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Introduction: This case describes successful response to efgartigimod in the treatment of myasthenic crisis secondary to paraneoplastic disease, and in the perioperative setting. Methods: An elderly female presented with speech difficulties, cessation of eating and 10kg weight loss over 4 months. Results: Examination revealed ptosis, dysarthria, nasal speech, and weakness in limbs and neck flexors. Single fiber electromyography demonstrated abnormal jitter response in the orbicularis oculi muscle. Nicotinic acetylcholine receptor antibodies were detected in serum. The patient was diagnosed with very-late-onset myasthenia gravis (MG) in a myasthenic crisis and later required intubation and admission to intensive care but was unresponsive to plasma exchange. Paraneoplastic disease was suspected and computed tomography revealed a bladder mass. Efgartigimod 10 mg/kg was administered intravenously to stabilize her condition before surgery. The patient's Myasthenia Gravis Activities of Daily Living (MG-ADL) score decreased from 19 to 14 after the first dose and she subsequently underwent surgical removal of the bladder tumor without complication. Her condition continued to improve post-operatively with completion of the first treatment cycle. Four cycles of efgartigimod over 10 months resulted in an MG-ADL score of 3. Discussion: Efgartigimod may be a novel treatment for perioperative management of MG, myasthenic crisis, and paraneoplastic MG. Further study is warranted. [ABSTRACT FROM AUTHOR]

Thyrotropin receptor antibodies (TRAb) are specific for Graves' disease (GD) and play a crucial role in the pathogenesis of GD. TRAb assays have recently been greatly improved. This review discusses the clinical application of TRAb in the differential diagnosis of hyperthyroidism, the prognosis of GD, GD in gestation and pediatrics, and GD related ophthalmopathy (GO). In addition to the classical competition and bioassays, a new bridging assay has emerged for TRAb assays. TRAb is the main pathogenic mechanism of hyperthyroidism in GD. Treated GD still has a high rate of recurrence and even a short-term surge of TRAb, leading to rapid deterioration of GO. Fetal goiter may be associated with elevated maternal TRAb during pregnancy, overtreatment may lead to fetal hypothyroidism. Pediatric patients with GD have high TRAb, poor remission from treatment, and insignificant manifestations of GO. TRAb is significantly correlated with GO activity and severity. Currently, TRAb assay has high specificity and sensitivity and can be used directly to identify the cause of hyperthyroidism. TRAb can be used to predict recurrence of drug treated GD or progression of GO after RAI therapy. TRAb should be measured regularly for GD in gestation to guide anti-thyroid medication to avoid thyrotoxicosis or hypothyroidism in the fetus. Monitoring TRAb in pediatric GD may help control the progression of GO. TRAb assay is an important guide for the treatment of GO. [ABSTRACT FROM AUTHOR]

Objective: This article reviews clinical trial data that assesses the safety, efficacy, and clinical application of spesolimab, an interleukin-36 (IL-36) blocker, for the treatment of generalized pustular psoriasis (GPP). Data sources: A review of the literature was conducted using the search terms: "spesolimab," "BI 655130," and "spevigo" in MEDLINE (PubMed) and Clinicaltrials.gov from January 1, 1950 to October 31, 2023. Study selection and data extraction: Relevant articles in English relating to the pharmacodynamics, pharmacokinetics, efficacy, and safety of spesolimab were included. Data Synthesis: In one phase 2 clinical trial evaluating single dose IV spesolimab for GPP flares at day 8, 54% of patients receiving spesolimab had a GPP physician global assessment (GPPGA) pustulation subscore of 0, and 43% had a GPPGA total score of 0 compared with 6% and 11% for the placebo group, respectively. Another phase 2 clinical trial assessing subcutaneous spesolimab found 23% of patients in low-dose, 29% in medium-dose, and 10% of high-dose spesolimab had flares by week 48 compared with 52% of the placebo group. Hazard ratios for time to GPP flare compared with placebo were 0.16 (P = 0.0005), 0.35 (P = 0.0057), and 0.47 (P = 0.027) for the spesolimab groups, respectively. Infection rates were similar across treatment and placebo groups, and severe adverse events such as drug reactions with eosinophilia and systemic symptom (DRESS), cholelithiasis, and breast cancer occurred with spesolimab. Relevance to Patient Care and Clinical Practice in Comparison to Existing Drugs: Spesolimab is a first-in-class IL-36 monoclonal antibody receptor antagonist approved for the treatment of acute GPP flares. It is a safe and effective therapeutic agent in preventing future GPP flares, with no current comparator trials with other GPP agents. Conclusion: Spesolimab is a safe and effective treatment for acute GPP flares in adults. Future clinical trials can establish safety and efficacy compared with other agents. [ABSTRACT FROM AUTHOR]

Cancer-associated fibroblasts (CAFs) are a crucial component in the tumor microenvironment (TME) of peritoneal metastasis (PM), where they contribute to tumor progression and metastasis via secretion of interleukin-6 (IL-6). Here, we investigated the role of IL-6 in PM of gastric cancer (GC) and assessed whether anti-IL-6 receptor antibody (anti-IL-6R Ab) could inhibit PM of GC. We conducted immunohistochemical analysis of IL-6 and α-smooth muscle (α-SMA) expressions in clinical samples of GC and PM, and investigated the interactions between CAFs and GC cells in vitro. Anti-tumor effects of anti-IL-6R Ab on PM of GC were investigated in an orthotopic murine PM model. IL-6 expression was significantly correlated with α-SMA expression in clinical samples of GC, and higher IL-6 expression in the primary tumor was associated with poor prognosis of GC. Higher IL-6 and α-SMA expressions were also observed in PM of GC. In vitro, differentiation of fibroblasts into CAFs and chemoresistance were observed in GC cells cocultured with fibroblasts. Anti-IL-6R Ab inhibited the progression of PM in GC cells cocultured with fibroblasts in the orthotopic mouse model but could not inhibit the progression of PM consisting of GC cells alone. IL-6 expression in the TME was associated with poor prognosis of GC, and CAFs were associated with establishment and progression of PM via IL-6. Anti-IL-6R Ab could inhibit PM of GC by the blockade of IL-6 secreted by CAFs, which suggests its therapeutic potential for PM of GC. [ABSTRACT FROM AUTHOR]

Introduction/Aims: Myasthenia Gravis (MG) is a common neuromuscular junction disorder that is primarily mediated by anti-acetylcholine receptor antibodies (AChR-Ab). However, using AChR-Ab titers to predict MG severity and improvement remains controversial. This study aims to explore the relationship between AChR-Ab titers and AChR-Ab rate of change (RR-AChR-Ab, %) and MG scores. Methods: We used a prospective study approach, and included 62 patients with generalized MG (GMG) who were positive for AChR-Ab. We measured AChR-Ab titers, MGFA-QMGS, and MG-ADL scores at baseline (before treatment) and at 3 and 6 months into treatment. Pearson and Spearman correlation analyses were used to study the relationships between changes in AChR-Ab titers, rates of change, and MG scores. Results: (1) At baseline, there was no correlation between AChR-Ab titers and age, duration of illness, gender, MGFA classification, or presence of thymic abnormalities. (2) The trend of decreasing AChR-Ab titers matched the trend of reduced QMGS and ADL scores. (3) Six months into treatment,there was a correlation between AChR-Ab titer changes and changes in ADL scores. (4) Three months into treatment, RR-AChRAb showed a correlation with the rate of change in ADL at the same time point. Conclusion: We found the trend of decreased AChR-Ab titers after standardized treatment that was consistent with reductions in QMGS and ADL scores. Additionally, the rate of change in AChR-Ab titers at 3 months and the change in AChR-Ab titers at 6 months into treatment did reflect improvements in activities of daily living for MG patients. [ABSTRACT FROM AUTHOR]

Objective: This study aims to delineate the clinical features underlying the concurrent disease of neuromyelitis optica spectrum disorder (NMOSD) and myasthenia gravis (MG), and to identify efficacious therapeutic strategies. Background: NMOSD and MG are uncommon autoimmune diseases that infrequently co-exist. Despite previous reports, a consensus on treating NMOSD concurrent with MG is lacking. Methods: We present the case of a 55-year-old female with both anti-aquaporin-4 (AQP4) antibody-positive NMOSD and anti-acetylcholine receptor (AChR) antibody-positive MG, who achieved stable disease control following treatment with inebilizumab without significant adverse effects. We also conducted a literature review to evaluate the clinical profile of this comorbidity. Results: Our review identified 85 patients with concurrent NMOSD and MG. In 70 well-documented cases, MG predated NMOSD in 60 (85.8%) cases, with 42 (70%) patients having undergone thymectomy. Six (8.6%) patients were first diagnosed with NMOSD, and then thymectomy was performed in 2 (33.3%) MG patients. For NMOSD treatment, although most patients received steroid hormones and immunosuppressive agents, quite a few patients had persistent severe disability. Additionally, of 44 patients with clear records of disease recurrence, 31 patients(70.5%) experienced frequent relapses of optic neuritis and myelitis, ranging from 1 to 15 attacks, averaging five. The manifestations of MG are mainly included fatigability, diplopia, and blepharoptosis, with symptoms well-controlled in most patients. Our patient treated with inebilizumab for 1 year and no relapse was recorded to date. Conclusions: Though MG typically precedes NMOSD and thymectomy is frequently performed, it is not a prerequisite for NMOSD development but may represent a potential risk factor. MG generally follows a benign course, in contrast to the more aggressive nature of NMOSD. The utility of biological agents such as inebilizumab for patients with both NMOSD combined with MG warrants further attention. [ABSTRACT FROM AUTHOR]

Background: A novel and rapid cell-based bioassay, Turbo TSI, for measurement of thyroid-stimulating immunoglobulins (TSI) was recently reported. An assessment of the analytical performance of this TSI bioassay is described herein. Methods: Thawed cells from Turbo TSI kits were treated with different concentrations of a World Health Organization (WHO) international standard (IS) TSI-positive serum. TSI was measured as a function of luciferase activity measured as relative light units (RLU) and converted into international units per liter (IU/L). Analytical performance studies were performed on numerous samples, over multiple days, by two users at two sites. Results: The limit of blank, limit of detection and limit of quantitation were determined to be 0.007 IU/L, 0.014 IU/L, and 0.021 IU/L, respectively. Receiver operator characteristics (ROC) analysis determined the cut-off to be 0.0241 IU/L with an area under the curve of 0.984. The linear range was shown to be from 0.015 to 11.958 IU/L. The intra-laboratory precision was ≤15%CV. The overall reproducibility of the assay was ≤20%CV for five concentrations (0.06 to 5.16 IU/L). Interference and cross reactivity studies with a variety of substances showed that the assay was robust. The Turbo TSI bioassay demonstrated 95.2% (95% CI 83.3-98.1) positive percent agreement and 94.8% (95% CI 90.9-97.1) negative percent agreement with an FDA-cleared bioassay (Thyretain ® TSI) using serum from 295 patients with autoimmune thyroid disease. Conclusions: The Turbo TSI bioassay exhibits excellent analytical performance and a high level of reproducibility. The performance compared well with Thyretain ® TSI, an FDA-cleared TSI bioassay. [ABSTRACT FROM AUTHOR]

Gonorrhea, caused by the human-restricted pathogen Neisseria gonorrhoeae, is a commonly reported sexually transmitted infection. Since most infections in women are asymptomatic, the true number of infections is likely much higher than reported. How gonococci (GC) colonize women's cervixes without triggering symptoms remains elusive. Using a human cervical tissue explant model, we found that GC inoculation increased the local secretion of both proinflammatory (IL-1β and TNF-α) and antiinflammatory (IL-10) cytokines during the first 24 hours of infection. Cytokine induction required GC expression of Opa isoforms that bind the host receptors carcinoembryonic antigen-related cell adhesion molecules (CEACAMs). GC inoculation induced NF-κB activation in both cervical epithelial and subepithelial cells. However, inhibition of NF-κB activation, which reduced GC-induced IL-1β and TNF-α, did not affect GC colonization. Neutralizing IL-10 or blocking IL-10 receptors by antibodies reduced GC colonization by increasing epithelial shedding and epithelial cell-cell junction disassembly. Inhibition of the CEACAM downstream signaling molecule SHP1/2, which reduced GC colonization and increased epithelial shedding, decreased GC-induced IL-10 secretion. These results show that GC induce local secretion of IL-10, a potent antiinflammatory cytokine, at the cervix by engaging the host CEACAMs to prevent GC-colonizing epithelial cells from shedding, providing a potential mechanism for GC asymptomatic colonization in women. [ABSTRACT FROM AUTHOR]

We present two cases of a rare thymic tumor presenting with ocular myasthenia gravis. Patient A was a male in his 40s who presented with bilateral diplopia. Investigations revealed negative myasthenic antibodies and positive jitter on single fiber electromyography. Patient B was a female in her 20s who presented with bilateral and fluctuating ptosis and diplopia, and was found to have positive acetylcholine receptor antibodies. Both patients demonstrated thymic hyperplasia on computed tomography chest and underwent robotic thymectomy. Pathology of the excised thymic tissue confirmed thymolipoma. We discuss the incidence, presentation, and management of thymolipomatous myasthenia gravis and present robotic thymectomy as a minimally invasive surgical treatment for thymolipoma. [ABSTRACT FROM AUTHOR]

The usefulness of current diagnostic approaches in children with suspected autoimmune encephalitis is unknown. We aimed to assess the diagnosis of autoimmune encephalitis in clinical practice and to compare the performance of two international diagnostic algorithms (one intended for patients of any age [general], the other intended for paediatric patients), with particular emphasis on the evaluation of patients with probable antibody-negative autoimmune encephalitis because this diagnosis suggests that immunotherapy should be continued or escalated but is difficult to establish. We did a prospective cohort study that included all patients (<18 years of age) with suspected autoimmune encephalitis recruited at 40 hospitals in Spain whose physicians provided clinical information every 6 months for 2 years or more. Neural antibody testing to confirm diagnosis of antibody-positive autoimmune encephalitis was done at Institut d'Investigacions Biomèdiques August Pi i Sunyer-Hospital Clínic, Barcelona. Patients were classified according to the most probable diagnosis at last follow-up into four prespecified categories. We used multivariable logistic analysis to assess a potential association between immunotherapy and outcome in individuals with probable antibody-negative autoimmune encephalitis. We also did a retrospective analysis of agreement, assessed with the kappa index, between diagnoses made according to the general and paediatric diagnostic algorithms. Between June 1, 2013, and May 31, 2021, 729 children (mean age 7·1 years [SD 4·9]; 383 boys [53%], 346 girls [47%]) with suspected autoimmune encephalitis were recruited. After a median follow-up of 36 months (IQR 26–60), patients were classified according to their most probable diagnosis: definite autoimmune encephalitis or well defined inflammatory or autoimmune disorders (n=230 [32%]); CNS infections (n=112 [15%]); inflammatory CNS disorders of unknown cause (n=81 [11%], including three (4%) with a novel Klüver-Bucy-like syndrome; and non-inflammatory disorders (n=306 [42%]), which were predominantly epileptic or psychiatric disorders (177 [58%] of 306). Neural antibodies were detected in 150 (65%) of 230 patients who had definite autoimmune encephalitis; 127 (85%) of these 150 individuals had antibodies to the NMDA receptor or myelin oligodendrocyte glycoprotein (MOG). Agreement between algorithms was excellent (kappa index 0·99, 95% CI 0·97–1·00) for the diagnosis of children with antibody-positive autoimmune encephalitis, good (0·59, 0·54–0·65) for recommendations of empiric immunotherapy, and poor (0·29, 0·21–0·37) for the diagnosis of probable antibody-negative autoimmune encephalitis. Compared with the general algorithm, the paediatric algorithm included more patients in the probable antibody-negative autoimmune encephalitis category (173 vs 41). These patients included some of those who had a diagnosis of CNS inflammatory disorder of unknown cause at the last follow-up (80 of 81 with the paediatric algorithm vs 31 of 81 with the general algorithm), who might have benefitted from immunotherapy, and some of those diagnosed with a non-inflammatory disorder at the last follow-up (47 of 306 with the paediatric algorithm vs six of 306 with the general algorithm), who did not need immunotherapy. About a third of children with suspected autoimmune encephalitis eventually had confirmation of this diagnosis, or diagnosis of another well defined inflammatory disorder. Frequent mimics of autoimmune encephalitis were infectious, epileptic, and psychiatric disorders. Both algorithms performed well in the diagnosis of antibody-positive autoimmune encephalitis, but the paediatric algorithm under-recognised definite autoimmune encephalitis that can occur without autoantibodies and might have overdiagnosed patients with probable antibody-negative autoimmune encephalitis. By contrast, the general algorithm might have underdiagnosed patients with probable antibody-negative autoimmune encephalitis. Given that the diagnosis of probable antibody-negative autoimmune encephalitis has treatment implications, inaccuracies on this diagnostic category leads to overuse or underuse of immunotherapy. Instituto de Salud Carlos III, Fundació Clínic per la Recerca Biomèdica, The Edmond J Safra Foundation, and la Caixa Foundation. For the Spanish translation of the abstract see Supplementary Materials section. [ABSTRACT FROM AUTHOR]

Lesson: The delayed onset of thyroid eye disease is well recognised but less commonly perceived in routine clinical practice and this case report serves as a reminder for a high index of suspicion in at-risk patients. [ABSTRACT FROM AUTHOR]

Background: Alarmins mediate type 2 T helper cell (Th2) inflammation and serve as upstream signaling elements in allergic inflammation and autoimmune responses. The alarmin interleukin (IL)-25 binds to a multi-domain receptor consisting of IL-17RA and IL-17RB subunits, resulting in the release of Th2 cytokines IL-4, IL-5, IL-9 and IL-13 to drive an inflammatory response. Therefore, the blockage of IL-17RB via SM17, a novel humanized monoclonal antibody, offers an attractive therapeutic target for Th2-mediated diseases, such as asthma. Methods: Wild-type mice were stimulated with house dust mite (HDM) extracts for evaluation of SM17's pre-clinical efficacy in allergic asthma. The safety, pharmacokinectics (PK), pharmacodynamics (PD), and immunogenicity of intravenous (IV) doses of SM17 were assessed in a 2-part clinical study in healthy adult subjects. In Part A, 53 healthy participants were enrolled to receive a single IV dose of SM17 (2, 20, 70, 200, 400, 600, 1200 mg) or placebo. In Part B, 24 healthy subjects were enrolled to receive a single IV dose of SM17 every two weeks (Q2W; 200, 400, 600 mg) or placebo for a total of 3 doses. Results: Animal studies demonstrated that SM17 significantly suppressed Th2 inflammation in the bronchoalveolar lavage fluid and infiltration of immune cells into the lungs. In the Phase I clinical study, no drug-related serious adverse events were observed. Total SM17 exposure increased by approximately 60- to 188-fold with a 60-fold increase in dose from 20 to 1200 mg SM17. Upon administration of the third dose, mean accumulation ratios over 200-600 mg was 1.5 to 2.1, which confirms moderate accumulation of SM17. After Q2W dosing of SM17 over 4 weeks, total exposure increased in a dose-proportional manner from 200 mg to 600 mg SM17. Conclusion: In the pre-clinical studies, we demonstrated that SM17 is a potential therapeutic agent to treat allergic asthma. In the Phase 1 clinical trial, a single IV dose of SM17 up to 1200 mg and three Q2W doses up to 600 mg were well tolerated in healthy participants and demonstrated a favorable safety profile. The pre-clinical efficacy and clinical PK and immunogenicity results of SM17 support further clinical development. Clinical trial registration: https://clinicaltrials.gov/ , identifier NCT05332834. [ABSTRACT FROM AUTHOR]

Background: Thymoma-associated myasthenia gravis (TAMG) is a subtype of myasthenia gravis (MG) that is associated with more severe symptoms and a relatively poor prognosis. Eculizumab, an inhibitor to target human C5 component of the complement cascade, is considered a treatment option for refractory generalized MG (gMG). Objectives: To explore the safety and efficacy of eculizumab in patients with TAMG. Design: This is an observational multicenter real-world cohort study to assess TAMG who were treated with eculizumab from June 2023 to June 2024. Data sources and methods: Clinical features associated with thymoma-associated multi-organ autoimmunity (TAMA), Myasthenia Gravis Activities of Daily Living (MG-ADL) score, and the incidence of treatment-emergent adverse events (TEAEs) were prospectively collected. Results: Overall, 42 patients with gMG were treated with eculizumab at 5 research centers, of whom 22 patients with TAMG were finally included. This cohort had a mean age of 51.5 ± 12.1 years and an average disease duration of 4.0 ± 4.3 years. Regarding thymomas, the World Health Organization (WHO) histological classification was primarily B2 and B3 (63.7%), and Masaoka staging was predominantly IV (45.5%). Nine participants (40.9%) switched from efgartigimod to eculizumab aiming at a better clinical improvement and reducing steroid use. By week 12, the MG-ADL score decreased to 4.8 ± 4.7 (baseline: 11.7 ± 6.0), and the corticosteroid dose reduced to 23.2 ± 26.5 mg (baseline: 41.8 ± 63.9 mg). Two patients with TAMA showed significant improvement in skin lesions and thrombocytopenia. Two TEAEs were recorded including COVID-19 and herpes labialis infection. Four patients (18.2%) died of respiratory or circulatory failure owing to thymoma metastasis. Conclusion: This real-world study demonstrates the efficacy of eculizumab in achieving symptom control and corticosteroid reduction for TAMG. It may also be a therapeutic option for refractory TAMG and TAMA. Trial registration: NCT04535843. Plain language summary: Eculizumab in thymoma-associated myasthenia gravis Patients with unresectable thymomas tend to have more severe symptoms at a younger age, a higher frequency of myasthenic crisis (MC), longer respiratory support duration, and increased mortality compared to those without thymomas. Only a few case reports have explored the therapeutic efficacy of eculizumab in thymoma-associated myasthenia gravis (TAMG), which is a subtype of myasthenia gravis (MG) that is associated with anti-acetylcholine receptor antibodies. Using a multicenter, observational cohort of patients with generalized myasthenia gravis from China, we enrolled patients with TAMG who were refractory to immunotherapies and then switched to eculizumab. Our study revealed a significant improvement in the Myasthenia Gravis Activities of Daily Living (MG-ADL) score in patients with TAMG (7.4 points) by week 12. Moreover, this study demonstrated the efficacy and safety of eculizumab in the TAMG cohort, with most patients experiencing clinical improvement within 2 weeks and an average reduction in steroid dosage of approximately one-third in the first month. Further, we believe that this article will be of interest to the readership of your journal because it provides evidence-based findings that indicate that eculizumab has emerged as a viable treatment option not only for TAMG but also for thymoma-associated multiorgan autoimmunity (TAMA). [ABSTRACT FROM AUTHOR]

Quantifying glycated albumin (GA) levels in the blood is crucial for diagnosing diabetes because they strongly correlate with blood glucose concentration. In this study, a biotic/abiotic sandwich assay was developed for the facile, rapid, and susceptible detection of human serum albumin (HSA) and GA. The proposed sandwich detection system was assembled using a combination of two synthetic polymer receptors and natural antibodies. Molecularly imprinted polymer nanogels (MIP-NGs) for HSA (HSA-MIP-NGs) were used to mimic capture antibodies, whereas antibodies for HSA or GA were used as primary antibodies and fluorescent signaling MIP-NGs for the Fc domain of IgG (F-Fc-MIP-NGs) were used as a secondary antibody mimic to indicate the binding events. The HSA/anti-HSA/F-Fc-MIP-NGs complex, formed by incubating HSA and anti-HSA antibodies with F-Fc-MIP-NGs, was captured by HSA-MIP-NGs immobilized on the chips for fluorescence measurements. The analysis time was less than 30 min, and the limit of detection was 15 pM. After changing the anti-HSA to anti-GA (monoclonal antibody), the fluorescence response toward GA exceeded that of HSA, indicating successful GA detection using the proposed sandwich detection system. Therefore, the proposed system could change the detection property by changing a primary antibody, indicating that this system can be applied to various target proteins and, especially, be a powerful approach for facile and rapid analysis methods for proteins with structural similarity. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective Methods Results Conclusions Trial Registration Different definitions of thyroid dysfunction during pregnancy may lead to under or overtreatment. The aims of this study were to (1) define population‐based pregnancy‐specific reference ranges for thyroid dysfunction during early pregnancy in Nepal and assess the impact of antibody positivity, (2) quantify the diagnostic impact of population‐based reference ranges compared with current practice and (3) assess the determinants of thyroid function and antibody positivity.A total of 800 healthy pregnant women aged 20–40 years in the Bhaktapur municipality were included. Population‐based reference ranges for thyroid hormones levels were defined as 2.5th and 97.5th percentiles using competitive immunoluminometric assay design. Thyroid disease cases and those with recommended treatment indications were calculated using current non‐pregnancy new reference ranges. Multivariate regression analyses were performed to identify the determinants of thyroid hormones and antibody levels.Median gestational age was 11 weeks. The reference interval was 0.05–3.69 µLU/mL for thyroid stimulating hormone (TSH) and 8.89–15.28 pg/mL for free tetraiodothyronine (fT4) after excluding thyroid peroxidase antibody‐positive women. Compared with the current non‐pregnancy reference ranges, the new calculations increased the number of women who required treatment from 5 to 12 (0.9% increase). We identified 19 women (2.4%) who were positive for TSH receptor antibody (TRAb). We could not identify the determinants of TRAb positivity, and TRAb positivity was not associated with TSH or fT4 levels.We found meaningful changes using population‐based pregnancy‐specific TSH and fT4 reference intervals and encourage further studies in other low‐ and middle‐income settings. Our findings suggest that population screening for TRAb is not clinically meaningful.Clinical Trial Registration: U1111‐1183‐4093. [ABSTRACT FROM AUTHOR]

We report a case of a 60‐year‐old lady with metastatic follicular thyroid carcinoma (FTC) who was presented with thyrotoxicosis and heart failure symptoms after total thyroidectomy. Clinical features and investigations led to the diagnosis of functional metastatic FTC with concomitant thyrotoxicosis. Levothyroxine therapy was stopped, and she was treated with propylthiouracil (PTU) followed by serial radioiodine treatments (RAITs) with good control of thyrotoxicosis and metastases. Despite having a very high disease burden with metastatic FTC, she has been able to maintain her functional status thus far, 4.5 years after initial diagnosis. [ABSTRACT FROM AUTHOR]

Objective: To prepare a humanized monoclonal antibody against periostin and establish a stable cell line. Methods: Based on anti-periostin mouse monoclonal antibody developed by our laboratory, total RNA was extracted, and variable region sequences were obtained by RT-PCR amplification of VH and VL genes. The mouse antibody CDR region was transplanted into the human antibody framework receptor region, and the gene was subcloned into the expression vector PATX-GS2, and stably transfected into CHO cells. Monoclonal cell lines were obtained by MSX pressure screening and limited dilution. Results: VH and VL genes were amplified by RT-PCR, and the sequence of the light and heavy chain variable region were determined. Antibody humanization were successfully stablished by CDR transplantation method a murine antibody to a human framework, and a eukaryotic expression plasmid was constructed, which was transfected into CHO cells for expression, and human anti-periostin antibody was successfully obtained. ELISA and Western blot results showed that the humanized antibody had good anti-periostin activities and binding affinity. Conclusion: In this study, anti-periostin humanized monoclonal antibody has been successfully prepared, which can specifically bind to periostin proteins in vivo and have biological activity, providing scientific data for the precise treatment of retinal fibrosis, tissue and organ fibrosis, and malignant tumors. [ABSTRACT FROM AUTHOR]

PURPOSE: In metastatic colorectal cancer (mCRC), RAS mutations drive resistance to anti–epidermal growth factor receptor antibodies. It is unclear whether RAS mutations ever become clonally undetectable. METHODS: CO.26 was a phase II clinical trial that assessed durvalumab + tremelimumab in heavily pretreated mCRC. RAS mutation status was tracked over time using circulating tumor DNA (ctDNA) sequencing at baseline, week 8, and on progression. RESULTS: Among the 95 patients with KRAS/NRAS mutations in their archival tumor tissue, 6.3% (6/95) had undetectable RAS mutations in ctDNA collected at baseline or week 8 of the CO.26 study. Of these, 67% (4/6) of disappearances were transient, with the same mutation reappearing with progressive disease. In three cases, the simultaneous persistence of other preexisting CRC-associated truncal mutations could not be demonstrated, suggestive of low tumor shedding of ctDNA, leaving the incidence of true clonal reversion to RAS -wildtype (WT) possibly as low as 3.2% (3/95). Fewer patients in the neo- RAS -WT group (33%) had greater than four lesions at trial baseline compared with patients with persistent RAS mutations (75%), P =.046. The likelihood of synchronous metastases at cancer diagnosis (33% v 63%; P =.15) or liver metastases at trial baseline (50% v 68.5%; P =.17) was not significantly different between patients with disappearing versus persistent RAS mutations. Overall survival from stage IV diagnosis (hazard ratio, 0.77 [95% CI, 0.35 to 1.72]; P =.52) was not significantly different between those with disappearing versus persistent RAS mutations. The disappearance of RAS mutations was not associated with primary tumor sidedness (P =.41), archival BRAF/MEK/ERK -mutant status (P =.16/1.00/.09), nor baseline ctDNA HER2 amplifications (P = 1.00). CONCLUSION: We identified a 3.2%-6.3% prevalence of the neo- RAS -WT phenomenon in the CO.26 trial. However, 67% of apparent cases were transient with subsequent re-emergence. [ABSTRACT FROM AUTHOR]

Background: Several significant associations between certain Human Leukocyte Antigen (HLA) alleles and myasthenia gravis (MG) subtypes were established in populations from Western Europe and North America and, to a lesser extent, from China and Japan. However, such data are scarcely available for Eastern Europe. This study aimed to analyze the associations of HLA Class I and II alleles with MG and its serological subtypes (with anti-acetylcholine receptor autoantibodies, RAch+MG, and double-seronegative, dSNMG) in myasthenic patients of Romanian descent. Methods: We consecutively enrolled adult Romanian unrelated myasthenic patients, which were genotyped by next-generation sequencing for HLA-A, -B, -C, -DRB1 and -DQB1. The descent-matched controls were represented by two separate groups of random normal subjects genotyped for the main five HLA loci at the two-digit and four-digit levels, respectively, collected from the Allele Frequency Net Database. Results: A total of 40 patients (females: 80.00%; median age at onset: 42.5 years, range: 1–78; RAch+MG: 75.00%; dSNMG: 22.50%) were included. We were able to confirm previously acknowledged allelic associations: positive for HLA-B*08, DRB1*14:54 and DRB1*16:01 and negative for DRB1*13. However, we found some potential novel significant positive associations between MG and the HLA-A*02:36, B*47, B*73, B*44:27 and B*57:02 alleles. All alleles positively associated with MG remained significantly associated with RAch+MG, regardless of the patients' clinical and thymic heterogeneity. We found significant positive associations between dSNMG and the HLA-B*47, B*44:27 and DRB1*14:54 alleles that are shared with RAch+MG. Conclusions: These results suggest both distinct and common etiopathogenic mechanisms between dSNMG and RAch+MG. Our study pioneers allele associations in Romanian MG patients. [ABSTRACT FROM AUTHOR]

Imprinted proteins (IPs) are promising alternatives to natural recognition systems, such as biological receptors or antibodies. One of the crucial stages during development of IPs is removal of the template molecules from its complex with the protein. In this study, bovine serum albumin was imprinted in the presence of 4‐hydroxycoumarin (4‐HC); purification of IPs were carried out by dialysis, and fluorescence 3D spectroscopy was used to monitor the IP purification process. Excitation–emission matrix (EEM) was further investigated via several chemometric algorithms (principal component analysis [PCA], parallel factor analysis [PARAFAC], and independent components analysis [ICA]). We found that the models using PARAFAC and ICA worked better than those of PCA. It was shown that PARAFAC and ICA analyses allow not only to recognize IP sample with signal close to nonimprinted protein, but also to provide recommendations on the optimal dialysis time. [ABSTRACT FROM AUTHOR]

Graves’ disease (GD) is an autoimmune disease that can affect other tissues in addition to the thyroid gland. The clinical manifestations are a result of the impact of TSH receptor antibodies. Depending on the intensity of the immune response, in addition to hyperthyroidism, orbitopathy, dermatopathy and acropachy can also occur. Extrathyroidal manifestations of GD are most often the result of a more pronounced immune response. Dermatopathy is a rare extrathyroidal manifestation, with a prevalence of 0.5-4.3%, and when it occurs, it almost always accompanies orbitopathy (96%) and hyperthyroidism, while it is associated with a severe form of orbitopathy in 13-15% of cases. It is characteristic of long-standing disease and an intense autoimmune response. We present a case series of five patients with dysthyroid dermopathy. Our patients had different thyroid function disorders (hypo/hyperthyroidism), different forms of dermopathy, and varying times of onset during the disease. Association with orbitopathy and high TRAb concentrations were also present in all our patients. The effects of therapy applied for orbitopathy were monitored, which showed a favorable response on dermopathy, especially with the use of tocilizumab in some of our patients. [ABSTRACT FROM AUTHOR]

Autoimmune encephalitis is a rapidly progressive inflammatory brain disease. Gamma-aminobutyric acid type B (GABAB) receptor autoimmune encephalitis is a rare subtype characterized by distinct clinical features. Diagnosis can be especially challenging when typical limbic symptoms and neuroimaging findings are absent. This case report underscores the importance of identifying this condition and starting immunosuppressive treatment promptly. A 59-year-old man presented with gait disturbances, dysarthria, and severe ataxia without cognitive impairment. Initial examinations, including a brain MRI, were unremarkable, except for an elevated cell count and protein in the cerebrospinal fluid. Despite receiving initial empirical antiviral treatment, his symptoms worsened, prompting the administration of intravenous methylprednisolone and immunoglobulin. After these immunosuppressive therapies, the cerebellar symptoms showed gradual improvement. Subsequent testing for antibodies to the GABAB receptor was positive in both the serum and cerebrospinal fluid. Follow-up MRI revealed cerebellar atrophy, consistent with a diagnosis of GABAB receptor-associated acute cerebellitis. This case illustrates that cerebellar symptoms can occur in the absence of more common limbic manifestations in GABAB receptor autoimmune encephalitis. The progression of cerebellar atrophy following an initially normal MRI is a significant finding that offers supporting evidence for the diagnosis of cerebellitis. A review of the literature identified similar cases of acute cerebellitis without limbic symptoms, although neuroimaging abnormalities in the cerebellum were not reported. Our case underscores the importance of increased clinical awareness and consideration of autoimmune causes, even when neuroimaging appears normal. Early and appropriate immunosuppressive therapy may help change the course of the disease and enhance patient outcomes. [ABSTRACT FROM AUTHOR]

The application of extracellular vesicles (EVs) as vehicles for anti‐Parkinson's agents represents a significant advance, yet their clinical translation is hampered by challenges in efficient brain delivery and complex blood‐brain barrier (BBB) targeting strategies. In this study, we engineered dopamine onto the surface of adipose‐derived stem cell EVs (Dopa‐EVs) utilizing a facile, two‐step cross‐linking approach. This engineering enhanced neuronal uptake of the EVs in primary neurons and neuroblastoma cells, a process shown to be competitively inhibited by dopamine pretreatment and dopamine receptor antibodies. Notably, Dopa‐EVs demonstrated increased brain accumulation in mouse Parkinson's disease (PD) models. Therapeutically, Dopa‐EVs administration led to the rescue of dopaminergic neuronal loss and amelioration of behavioural deficits in both 6‐hydroxydopamine (6‐OHDA) and α‐Syn PFF‐induced PD models. Furthermore, we observed that Dopa‐EVs stimulated autophagy evidenced by the upregulation of Beclin‐1 and LC3‐II. These findings collectively indicate that surface modification of EVs with dopamine presents a potent strategy for targeting dopaminergic neurons in the brain. The remarkable therapeutic potential of Dopa‐EVs, demonstrated in PD models, positions them as a highly promising candidate for PD treatment, offering a significant advance over current therapeutic modalities. [ABSTRACT FROM AUTHOR]

Background and Purpose: Acetylcholine receptor antibody (AChR‐Ab) detection is crucial in myasthenia gravis (MG) diagnosis and, currently, the radioimmunoassay (RIA) is the gold standard. However, RIA may detect AChR‐Ab against nonpathogenic intracellular epitopes. In this study, we performed fixed cell‐based assay (F‐CBA) in RIA‐AChR‐Ab positive subjects without MG symptoms, to assess whether F‐CBA could show a higher specificity compared to RIA in detecting pathogenic Abs. Methods: We reviewed medical records of patients referred to our MG outpatient clinic because of RIA‐AChR‐Ab detection. MG diagnosis was based on clinical examination, electrophysiology and Ab detection. AChR‐Abs were tested by RIA in the whole cohort. Serum samples from RIA‐positive asymptomatic subjects were retested by F‐CBA. Results: Of 605 subjects who tested RIA‐AChR‐Ab positive, MG diagnosis was confirmed in 599. Six subjects were RIA‐AChR‐Ab positive although they had never had MG symptoms; in four of these subjects AChR‐Abs were not detected by F‐CBA, whereas the remaining two (both non‐MG thymoma cases) were positive also by F‐CBA. Conclusions: RIA false positivity for AChR‐Ab is very rare. Previous literature has demonstrated that F‐CBA has higher sensitivity than RIA for MG, especially in ocular cases. Our preliminary results show that, in rare instances, F‐CBA may be more specific than RIA for MG diagnosis. [ABSTRACT FROM AUTHOR]

The Junín virus (JUNV) is one of the New World arenaviruses that cause severe hemorrhagic fever. Human transferrin receptor 1 (hTfR1) has been identified as the main receptor for JUNV for virus entry into host cells. To date, no treatment has been approved for JUNV. Herein, we investigated 12 anti-hTfR1 VHH (variable domain of the heavy chain of heavy-chain antibody) antibodies and confirmed their interaction with hTfR1. Most of them could bind to the hTfR1 apical domain, which is the glycoprotein 1 (GP1) binding domain of JUNV. Among them, 18N18 exhibited neutralizing activity against both the human immunodeficiency virus (HIV)-vectored lentiviral Junín pseudoviruses and the recombinant vesicular stomatitis virus (VSV)-vectored Junín pseudoviruses. We also verified that 18N18 blocked the interaction between hTfR1 and JUNV GP1. In addition, 18N18 could neutralize another New World arenavirus, the Machupo virus. Using AlphaFold 3-based simulation of 18N18–hTfR1 docking, we determined that 18N18's binding epitope was located at the JUNV GP1 binding epitope. 18N18 represents a candidate for JUNV treatment and provides a potential approach that could be applied to New World arenaviruses. [ABSTRACT FROM AUTHOR]

Tocilizumab (TCZ) which is a humanized interleukin (IL)-6 receptor antibody has been increasingly widespread used in rheumatology practice. TCZ-related hypofibrinogenemia is a not well-described side effect, but awareness seems to be incresing as publications on this topic are also becoming more frequent. Our aim in this study was to determine the frequency, timing, and approach to TCZ-related hypofibrinogenemia in rheumatic diseases. We retrospectively screened our patients who received TCZ for inflammatory rheumatic diseases and studied serum fibrinogen at least once before and/or after drug administration. We recorded and analyzed demographic features (age, gender, diagnosis), comorbidities, laboratory parameters, management, and outcome data. 30 patients who received TCZ due to rheumatological diseases and had at least one fibrinogen level were included in this study. 73.3% were female and median age was found to be 65 (42–82) years, with median disease duration of 148 (36–500) months. 90% of the patients received TCZ for RA and 10% for GCA. We examined the fibrogen levels at an average of 24 months (min 1 max 108) following the start of TCZ treatment. The study group was divided into those with normal fibrinogen levels (normal fibrinogen group) and those with low fibrinogen levels (lowfibrinogen group). In total, hypofibrinogenemia was found in 14 (46.6%) patients. Median serum fibrinogen level in the low fibrinogen group after TCZ was calculated to be 151.5 mg/dl (min 92 max 171). Most patients were asymptomatic (71.4%). Ecchymoses were in seen 4 (28,6%) patients. No major bleeding were seen. TCZ was discontinued in 5 out of 14 patients (35.7%), while 9 out of 14 patients (64.3%) were closely followed. Outcomes regarding fibrinogen levels (11 out of 14) were as follows: increase in 4 and not checked in one after cessation of the drug, 3 spontaneous increases under the drug, and 3 persistently low levels on TCZ treatment. We found no difference in terms of gender (p = 0.417), platelets (p = 0.343), ESR (p = 0.448), and CRP (p = 0.660) at the time of TCZ initiation between groups. TCZ-related hypofibrinogenemia is more frequent than expected with occurence in both the early and late stages of treatment. Further research is required to determine whether to regularly measure fibrinogen levels in patients using TCZ and how to treat patients with hypofibrinogenemia. [ABSTRACT FROM AUTHOR]

Denosumab is a human IgG2 monoclonal antibody against receptor activator of nuclear factor kappa‐B ligand (RANKL) for the treatment of osteoporosis and bone loss. HLX14 is a proposed biosimilar of denosumab. This randomized, parallel‐group, two‐part, phase I study aimed to compare the pharmacokinetics, pharmacodynamics, safety, and immunogenicity of HLX14 with reference denosumab in Chinese healthy adult male participants. In Part 1, participants were randomized 1:1 and given HLX14 or reference denosumab sourced from the European Union (EU). In double‐blind Part 2, participants were randomized 1:1:1:1 to receive HLX14 or denosumab sourced from the United States, EU, or China. All study drugs were administered via subcutaneous injection at a single dose of 60 mg. The primary endpoints were area under the serum drug concentration–time curve from time 0 to the last concentration‐quantifiable time t (AUC0–t), maximum serum drug concentration (Cmax), and area under the serum drug concentration–time curve from time 0 to infinity (AUC0–inf). Twenty‐four participants were randomized in Part 1 and 228 in Part 2. The 90% confidence intervals of geometric mean ratio of AUC0–t, Cmax, and AUC0–inf between HLX14 and denosumab from different sources fell within the pre‐specified similarity margins of 0.80–1.25 (AUC0–t, 0.91–1.13; Cmax, 0.91–1.13; AUC0–inf, 0.91–1.12), demonstrating pharmacokinetic similarity. No notable difference was observed among treatment groups in pharmacodynamics, safety, or immunogenicity. HLX14 demonstrated highly similar pharmacokinetic characteristics with comparable pharmacodynamics, safety, and immunogenicity to denosumab, supporting its further investigation as a potential denosumab biosimilar. [ABSTRACT FROM AUTHOR]

N-methyl-D-aspartate receptor encephalitis (NMDARE) presents serious neurological manifestations such as reduced consciousness, seizures, and movement disorders, which can escalate to coma or severe autonomic dysfunction. Treatment typically involves immunotherapy and tumor removal to mitigate the autoimmune response. Timely diagnosis and treatment are critical to prevent severe neurological impairment or death. Memantine, an NMDA receptor antagonist, has shown variable effectiveness in treating NMDARE according to several case reports, yet comprehensive analyses remain scarce. This mini review draws on five literature sources and eight case studies from databases including PubMed, Embase, the Cochrane Library, and Web of Science, highlighting both the potential and risks of memantine as an adjunct therapy. We explore how memantine may reduce symptoms by blocking excessive NMDA receptor (NMDAR) antibody binding, while potentially worsening symptoms by reducing extracellular NMDAR availability, thus impairing neuronal communication. This dual effect calls for further investigation into the optimal use and duration of memantine treatment in NMDARE management. [ABSTRACT FROM AUTHOR]

The pathomechanisms of autonomic disorders in systemic lupus erythematosus (SLE) remain unclear. We herein report a patient with SLE who developed autonomic disorders presumably caused by autoimmune autonomic ganglionopathy (AAG). A 42-year-old woman with SLE under treatment with corticosteroids and hydroxychloroquine was admitted for recurrence of SLE with thrombocytopenia and nephritis. On admission, she presented with weight loss, orthostatic dizziness, abdominal distension, and difficulty urinating. Marked intestinal dilatation, kidney swelling, bilateral hydronephrosis, and ureteral dilatation were noted on ultrasonography and computed tomography. No evidence of obstruction was observed in the intestines, urinary tracts, or bladder. Transverse myelitis was also ruled out by magnetic resonance imaging. After starting the treatment for the recurrent SLE (intravenous immunoglobulin and methylprednisolone pulse therapy, followed by high-dose oral corticosteroid, mycophenolate mofetil, and tacrolimus), orthostatic dizziness, abdominal distension, and difficulty urinating subsided along with increases in platelet count and decreases in urinary protein. The intestinal dilatation, hydronephrosis, and ureteral dilatation improved. We inferred that her SLE was complicated by AAG based on a positive anti-ganglionic acetylcholine receptor antibody. This case suggested that AAG should be considered as a type of autonomic disorder in SLE. [ABSTRACT FROM AUTHOR]

The thyroid eye disease (TED) of Graves disease is associated with high titers of stimulating TSH receptor antibodies, retro-orbital inflammation, fibroblast release of cytokines and chemokines, and adipogenesis, which in turn leads to proptosis, muscle fibrosis, and dysfunction. Part of this scenario is the induction of fibroblast proliferation and autophagy secondary to synergism between the TSH receptor (TSHR) and the insulin-like growth factor-1 receptor (IGF-1R). While TED is well associated with thyroid-stimulating antibodies to the TSHR, which is also well expressed on fibroblasts, in fact the TSHR reactome has a variety of TSHR antibodies with varying biological activity. Therefore, we have now evaluated the possible role of neutral TSHR antibodies (N-TSHR-mAbs), directed at the hinge region of the TSHR, which do not induce cell proliferation but are known to have effects on multiple proteins in thyroid cells including stress-related signaling molecules. We examined the consequences of an N-TSHR-mAb acting on TSHR-expressing fibroblasts and found marked cell stress, which initiated signaling pathways involving inflammasome activation. This response ended in widespread cell death by pyroptosis through activation of caspase 8 and gasdermin D. Hence, not only can stimulating TSHR autoantibodies influence TED inflammation but the N-TSHR antibodies, representing more of the reactome, may also exaggerate the retro-orbital inflammatory response seen in TED. [ABSTRACT FROM AUTHOR]

Context The efficacy of tocilizumab (TCZ) in treating Graves orbitopathy (GO) remains uncertain due to the small sample sizes of earlier studies, and there is a lack of research on the drug for juvenile GO. Objective To evaluate the effectiveness of TCZ in treating GO that is resistant to conventional therapy. Design This observational study at a tertiary care center included 79 Chinese GO patients, 15 of whom were pediatric patients, with 52 of these patients having moderate to severe active GO (all adult patients having steroid-resistant GO). Intravenous infusion of TCZ 8 mg/kg was given every 28 days for 4 months. Changes from baseline in visual acuity (VA), intraocular pressure (IOP), proptosis, clinical activity score (CAS), and thyrotropin receptor antibody (TRAb) levels throughout TCZ therapy were assessed at baseline (T0), the fifth month (T4), and follow-up (T5). Additionally, improvements in CAS by at least 2 points and CAS < 4 points at T4 and T5 were evaluated. Results Significant improvements were found in VA, IOP, proptosis, CAS, and TRAb levels in the adult group, and proptosis in the pediatric group at T5 (P <.05). Additionally, significant improvements were identified in TRAb levels and CAS (active GO at T0) in the pediatric group at T4 (P <.05). In the adult and pediatric group with active GO at T5, 71.4% and 60% experienced a decrease in CAS by ≥ 2 points, respectively; 89.3% and 60% achieved the response criterion of low activity disease (CAS < 4 points), respectively. Conclusion TCZ emerged as a valuable therapeutic option for Chinese patients with active, corticosteroid-resistant, moderate to severe GO. [ABSTRACT FROM AUTHOR]

Background and purpose Methods Results Conclusion Limited options exist for migraine prevention after stopping anti‐calcitonin gene‐related peptide monoclonal antibodies. A systematic review examining the benefits of switching between different classes (ligand vs. receptor monoclonal antibody) is essential, alongside well‐designed real‐world studies.In this cohort study 67 patients were included, who discontinued their first treatment with erenumab or fremanezumab. Patients (n = 31) switched to another monoclonal antibody class within 3 months, whilst those in the control group (n = 36) received standard care. Allocation to either group relied largely on the availability of alternative monoclonal antibody treatments, introducing pseudo‐random allocation. Changes in monthly migraine days were compared between groups 3 months post‐discontinuation of the first monoclonal antibody or initiation of a different monoclonal antibody class. A multivariate regression model was conducted that accounted for potential confounding factors.The groups were comparable at baseline and poor treatment response was the main reason for treatment discontinuation of the first monoclonal antibody. The switching cohort experienced a reduction of 3.9 monthly migraine days (95% confidence interval −6.4, −1.3, p = 0.004) compared with the control group.Transitioning to a different anti‐calcitonin gene‐related peptide monoclonal class yields reduction in monthly migraine days compared to returning to standard care for patients with inadequate initial treatment response. [ABSTRACT FROM AUTHOR]

Angiotensin II type-1 receptor antibody (AT1R-Ab) has been mooted as a potential effector of both acute and chronic antibody mediated rejection (AMR). A growing body of literature on the topic is now coming under scrutiny in the context of the evolving Banff AMR diagnostic classification system and refinement of recommendations for histocompatibility testing by the Sensitization in Transplantation Assessment of Risk (STAR) workgroup. This mini-review discusses the latest understanding of pathophysiological mechanisms, clinical evidence for the pathogenicity of AT1R-Ab, and methods of laboratory testing. [ABSTRACT FROM AUTHOR]

Autoimmune encephalitis is a group of disorders characterized by symptoms of dysfunction of the limbic and extra‐limbic systems that occur in association with antibodies against intracellular antigens, synapses, or proteins located on the surface of nerve cells. Anti‐NMDA (N‐methyl‐D‐aspartate) receptor encephalitis was first described in 2007 and has become one of the most commonly recognized autoimmune encephalitides. The disease is predominantly female (81%) and affects young patients (37% <18 years old, 95% <45 years old), with up to 58% of women over 18 years old having ovarian teratoma. Clinical symptoms of anti‐NMDA receptor encephalitis include psychiatric disorders (anxiety, agitation, bizarre behavior, hallucinations, delusions, and memory impairment); seizures and epileptic states; and other neurologic symptoms (muscle tone abnormalities, eye movement disorders, and central ventilatory disorders). Diagnosis of this condition can be difficult due to the non‐specific nature of the symptoms, often leading to delays in appropriate treatment. Early diagnosis and timely treatment of anti‐NMDA receptor encephalitis, especially in young women with ovarian teratoma, has significantly improved the chances of full recovery and improved reproductive health outcomes for patients. [ABSTRACT FROM AUTHOR]

Liver dysfunction can occur in patients presenting with thyrotoxicosis, due to several different aetiologies. A 42-year-old man had mild liver dysfunction on presentation with hyperthyroidism due to Graves' disease (GD): ALT 65 (0–45 IU/L), fT4 41.2 (9–23 pmol/L), fT3 > 30.7 (2.4–6 pmol/L), and TSH < 0.01 (0.3–4.2 mIU/L). His liver dysfunction worsened following the initiation of the antithyroid drug (ATD) carbimazole (CBZ), with ALT reaching a zenith of 263 IU/L at 8 weeks following presentation. Consequently, CBZ was stopped, and he was managed with urgent radioiodine therapy. His liver function tests (LFTs) improved within 1 week of stopping carbimazole (ALT 74 IU/L). Thionamide-induced liver dysfunction is more typically associated with a 'cholestatic' pattern, although he had a 'hepatitic' pattern of liver dysfunction. The risk of liver dysfunction in GD increases with older age and higher titres of thyroid-stimulating hormone receptor antibody (TRAb). This review of the literature seeks to explore the possible causes of liver dysfunction in a patient presenting with hyperthyroidism, including thyrotoxicosis-induced liver dysfunction, ATD-related liver dysfunction, and the exacerbation of underlying unrelated liver disease. [ABSTRACT FROM AUTHOR]

Background: Human adenovirus type 7 (HAdV7) has become a major public health threat due to its widespread transmission, severe associated pneumonia, and a lack of effective anti-HAdV7 drugs. The aim of the current study is to design a humanized monoclonal antibody (mAb) demonstrating efficacy against HAdV-7 infections in vitro and in vivo. Methods: The humanized neutralizing antibody, 3G5-hu, was derived from the murine mAb 3G5. Antibody activity was evaluated using a flow cytometry-based neutralization (FCN) assay to identify humanized mAbs retaining potent neutralizing activity. Additionally, a humanized hDSG2/hCD46 dual-receptor transgenic mouse model was developed to simulate HAdV-7 infection. Results: Using recombinant HAdV-7 expressing enhanced green fluorescent protein and clinically isolated wild-type HAdV-7, the half-maximal effective concentration of 3G5-hu against HAdV-7 was determined to be < 30 ng/mL. Notably, 3G5-hu exhibits high specificity for the hexon protein of the HAdV-7 capsid (affinity: KD = 9.02 × 10− 11 M). Microneutralization studies with wild-type HAdV-7 and rAd7EGFP confirmed that humanized mAb 3G5-hu neutralizes 10–30 ng/mL HAdV-7 (approximately 67–200 pM). Furthermore, hDSG2/hCD46 double-receptor transgenic mice are more susceptible to HAdV-7 infection than single-receptor transgenic mice. Meanwhile, the humanized mAb 3G5-hu provides good protection against HAdV-7 infection in hDSG2/hCD46 knock-in transgenic mice. Conclusions: The newly designed humanized mAb 3G5-hu specifically neutralizes HAdV-7 in vitro and in vivo. 3G5-hu elicits protection against HAdV-7 infection in hDSG2/hCD46 knock-in transgenic mice. The findings of this study provide insights to guide the future development of preventative and therapeutic treatments for HAdV-7 infection. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICIs) combined with chemotherapy have improved overall survival in patients with small-cell lung cancer, but have also led to an increase in adverse effects. The incidence of ICI-induced paraneoplastic neurological syndrome (PNS) is relatively low when the primary lung lesion is well controlled. However, it is associated with high mortality and disability rates. In this report, we present two cases of extensive-stage small-cell lung cancer with neurological symptoms and positive paraneoplastic antibodies in the serum and cerebrospinal fluid (CSF) following ICI therapy. Although the symptoms improved after treatment with systemic high-dose immunoglobulin and glucocorticoids, one patient, unfortunately, succumbed to tumor progression four months later, whereas the other patient experienced persistent difficulty in standing and walking despite improved muscle strength. In cases where neurological symptoms that cannot be explained by tumor metastases arise during ICI treatment, paraneoplastic syndromes should be considered and testing for antineuronal antibodies is crucial, as early detection and intervention can help mitigate their impact. Further research is needed to develop better predictive strategies and treatment protocols for these adverse reactions. [ABSTRACT FROM AUTHOR]

Background: Thyroid-blocking immunoglobulins (TBI) are present in 10%–15% of patients with autoimmune thyroid disease (AITD). TBI affect thyroid function. The analytical performance of a novel TBI bioassay was evaluated. Methods: Sera from AITD patients were tested with a cell-based TBI reporter bioassay (Thyretain®) with the expression of a luciferase transgene as readout and a new "Turbo™" TBI bioassay with a readout based on a cyclic AMP-activated luciferase. All samples were also run on two TSH-R binding immunoassays. A Passing–Bablok regression, a Bland–Altman plot, and user/lot comparisons were performed. In addition, dose–response curves for Turbo and Thyretain were fitted using serial dilutions, and half-maximal and 80% inhibitory concentrations (IC50/IC80) were compared. Results: Of 1,011 unselected AITD patients, 131 patients (212 samples) were TBI positive. Of the 212 samples, 149 (70.3%), 47 (22%), and 16 (7.5%) were hypothyroid, euthyroid, and hyperthyroid, respectively. The three thyrotropin receptor antibody (TSH-R-Ab) assays were negative in 90 controls devoid of autoimmune thyroid disorders. In contrast, the Turbo cyclic adenosine 3′,5′-monophosphate (cAMP) TBI, Thyretain TBI, and the binding assays detected TBI in 212 (100%), 168 (79%), and 138/180 (65%) samples, respectively (p < 0.001). Turbo highly correlated with thyroid function (p < 0.001). The percentage inhibition in both Turbo and Thyretain correlated with TSH-R-Ab binding assay positivity (both p < 0.001). The two bioassays correlated (r = 0.8, p < 0.001), and the Bland–Altman plot displayed no significant bias (0.24). Values scatter with slight systemic deviation between TBI mean values of 10%–50% inhibition, with higher Turbo than Thyretain results. Intra-assay validation demonstrated adequate precision with a very low coefficient of variation (average CV 5.4%) and lower CV with samples with a high inhibitory effect (CVAverage= 1.7% for a sample with 95% inhibition Thyretain). CV did not differ between users (p = 0.35) and lots (p = 0.121). The IC50/IC80 values were 1.55 ng/mL/3.48 ng/mL for Turbo and 6.76 ng/mL/18.46 ng/mL for Thyretain, respectively, demonstrating the markedly higher sensitivity of Turbo. Conclusions: The novel, easy-to-perform, rapid, and reliable Turbo TSH-R blocking bioassay detected significantly more TBI than the established immunoassays, emphasizing its higher analytical performance and clinical utility in the management of patients with AITD. [ABSTRACT FROM AUTHOR]

Macrophages measure the "eat-me" signal immunoglobulin G (IgG) to identify targets for phagocytosis. We tested whether prior encounters with IgG influence macrophage appetite. IgG is recognized by the Fc receptor. To temporally control Fc receptor activation, we engineered an Fc receptor that is activated by the light-induced oligomerization of Cry2, triggering phagocytosis. Using this tool, we demonstrate that subthreshold Fc receptor activation primes mouse bone-marrow-derived macrophages to be more sensitive to IgG in future encounters. Macrophages that have previously experienced subthreshold Fc receptor activation eat more IgG-bound human cancer cells. Increased phagocytosis occurs by two discrete mechanisms—a short- and long-term priming. Long-term priming requires new protein synthesis and Erk activity. Short-term priming does not require new protein synthesis and correlates with an increase in Fc receptor mobility. Our work demonstrates that IgG primes macrophages for increased phagocytosis, suggesting that therapeutic antibodies may become more effective after initial priming doses. [Display omitted] • Oligomerization of FcR-ITAM domains is sufficient to trigger phagocytosis • Prior subthreshold activation of FcRs enhances antibody-dependent phagocytosis • FcR activation increases FcR mobility within 1 h • FcR activation increases phagocytosis for days by changing gene expression via Erk Bond et al. use optogenetics to show that prior subthreshold Fc receptor activation increases the phagocytosis of future antibody-opsonized targets. This priming response lasts at least 72 h and is associated with increased FcR mobility in the short term and Erk-mediated transcriptional changes in the long term. [ABSTRACT FROM AUTHOR]

Purpose: To comparatively analyze the clinical characteristics of patients with ocular myasthenia gravis (OMG) referred to an ophthalmology clinic, according to anti-acetylcholine receptor antibody (AchR Ab)-seropositivity. Study design: Retrospective Cohort Study. Methods: Medical records of patients with OMG who presented to a tertiary eye care center between 2003 and 2020 were retrospectively reviewed. Demographics, ophthalmologic characteristics, response to medical treatment, presence of autoimmune thyroid disease and thyroid autoantibody were compared between the AchR Ab seropositive and seronegative groups. Results: A total of 130 patients with OMG were identified; among them, 46 patients (35.4%) had autoantibody against acetylcholine receptors. The mean age at symptom onset was 42.4 ± 18.9 years. There were no differences in mean age at symptom onset, gender ratio, and mean follow-up period between patients with seropositive and seronegative OMG. Graves ophthalmopathy was significantly more frequent in seronegative patients (p = 0.04), while thymic disease (p < 0.01) was more frequent in seropositive patients (p < 0.01). Among patients with seropositive OMG, 52.3% showed a good response to medical treatment, while only 31.4% of the seronegative patients were classified as good responders (p = 0.01). Thyroid dysfunction was found in 27.4% patients with OMG and the proportion of thyroid dysfunction was not different according to anti-acetylcholine receptor antibody-seropositivity. Conclusion: Seropositivity to acetylcholine receptor antibody is associated with a better response to medical treatment and lower risk of concomitant autoimmune thyroid disease in patients with OMG. [ABSTRACT FROM AUTHOR]

Summary: Antibodies have multiple biological activities. They can both recognize and act on specific antigens. They can protect against and cause serious diseases, enhance and inhibit antibody responses, enable survival, and threaten life. Which among their many, often antagonistic properties explains that antibodies were selected half a billion years ago and transmitted to mammals across millions of generations? In other words, what is the function of antibodies? Here I examine how their structure endows antibodies with unique cognitive and effector properties that contribute to their multiple biological activities. I show that rather than specific properties, antibodies have large functional repertoires. They have a cognitive repertoire and an effector repertoire that are selected from larger available repertoires, themselves drawn at random from even larger virtual repertoires. These virtual repertoires provide the adaptive immune system with immense, constantly renewed, reservoirs of cognitive and effector functions that can be actualized at any time according to the context. I propose that such a flexibility, which enables living individuals to adapt to a rapidly changing environment, and even deal with an unknown future, may provide a better selective advantage than any particular function. [ABSTRACT FROM AUTHOR]

Summary: Fc gamma receptors (FcγRs) are a family of receptors that bind IgG antibodies and interface at the junction of humoral and innate immunity. Precise regulation of receptor expression provides the necessary balance to achieve healthy immune homeostasis by establishing an appropriate immune threshold to limit autoimmunity but respond effectively to infection. The underlying genetics of the FCGR gene family are central to achieving this immune threshold by regulating affinity for IgG, signaling efficacy, and receptor expression. The FCGR gene locus was duplicated during evolution, retaining very high homology and resulting in a genomic region that is technically difficult to study. Here, we review the recent evolution of the gene family in mammals, its complexity and variation through copy number variation and single‐nucleotide polymorphism, and impact of these on disease incidence, resolution, and therapeutic antibody efficacy. We also discuss the progress and limitations of current approaches to study the region and emphasize how new genomics technologies will likely resolve much of the current confusion in the field. This will lead to definitive conclusions on the impact of genetic variation within the FCGR gene locus on immune function and disease. [ABSTRACT FROM AUTHOR]

Evidence has been accumulating that elements of the vertebrate pituitary adenylate cyclase-activating polypeptide (PACAP) system are missing in non-chordate genomes, which is at odds with the partial sequence-, immunohistochemical-, and physiological data in the literature. Multilevel experiments were performed on the great pond snail (Lymnaea stagnalis) to explore the role of PACAP in invertebrates. Screening of neuronal transcriptome and genome data did not reveal homologs to the elements of vertebrate PACAP system. Despite this, immunohistochemical investigations with an anti-human PAC1 receptor antibody yielded a positive signal in the neuronal elements in the heart. Although Western blotting of proteins extracted from the nervous system found a relevant band for PACAP-38, immunoprecipitation and mass spectrometric analyses revealed no corresponding peptide fragments. Similarly to the effects reported in vertebrates, PACAP-38 significantly increased cAMP synthesis in the heart and had a positive ionotropic effect on heart preparations. Moreover, it significantly modulated the effects of serotonin and acetylcholine. Homologs to members of Cluster B receptors, which have shared common evolutionary origin with the vertebrate PACAP receptors, PTHRs, and GCGRs, were identified and shown not to be expressed in the heart, which does not support a potential role in the mediation of PACAP-induced effects. Our findings support the notion that the PACAP system emerged after the protostome-deuterostome divergence. Using antibodies against vertebrate proteins is again highlighted to have little/no value in invertebrate studies. The physiological effects of vertebrate PACAP peptides in protostomes, no matter how similar they are to those in vertebrates, should be considered non-specific. [ABSTRACT FROM AUTHOR]

The aim of the study was to explore the clinical features related to early hypothyroidism and the relationship between the changes of thyrotropin receptor antibodies (TRAb) and early hypothyroidism in the course of131 I treatment for Graves' disease. This study was a retrospective observation, including 226 patients who received the first131 I treatment. The general information and laboratory tests were collected before and after131 I treatment, and the laboratory data affecting the difference in disease outcome were analyzed. According to the changes of antibodies in the third month, whether the changes of antibodies were involved in the occurrence of early-onset hypothyroidism was analyzed. Early onset hypothyroidism occurred in 165 of 226 patients, and the results showed that the incidence of early hypothyroidism was higher in patients with low baseline TRAb level (p=0.03) and increased TRAb after treatment (p=0.007). Both baseline TRAb levels (p<0.001) and the 24-hour iodine uptake rate (p=0.004) are significant factors influencing the changes in TRAb. The likelihood of a rise in TRAb was higher when the baseline TRAb was less than 18.55 U/l and the 24-hour iodine uptake level exceeded 63.61%. Low baseline and elevated post-treatment levels of TRAb were significantly associated with early-onset hypothyroidism after131 I treatment. Monitoring this index during RAI treatment is helpful in identifying early-onset hypothyroidism and mastering the clinical outcome and prognosis of Graves' disease. [ABSTRACT FROM AUTHOR]

Background: To evaluate the benefit-risk assessment of atogepant and calcitonin gene–related peptide (CGRP) monoclonal antibodies (mAbs) vs. placebo based on the number needed to treat (NNT) and the number needed to harm (NNH) in a blended episodic migraine and chronic migraine (EM + CM) population. Methods: The NNT was calculated based on achievement of a ≥ 50% reduction in mean monthly migraine days (MMDs) from baseline across 12 weeks. The NNH was calculated using the proportion of participants reporting a discontinuation due to adverse events (AEs). The primary analysis included data from studies of atogepant, erenumab, galcanezumab, eptinezumab and fremanezumab. Results: In the primary analysis, the calculated NNT for atogepant 60 mg vs. placebo was 4.2 (95% credible interval (CrI) = 3.1–6.7), which was the lowest relative to the CGRP mAbs in the blended EM + CM population. Participants who received atogepant 60 mg or fremanezumab showed the most favorable NNH values (−1010 (95% Crl = 44 to ∞ to number needed to benefit 80) for atogepant) resulting from lower rates of discontinuation due to AEs compared with those receiving placebo. Conclusions: Atogepant demonstrated a favorable benefit-risk profile, with NNT and NNH values comparable (not statistically significant) with those of CGRP mAbs across all analyses. [ABSTRACT FROM AUTHOR]

Adaptive immune receptors, such as antibodies and T-cell receptors, recognize foreign threats with exquisite specificity. A major challenge in adaptive immunology is discovering the rules governing immune receptor–antigen binding in order to predict the antigen binding status of previously unseen immune receptors. Many studies assume that the antigen binding status of an immune receptor may be determined by the presence of a short motif in the complementarity determining region 3 (CDR3), disregarding other amino acids. To test this assumption, we present a method to discover short motifs which show high precision in predicting antigen binding and generalize well to unseen simulated and experimental data. Our analysis of a mutagenesis-based antibody dataset reveals 11 336 position-specific, mostly gapped motifs of 3–5 amino acids that retain high precision on independently generated experimental data. Using a subset of only 178 motifs, a simple classifier was made that on the independently generated dataset outperformed a deep learning model proposed specifically for such datasets. In conclusion, our findings support the notion that for some antibodies, antigen binding may be largely determined by a short CDR3 motif. As more experimental data emerge, our methodology could serve as a foundation for in-depth investigations into antigen binding signals. [ABSTRACT FROM AUTHOR]

Context Over the past several decades, there have been indications of potential shifts in the diagnostic strategies, treatment, and monitoring of patients with Graves disease (GD). Objective To evaluate current practices in managing GD and compare them to previous surveys Methods We used a global online survey of endocrinologists to assess shifts in the diagnosis, monitoring, and treatment in a typical patient with GD, as well as treatment variation in 5 different clinical scenarios. Results A total of 1252 respondents from 85 countries completed the survey. Methods used to diagnose an uncomplicated GD case have changed over the past decade, reflecting increased use of thyrotropin receptor antibody (TRAb) and reciprocal decreases in nuclear medicine studies. The preferred mode of therapy for uncomplicated GD was antithyroid drugs (ATDs) by 91.5% of respondents, radioactive iodine (RAI) therapy by 7%, and thyroidectomy by 1.5%. Compared with previous surveys, the use of RAI as a first-line choice decreased in all geographic regions. The United States had the sharpest decline in the selection of initial therapy with RAI, decreasing from 69% in 1990 to 11.1% in 2023. In patients with persistent TRAb positivity after 18 months, 68.7% of respondents would continue the use of ATDs. After a relapse of GD, resumption of ATDs was selected by 59.9% of respondents. In patients with active thyroid eye disease or planning pregnancy, ATDs were the first choice (67.5% and 72.8%, respectively), and thyroidectomy emerged as the second choice (22.9% and 15.6%, respectively). Conclusion Paradigm shifts have occurred in the management of uncomplicated GD and its variants, as well as the response to persistent and recurrent hyperthyroidism. [ABSTRACT FROM AUTHOR]

Background: Generalized pustular psoriasis (GPP) is a rare, severe, and potentially life-threatening inflammatory cutaneous disease. IL-36 is a key treatment target in GPP. Spesolimab, a humanized monoclonal antibody of the IL-36 receptor, has demonstrated a good efficacy and a favorable safety profile in adults with GPP. However, data on its use in children are scarce. Methods: We treated patients aged 4– 12 years with GPP with a single dose of spesolimab. The Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) total score, GPPGA pustulation sub-score, Generalized Pustular Psoriasis Area and Severity Index (GPPASI), and the Japanese Dermatological Association severity index for GPP were evaluated. The levels of IL-36α, IL-36β, and IL-36γ were detected by the magnetic bead-based immunoassays, and the levels of IL-17A, IL-17C, IFN-γ, TNF, IL-6, and IL-8 were measured by the Olink proximity extension assay technology. Results: We included five patients (four boys and one girl) with a median age was 6.9 years old (range: 4.8 to 10.6 years), and a median age of onset of 1.7 years (range: 3 months– 10 years and 5 months). After 1 week of spesolimab administration, all patients had a total GPPGA score of 0/1 and pustulation subscore of 0, all patients had a GPPASI of 50, and four patients had a GPPASI of 75. Meanwhile, plasma levels of IL-36α, IL-36β, IL-36γ, IL-17A, IL-17C, IFN-γ, TNF, IL-6, IL-8 all decreased, and those of IL-36α, IL-36β, IL-17A, IL-17C, and IL-6 were statistically significant. There was no recurrence after 2 to 8 months of treatment. No other adverse event was recorded apart from one patient who experienced an upper respiratory infection in the first week. Conclusion: Spesolimab might be a prospective option for children aged 4 to 12 years. [ABSTRACT FROM AUTHOR]

Background: For the selective detection of thyroid-stimulating hormone receptor antibodies with stimulating properties (thyroid-stimulating immunoglobulins; TSI), a novel and rapid bioassay (Turbo TSI) has been introduced. We evaluate the clinical performance of Turbo TSI in Graves’ orbitopathy (GO) patients and compare it to a bridge-based TSI binding immunoassay and third generation TSH-R-binding inhibitory immunoglobulins (TBII) assay. Also, we investigate the association of Turbo TSI and TBII measurements with GO activity and severity, as well as response to intravenous methylprednisolone (IVMP), and compare results to previous findings on the bridge-based TSI binding immunoassay. Methods: Turbo TSI, TBII and bridge-based TSI binding immunoassay measurements were performed in biobank serum from 111 GO patients and control cases (healthy controls [HC; n=47], primary Sjögren’s disease [SD; n=10], systemic sclerosis [SSc; n= 10], systemic lupus erythematosus [SLE; n=10]). Clinical characteristics and response to treatment were retrospectively retrieved from GO patient files. Results: Turbo TSI had the highest sensitivity (97.3%) and negative predictive value (96.1%), while bridge-based TSI binding immunoassay showed the highest specificity (100%) and positive predictive value (100%). Differentiating GO patients from control cases, receiver operating characteristic (ROC) analysis showed an area under the curve (AUC) of 98.5%, 95.7% and 99.8% for Turbo TSI, TBII and bridge-based TSI binding immunoassay, respectively. Turbo TSI (p<0.001) and TBII (p<0.01) levels were higher in patients with active compared to inactive GO. Correlation with CAS was stronger for Turbo TSI (r=0.42) than TBII (r=0.25). No statistically significant differences were observed in IVMP responders vs. non-responders for Turbo TSI (p=0.092) and TBII (p=0.21). For identifying active GO, an AUC of 75% with Turbo TSI and 67% with TBII was found. For IVMP response, AUC was 66.3% with Turbo TSI and 62.1% with TBII. In multivariate logistic regression analyses, both assays were independently associated with disease activity (p<0.01 for both assays) and IVMP response (p<0.01 for Turbo TSI; p<0.05 for TBII). Conclusions: The new Turbo TSI functional bioassay has good clinical performance. Although turbo TSI is a stronger marker of activity and IVMP response than TBII, results are comparable to our previously published findings on the bridge-based TSI binding immunoassay. [ABSTRACT FROM AUTHOR]

Introduction: The presence of oligoclonal bands (OCBs) in cerebrospinal fluid (CSF) is a pivotal diagnostic marker for multiple sclerosis (MS). These bands play a crucial role in the diagnosis and understanding of a wide array of immune diseases. In this study, we explore the relationship between the cognitive profile of autoimmune encephalitis (AIE) and the presence of OCBs in CSF, with a particular emphasis on NMDA receptor antibodies. Methods: We studied a cohort of 21 patients across five tertiary centers, segregated into two distinct categories. One group comprised individuals who tested positive only for autoimmune encephalitis antibodies indicative of encephalitis, while the other group included patients whose CSF was positive for both autoimmune encephalitis antibodies and OCBs. Our investigation focused primarily on cognitive functions and behavioral alterations, supplemented by auxiliary diagnostic assessments such as CSF cell count, magnetic resonance imaging (MRI), and electroencephalogram (EEG) results, evaluated for the two patient groups. To validate our findings, we employed statistical analyses such as Fisher’s exact test with Benjamini-Hochberg correction. Results: Our study included 21 patients, comprising 14 who were presented with only autoimmune encephalitis antibodies, and 7 who were dual-positive. Among these patients, we focused on those with NMDA receptor antibodies. Of these, five were dual positive, and nine were positive only for NMDA receptor antibodies. The dual-positive NMDA group, with an average age of 27 ± 16.47 years, exhibited significantly higher CSF cell counts (p=0.0487) and more pronounced language and attention deficits (p= 0.0264). MRI and EEG results did not differ significantly between the groups. Conclusions: Our results point to OCBs as an additional marker of disease severity in AIE, especially in NMDA receptor-antibody positive patients, possibly indicating a broader inflammatory process, as reflected in elevated CSF lymphocytes. Regular testing for OCBs in cases of suspected AIE may aid in disease prognosis and identification of patients more prone to language and attention disorders, improving diagnosis and targeting treatment for these cognitive aspects. [ABSTRACT FROM AUTHOR]