reducing Cyt-c release and ROS-mediated oxidative stress. The findings would provide a novel target for the prevention and treatment of NALFD.

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

Autoimmune encephalitis (AE) comprises immune-mediated neuroinflammatory disorders presenting diverse neuropsychiatric symptoms and antibody-specific manifestations. Despite standard immunotherapy, residual disability, treatment intolerance, and relapse risks highlight unmet clinical needs. Telitacicept, a dual target fusion protein that inhibits B-lymphocyte stimulator (BLyS) and a proliferation-inducing ligand (APRIL), suppresses pathogenic B cell activation and autoantibody production, presenting a mechanism-driven therapeutic potential for AE management. Three AE cases with distinct therapeutic complexities are detailed in our study: (1) An anti-N-methyl-D-aspartate receptor (NMDAR) antibody-positive patient experienced recurrent relapses and was a comorbid individual with upper gastrointestinal bleeding. (2) An anti-leucine-rich glioma inactivated 1 (LGI1) antibody patient resisted corticosteroids, intravenous immunoglobulin, and ofatumumab treatment. (3) A newly diagnosed, anti-LGI1 antibody and anti-contactin-associated protein 2 (CASPR2) antibody dual-positive patient required sequential therapy to consolidate the remission and facilitate prednisone tapering. Telitacicept administration achieved symptom remission across all cases, accompanied by reduced antibody titers and stable outcomes over six months. Our case series evaluates the use of telitacicept in AE patients with varied antibody subtypes, particularly for patients with relapsed or refractory disease, intolerance to CD20-targeted agents, or steroid-related complications. Moreover, telitacicept may serve as an effective sequential therapy to sustain remission and reduce long-term steroid dependency.

Objective:Rituximab remains the standard-of-care anti-CD20 therapy for anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Obinutuzumab, a next-generation, glycoengineered anti-CD20 monoclonal antibody with enhanced B-cell-depleting capacity, may offer superior efficacy. We evaluated the efficacy and safety of reduced-dose obinutuzumab in 16 patients with active, refractory AAV at a single center in China. Methods:In this retrospective chart review, we evaluated 16 consecutive patients who received reduced-dose obinutuzumab (most commonly 1,000 mg for induction) after failure to achieve remission with cyclophosphamide (CTX) and/or rituximab (RTX) or who presented with severe, treatment-naïve disease. Primary endpoints were complete remission (CR) rates at 24 and 76 weeks. Secondary endpoints included changes in renal function, inflammatory biomarkers, and immune reconstitution. Adverse events were prospectively recorded. Results:The median age at obinutuzumab initiation was 44.5 years (IQR 31-54.3); 10 (62.5%) were men. The mean Birmingham Vasculitis Activity Score (BVAS) was 13.5 ± 6.4. There were 12 patients (75%) who had relapsing disease refractory to CTX/RTX, whereas four treatment-naïve patients presented with multiorgan failure. CR was achieved in 8/16 patients (50%) at week 24 and 13/16 patients (81.3%) at week 76. Obinutuzumab induced rapid clinical remission, suppressed systemic inflammation, achieved peripheral B-cell depletion, rendered ANCA-negative, and improved renal and pulmonary outcomes. No severe infections occurred. Seven patients (43.8%) developed treatment-emergent infections, predominantly respiratory (75%). Conclusion:Reduced-dose obinutuzumab demonstrates sustained remission in refractory or relapsing active AAV, achieving high long-term remission rates with an acceptable safety profile. No severe invasive infections were observed.

The positive detection rate of MRI in autoimmune encephalitis (AIE) patients is low, often failing to make a rapid and accurate localization diagnosis. Both 18F-DPA714 and 18F-FDG PET imaging techniques have shown their advantages in the diagnosis of AIE. Therefore, the aim of this study was to conduct a head-to-head comparison of the diagnostic value between 18F-DPA714 and 18F-FDG PET in patients with AIE. This cross-sectional study included 23 antibody-positive and 2 possible antibody-negative AIE patients, along with 10 healthy controls. All patients underwent sequential 18F-DPA714 PET/MRI and 18F-FDG PET/CT examinations within one week. A follow-up of 6 to 12 months after the baseline examinations was performed to assess the change of patients' clinical symptoms. Positive findings for 18F-DPA714 PET were defined as Z-score above 2.0 in the corresponding brain regions of healthy controls. Positive results for 18F-FDG PET were indicated by the Z-score above 2.0 or below -2.0 obtained after comparison with the normal population database. Both 18F-FDG PET and 18F-DPA714 PET showed higher positivity rates than MRI (81