Intravenous Immunoglobulin Research Articles (Page 1)

Kawasaki disease shock syndrome (KDSS) is a rare but severe complication of Kawasaki disease, often associated with intravenous immunoglobulin resistance, myocardial dysfunction, and higher risk of coronary complications. Leukemoid reaction is extremely uncommon in KDSS and can mimic hematologic malignancy, complicating timely diagnosis and management. A 4-year-7-month-old boy presented with fever, cervical lymphadenopathy, rash, and hypotension. Laboratory findings showed extreme leukocytosis (peak white blood cell 71.10 × 109/L), initially raising concern for acute leukemia. The patient was diagnosed with KDSS based on fever, mucocutaneous features, circulatory collapse, multi-organ involvement, and echocardiographic findings. Bone marrow aspiration confirmed reactive hyperplasia without blasts, and additional workup excluded hematologic malignancy. The child received intravenous immunoglobulin as first-line therapy but remained resistant. High-dose methylprednisolone was initiated, followed by tapering corticosteroids and low-dose aspirin. Short-term anticoagulation with dipyridamole and low-molecular-weight heparin was introduced as thromboprophylaxis, given the extreme inflammatory burden, hypoalbuminemia, serosal effusions, and elevated coagulation markers. Supportive therapy included albumin infusion, oxygen, and gastric protection. The patient showed rapid resolution of fever and shock after corticosteroid therapy, with progressive normalization of white blood cell and C-reactive protein levels. He was discharged in stable condition. At 1- and 24-month follow-up, laboratory results remained normal, and echocardiography confirmed absence of coronary artery aneurysms or ventricular dysfunction. This case emphasizes that KDSS with leukemoid reaction may mimic hematologic malignancy, delaying appropriate immunomodulatory therapy. Extreme leukocytosis (≥70 × 109/L) should not exclude KDSS, especially in children with unexplained fever and shock. Early recognition, adjunctive corticosteroid therapy, and individualized anticoagulation strategies are critical to prevent misdiagnosis and improve outcomes.

Talquetamab is a first-in-class GPRC5DxCD3 bispecific antibody approved for heavily pretreated relapsed/refractory multiple myeloma (RRMM), and this multicenter retrospective analysis of 114 RRMM patients treated between October 2023 and January 2025 demonstrated significant efficacy in a heavily pretreated population with median 6 prior therapies. All patients were triple-class refractory, 79% were penta-refractory, and 65% had received prior BCMA-targeted therapy. The overall response rate was 73%, including complete response in 26% and very good partial response in 26%, with six-month progression-free and overall survival rates of 56 and 86% respectively and median progression-free survival of 10 months. Common adverse events included cytokine release syndrome (CRS; 54% with grade ≥2 in 7.3%), infections (27%), and immune effector cell-associated neurotoxicity syndrome (9.8%). The 3-month cumulative infection incidence of 14% for both bacterial and viral infections, where 59% were viral and 41% bacterial, grade ≥3 infections occurred in 18%, and intravenous immunoglobulin was used in 61% of patients. Significant weight loss was observed, with a mean 8.8% decrease at 6 months. This real-world analysis confirms talquetamab's efficacy in heavily pretreated RRMM while highlighting notable toxicities, including progressive weight loss and infections, which require rigorous monitoring and proactive supportive care.

Background Autoimmune Hemolytic anemia (AIHA) a relatively uncommon form of hemolytic anemia, which is characterized by the presence of autoantibodies directed against erythrocyte surface antigens, most frequently of the IgG isotype. A positive Direct Antiglobulin Test (DAT) is a key diagnostic criterion for AIHA. However, when hemolysis involves multiple autoantibodies, the standard DAT (polyspecific, anti-IgG + C3) may fail to detect certain antibodies, potentially delaying appropriate treatment. Cases presentation We reported one patient with severe AIHA mediated by IgG and IgA autoantibodies was successfully treated with Multi-drug combination regimens. A 58-year-old female was admitted to the hospital presenting with a history of fatigue, jaundice and soy sauce-colored urine for one day. Upon admission, a complete blood count revealed a critically low hemoglobin level of 41 g/L and a life-threatening condition. Initially diagnosed with IgG-mediated AIHA via standard DAT, the patient showed suboptimal response to glucocorticoids, intravenous immunoglobulin (IVIG), and transfusion support. Subsequently, through the extended DAT (monospecific, anti-IgA, anti-IgG, anti-IgM, and anti-C3) test results, the patient was diagnosed as severe AIHA mediated by IgG and IgA. Based on extended DAT results, the treatment plan was modified to include combination therapy with dexamethasone, rituximab, cyclosporine, and bortezomib, alongside intensified plasma exchange. Conclusions The extended DAT testing is recommended for all patients with clinical and laboratory evidence of acute hemolysis. Early detection helps in avoiding further investigations and provide efficient management. Severe AIHA mediated by multiple autoantibodies requires early intensive combination therapy, including immunosuppressive agents, IVIG and plasma exchange.

Intravenous immunoglobulin (IVIG) administered at high doses is used to treat a wide array of autoimmune diseases. Studies in murine models have identified that the anti-inflammatory activity of IVIG is dependent on sialylation of the N-linked glycan on the CH2 domain of immunoglobulin G (IgG), the type I IgG inhibitory Fc receptor FcγRIIB, and the type II Fc receptor dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN). We hypothesized that DC-SIGN, a C-type lectin, may directly interact with glycans on FcγRIIB, augmenting its ability to bind sialylated IgG. We found that Fc-engineering sialylated IgG1 to enhance its affinity for FcγRIIB resulted in a molecule that was more potent than IVIG in reducing the inflammatory sequelae of antibody or T cell-mediated autoimmune diseases, providing the basis for a class of potent anti-inflammatory therapeutics.

Background: Blood and blood product transfusions are common among hospitalized neonates in this advanced era at NICU, particularly in those of preterm low birth neonates. Objective: In this study we try to find out the types of transfusion in a neonatal intensive care unit among the sick neonates. Methods: Neonates who required blood or blood product transfusion between 1st Jan 2022 to 31st March 2023 at the neonatal intensive care Unit (NICU) of Ad- Women’s Medical college Hospital were included in this prospective observational study. Total 86 inborn and out-born babies with regular maternal antenatal care (ANC) check up with ANC book and other papers with good documentation were selected for the study. A structured questionnaire was used to obtain medical data i.e maternal and neonatal medical problems, indications for blood or other types of transfusion, type of blood products transfused and the frequency of transfusion during the hospital stay. We also observed maternal illnesses during pregnancy and neonatal demography as well as illnesses during the time of admission. Written consent was obtained from the parents or caregiver each time of blood and blood product transfusion as well as for the inclusion in the study. Statistical analysis was done with computer software SPSS version 16 (Statistical Package for Social Sciences). All data were processed and analyzed. Analyzed data were presented in the form of tables, charts, and graphs with due interpretation. Results: Out of 743 neonates who were admitted during the study period, 86 (10.9%) were studied who required one or more episode of blood or blood product transfusion. Five (5.80%) neonates required whole blood for the double volume exchange transfusion. Neonates required packed red blood cell (PRBC) for anemia was in 40(46.51%), fresh frozen plasma (FFP) for abnormal coagulation profile (with/ without active bleeding) in 64 (74.41 %), platelet for thrombocytopenia in 44(51.16%),albumin for hypoalbuminemia in 23(26.73%) and intravenous immunoglobulin (IVIG) in 9(11%) for severe thrombocytopenia. Four types of transfusion FFP+ PRBC +Albumin+ PLT required in 7(8.10%) neonates, 3 types of transfusion FFP+ platelet+ PRBC in 11(12.79%), FFP+ PLT+albumin in 3(3.48%) neonates, 2 types of transfusion FFP+PRBC in 9(10.46%), FFP+ albumin in 6(6.90%), FFP+ Platelet in 10(11.62%). Single type of transfusion in the form of Platelet or PRBC or FFP or whole blood in 7(8.12%), 10(11.62%), 11(12.79%) and 5(5.80%) respectively. So multiple transfusions were required in 53(61.62%) neonates. Conclusion: In this study we found that the Fresh frozen plasma transfusion was highest and the IVIG was the lowest number of transfusions in a neonatal intensive care unit. Northern International Medical College Journal Vol. 15 No. 1-2 July 2023-January 2024, Page 672-677

ABSTRACT Myelin oligodendrocyte glycoprotein antibody-associated disease (MOG AD) is a rare autoimmune demyelinating condition typically presenting with optic neuritis, transverse myelitis, or encephalitis. Its occurrence in immunocompromised individuals, particularly those with human immunodeficiency virus (HIV), is rare and presents unique diagnostic and therapeutic challenges. We report the case of a 70-year-old HIV-positive man who developed alexia without agraphia following treatment for opportunistic infections, including Pneumocystis jirovecii pneumonia and cytomegalovirus. Brain MRI revealed a non-enhancing hyperintense lesion in the medial left occipital lobe extending into the splenium of the corpus callosum. MOG-IgG was positive at a titer of 1:30, while aquaporin-4 antibodies and paraneoplastic panels were negative. Neuropsychological assessment confirmed selective impairment in visual word recognition with preserved writing ability, consistent with alexia without agraphia. The patient was treated with intravenous immunoglobulin (IVIG) without corticosteroids due to immunosuppressive concerns and demonstrated approximately 40% improvement in visual word recognition accuracy. At six months follow-up, no relapse was observed, and reading ability remained stable. This case represents the first reported instance of MOGAD presenting with alexia without agraphia in an HIV-positive individual, underscoring the importance of considering autoimmune demyelination in immunosuppressed patients with focal neurological deficits.

Background Anti-metabotropic glutamate receptor 5 (mGluR5) encephalitis is a rare autoimmune disorder that targets the metabotropic glutamate receptor. It is frequently linked to limbic encephalitis and paraneoplastic syndromes, such as Ophelia syndrome associated with Hodgkin lymphoma. Due to its rarity, the complete clinical spectrum and regional variations of this condition, particularly among Chinese populations, remain inadequately understood. Case description We present a case of a 39-year-old Chinese male diagnosed with anti-mGluR5 encephalitis. The patient initially presented with persistent fever, which later progressed to seizures, psychosis, apathy, drowsiness, and memory impairment. Brain imaging findings were unremarkable, while electroencephalogram (EEG) revealed predominant beta wave activity. Cerebrospinal fluid (CSF) analysis showed pleocytosis and elevated protein levels. Both serum and CSF tested strongly positive for mGluR5 antibodies (titers 1:160 and 1:640, respectively), with no other autoantibodies detected. A thorough evaluation revealed no evidence of an underlying tumor. Symptom resolution was rapid following intravenous methylprednisolone pulses, with sustained remission achieved through rituximab therapy combined with a gradual tapering of steroids over one year of follow-up. Literature review In 18 Chinese patients, the median age was 36 years (range 7–60), with 61% being male (11/18). Only 17% (3/18) had associated tumors, including two cases of teratomas and one of gangliocytoma. The clinical manifestations were highly diverse, with headache (44.4%), irritability/sleepiness (38.9%), and seizures (38.9%) being the most prevalent symptoms. Additional symptoms included hallucinations (33.3%), fever (27.8%), memory impairment (27.8%), dystonia (22.2%), and consciousness disorders (22.2%). Antibody analysis showed that 94.4% (17/18) of patients were serum mGluR5-positive, 61.1% (11/18) had mGluR5 antibodies in cerebrospinal fluid, and 55.5% (10/18) tested positive in both. Magnetic resonance imaging (MRI) anomalies were identified in 72.2% of patients, typically affecting the temporal/insular lobes and deep gray matter. Immunotherapy, consisting of steroids, intravenous immunoglobulin and/or immunosuppressive drug, was administered to 94.4% (17/18) of patients, resulting in favorable outcomes for 17 cases. Conclusion This study highlights that anti-mGluR5 encephalitis in Chinese patients exhibits significant clinical heterogeneity and a notably low association with tumors (17%), contrasting with higher rates reported elsewhere. Both serum and CSF antibody testing are crucial for diagnosis. Immunotherapy, including steroids and potentially rituximab, appears highly effective. Clinicians should be aware of the broad symptom spectrum and the relatively low paraneoplastic risk in this population. Vigilance for tumors, especially teratomas and neural tumors, remains essential.

ABSTRACT Introduction: Kawasaki Disease (KD) and Multisystem Inflammatory Syndrome in Children (MIS-C) are two related conditions that primarily affect pediatric patients. The overlap in clinical symptoms, physical findings, and laboratory results between MIS-C and KD complicates diagnosis and treatment, as children with MIS-C may fulfill the criteria for KD. Early recognition of distinguishing clinical, laboratory, and echocardiographic findings is crucial for timely diagnosis and appropriate treatment, which can mitigate the risk of severe cardiovascular, gastrointestinal, and neurological complications. Objective: This study aims to compare the clinical profile, laboratory profile, 2-D echocardiographic findings, treatment, and outcome of children with KD vs MIS-C at a tertiary hospital in the Philippines. Method: A retrospective, analytic cohort study was done to differentiate the clinical profiles, laboratory profile, treatments, and outcomes of pediatric patients aged less than 19 years old, admitted with a diagnosis of KD, from January 2016 to December 2019 (pre-COVID-19 pandemic), and MIS-C cases admitted from January 2020 to December 2023, in a private, urban, tertiary hospital. Descriptive statistics (frequency and proportion, mean and standard deviation, median and inter-quartile range) were used to summarize the general and clinical characteristics of the participants. Independent T-test, Mann-Whitney U test and Fisher’s Exact/Chi-square test were used to determine the difference of mean, median and frequency of laboratory parameters among groups. Results: The study included 87 patients, with 60 categorized in the KD group (13 diagnosed with complete KD and 47 with incomplete KD) and 27 in the MIS-C group. MIS-C patients were more likely to be older (p = 0.023), present with GI symptoms such as vomiting (48.2% in MIS-C vs. 12.8% in KD) and abdominal pain (40.7% vs. 6.4%), respiratory symptoms such as shortness of breath (29.6% vs 0%) and wheezing (14.8% vs 0%), have lower WBC (6.30 in MIS-C vs. 13.07 in complete KD and 10.18 in incomplete KD, p < 0.001), ANC (5,940 in MIS-C vs. 13,660 in complete KD and 10,432 in incomplete KD, p = 0.002), and platelet count (280 in MIS-C vs. 368 in complete KD and 364 in incomplete KD, p = 0.13), and experience more complications such as myocarditis (14.81% vs. 0%), hypotension (18.52% vs. 0%), shock (14.81% vs. 0%), and pneumonia (40.74% vs. 17.02% for incomplete KD and 7.69% for complete KD). In contrast, key features of KD, including conjunctival injection (100% in KD vs. 25.9% in MIS-C), rash (100% vs 59.3%), oral changes (92.3% vs. 22.2%), and cervical lymphadenopathy (92.3% vs. 29.6%), elevated laboratory results of CRP (12.89 in MIS-C vs. 46.53 in complete KD and 111.15 in incomplete KD, p < 0.001), ESR (41.91 in MIS-C vs. 61.73 in complete KD and 82.49 in incomplete KD, p = 0.003), and AST/ALT ratios (0.42 in MIS-C vs. 1.88 in complete KD and 0.62 in incomplete KD, p = 0.034) were more frequently observed in KD patients. Combination therapy involving intravenous immunoglobulin (IVIG), methylprednisolone, and acetylsalicylic acid (ASA) was more common in MIS-C patients than in KD patients (48.15% in MIS-C vs. 7.69% for complete KD and 2.13% for incomplete KD), who mainly received IVIG and ASA alone (84.62% in complete KD and 93.62% in incomplete KD vs 3.7% in MIS-C). Conclusions: This study highlights key clinical and laboratory differences between MIS-C and KD in a private tertiary hospital setting. MIS-C patients were generally older, exhibited more GI and respiratory symptoms, and had a higher risk of serious complications. In contrast, KD cases more often presented with classic mucocutaneous signs and elevated inflammatory markers. These findings underscore the importance of early differentiation, as MIS-C often requires more intensive management. The study also identifies practical diagnostic indicators including CBC parameters such as WBC, ANC, and platelet count that may aid clinicians, particularly in resource-limited settings. Further multicenter research involving both public and private hospitals is needed to validate and enhance the diagnostic criteria.

The aims of this study were to determine the performance of a large language model (LLM) with a zero-shot strategy for the classification of several factors relevant to the consideration of intravenous immunoglobulin (IVIg) weaning. In many cases, IVIg should be weaned to prevent excessive resource utilisation and adverse effects. A cohort study was conducted examining neurology outpatients receiving regular IVIg in a 2-month period. Prespecified criteria were used to determine how many individuals were suitable for IVIg weaning. A LLM was applied to determine the level of performance with which the model could provide answers to the prespecified criteria. In the inclusion period, 14 individuals were identified and four patients fulfilled the criteria for possible IVIg weaning. The total annual cost saving with IVIg weaning was conservatively estimated to be $84702.20 (1433.9 g of IVIg annually). The LLM achieved an overall classification accuracy of 78.6% (11/14) when a rule-based approach was applied to the individual criteria that it extracted from notes. Further research is indicated to determine the frequency with which patients suitable for IVIg weaning are identified at other centres and the degree to which LLM may be able to assist with this process.

Human metapneumovirus (HMPV) is an emerging respiratory pathogen causing infections across various age groups, particularly among children, the elderly, and immuno-compromised individuals. The recent surge of cases reported in late 2024 and early 2025 across Asia, Europe, and North America highlights its re-emergence as a pathogen of global concern. Laboratory confirmation, particularly using reverse transcription-polymerase chain reaction, remains the gold standard for diagnosis, while antigen detection and serology have supplementary roles. No licensed antivirals or vaccines are currently available, and management remains largely supportive, although ribavirin and intravenous immune globulin have been trialled in select severe cases. Strengthened surveillance networks, including WHO influenza-like illness/severe acute respiratory infections monitoring and national programmes, are crucial for early detection and control. This review provides an overview of HMPV's virology, epidemiology, clinical manifestations, diagnostic methods, and management strategies, with emphasis on the recent global resurgence and the need for continued vigilance and research.

Background Tislelizumab, a humanized IgG4 anti-programmed cell death 1 (PD-1) monoclonal antibody approved in China in 2019 for advanced solid tumors such as esophageal cancer, functions by blocking the PD-1/PD-L1 pathway to reactivate anti-tumor immunity. Common adverse reactions include fever and rash; however, toxic epidermal necrolysis (TEN)—a rare, life-threatening drug hypersensitivity reaction—is reported in fewer than 0.1% of patients receiving PD-1 inhibitors, with limited real-world evidence specifically linking it to tislelizumab. Case presentation A 70-year-old male with esophageal squamous cell carcinoma received two cycles of neoadjuvant therapy (nab-paclitaxel, cisplatin, and tislelizumab 200 mg) followed by partial esophagectomy. On day 86 after the first tislelizumab infusion, he developed a diffuse rash progressing to skin exfoliation, vesiculation, and a positive Nikolsky sign, leading to a diagnosis of TEN. Upon admission, his SCORTEN was 3 (predicting 35% mortality) and ALDEN score was 5, indicating a probable association with tislelizumab. Management included intravenous methylprednisolone, immunoglobulin, topical treatments, and nutritional support. The patient achieved complete recovery two months after symptom onset. Conclusion This case illustrates that tislelizumab can induce TEN after a prolonged incubation period (86 days in this instance). It underscores the importance of vigilant monitoring of skin and mucous membranes during treatment, early recognition and intervention, and adequate glucocorticoid dosing in managing this serious immune-related adverse event, offering valuable clinical insight for oncologists.

Introduction: Acute necrotizing encephalopathy (ANE) is a rare but severe neurological condition, typically triggered by viral infections, including influenza. It is characterized by a dysregulated immune-inflammatory host response, leading to rapid neurological deterioration, including encephalopathy and multifocal brain lesions. Diagnosis and treatment are challenging, and the condition is associated with high morbidity and mortality. Case description: We report the case of a 48-year-old immunocompetent male who presented twice to the emergency department with fever and rapidly progressing altered consciousness, followed by generalized seizures. Neuroimaging revealed characteristic bilateral thalamic lesions and diffuse cerebral haemorrhage. Rapid diagnostic testing confirmed influenza A virus infection, leading to the diagnosis of influenza-associated acute necrotizing encephalopathy. Despite the initiation of antiviral therapy with oseltamivir, along with high-dose intravenous corticosteroids and immunoglobulins, the patient passed away due to severe neurological complications. Discussion: Adult-onset ANE is exceptionally rare, particularly in Western populations, and is associated with a fulminant clinical course. Common features include altered mental status and seizures, often progressing to severe outcomes despite treatment. Given its non-specific prodromal symptoms and rapid neurological decline, early recognition and prompt neuroimaging are essential for diagnosis and management. Increased awareness of this condition among clinicians may facilitate earlier intervention and potentially improve outcomes. Conclusion: The present case report highlights the fatal outcome of ANE as a rare complication of Influenza A infection in an immunocompetent adult.

Background: Acute myocarditis is defined as an inflammatory process consisting of multiple complex physiopathological processes. Due to its variability, the management of this condition has been a topic of debate. Our study aimed to evaluate the efficacy and safety of intravenous immunoglobulin (IVIg). Methods: We retrospectively collected data from patients admitted to a paediatric cardiology department from 2015 to 2020. Following the inclusion and exclusion criteria, a total of 68 patients diagnosed with acute myocarditis were selected and divided into two groups: treated with IVIg and untreated. We determined clinical and paraclinical parameters, such as symptom remission, normalisation of the ejection fraction at discharge, and cardiac marker evolution. Mixed-design analysis of variance and McNemar tests were performed to determine the statistical differences between groups. Results: In the treated group, 88.2% of the patients developed symptom remission at discharge vs. 50% in the untreated group, and 61.8% of the treated patients presented normalisation of the ejection fraction (EF) vs. 8.8% in the untreated group (p < 0.05). The evolution of cardiac markers did not statistically differ between the treated and untreated groups. Regarding safety, three treated patients presented mild, temporary side effects. Conclusions: Having found a statistically significant improvement in symptomatology and left ventricular EF, our study suggests the efficacy of IVIg in the treatment of acute myocarditis. Treatment with immunoglobulins was relatively safe, with only mild adverse reactions (fever and mild chest pain).

Background: Anti-MDA5 dermatomyositis is a rare subtype of idiopathic inflammatory myopathy with high mortality, often due to interstitial lung disease (ILD). Myocardial involvement, although rarer, can be life-threatening. Early diagnosis and management can significantly impact outcomes. Case: A 47-year-old male with supposed history of rheumatoid arthritis (RA) presented with shortness of breath and had a cardiac arrest in the ED. He was found to have an ejection fraction of 10-15%. Ischemic evaluation and genetic testing were negative. Dermatologic findings of the Gottron sign, heliotrope rash, shawl sign, and mechanic’s hands were noted along with crackles in his lungs. Inflammatory markers were elevated but creatine kinase (CK) and aldolase were normal. Rheumatoid factor, anti-CCP, and anti-Jo-1 antibodies were negative. Myositis panel revealed high positive MDA-5 antibodies. Lung biopsy revealed ILD and endomyocardial biopsy showed evidence of inflammation. He was treated with steroids and intravenous immunoglobulin with inotropic support. Decision-Making: Anti-MDA5 dermatomyositis is known to be associated with high mortality related to rapidly progressive ILD. In contrast, this patient’s course was dominated by myocardial disease. Cardiac involvement in clinically apparent in only 10-20% of patients, and myocardial inflammation can lead to complications with poor outcomes. Furthermore, the lack of classic weakness and normal CK and aldolase posed a diagnostic challenge. Early diagnosis and initiation of anti-inflammatory therapy is essential to mitigate the high mortality rates associated with this elusive disease. Conclusion: This case illustrates the diagnostic challenges of anti-MDA-5 positive dermatomyositis, highlighting heart failure as a rare presentation.

Introduction: Vasospastic angina (VSA) is caused by brief spasms of the main coronary artery and its major branches, resulting in varying degrees of luminal occlusion. Although vasodilator therapy is widely used and significantly alleviates VSA symptoms, it has not led to notable improvements in the prognosis of patients with VSA. Recent studies have suggested that inflammation plays a crucial role in VSA. This study aimed to evaluate the potential effectiveness of immunomodulatory therapy for improving patient prognosis. Research Questions/Hypothesis: Immunomodulatory therapy can improve the prognosis of patients with vasospastic angina Methods: A total of 71 VSA patients from three medical centers were selected and divided into traditional therapy and immunomodulatory therapy groups according to their in-hospital treatment to evaluate the effects of immunomodulatory therapy on clinical outcomes. The traditional therapy group received widely used treatments for VSA, including nitrate esters, CCBs, anti-platelet agents, statins and et al. The immunomodulatory therapy group was treated with glucocorticosteroids and/or IVIG, in addition to traditional therapy Results: Patients receiving immunomodulatory therapy, including corticosteroids and intravenous immunoglobulin, exhibited significantly superior overall free-outcome probability (90.5% vs. 63.5%, p=0.03) and a trend toward reduced death rates (0/20 vs. 3/51, p=0.27) compared to those receiving traditional therapy. High LDL levels, statin use, and immunomodulatory therapy were identified as protective factors for the occurrence of adverse outcomes. Elevated neutrophil counts and immunomodulatory therapy remained significant in the stepwise multi-cox model, with hazard ratio2.06 (95% confidence interval: 1.22 - 3.48, p =0.01) and 0.19 (95% confidence interval: 0.04 - 0.93, p =0.04), respectively. Subgroup analysis revealed that participants with a serious state, higher plasma cTnI and NT-proBNP levels exhibited a higher free-outcome probability when they received immunomodulatory therapy, in comparison with those received traditional therapy. Conclusion: This study indicates that immunomodulatory therapy effectively reduces the occurrence of adverse outcomes in patients with VSA, supporting the idea that myocarditis represents the main pathogenesis of VSA; therefore, it should be an indispensable approach for VSA.

Background: The early identification and prediction of intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD) patients remain essential for mitigating the incidence of coronary artery complications. This research aimed to construct and validate an interpretable prediction model for IVIG-resistant KD using machine learning (ML) approaches and convert it into an intuitive software application, explore the pathogenic contributors to IVIG-resistant in KD Methods: A multicenter design study aimed at constructing and validating predictive models. The derivation cohort consisted of 3,023 KD patients admitted to Children’s Hospital of Soochow University between January 2016 and December 2024, utilized for training and internal validation of the models. For external validation, a dataset comprising 1,626 KD patients from the Anhui Provincial Children's Hospital, the Affiliated Xuzhou Children's Hospital of Xuzhou Medical University, and Jiangsu Province (Suqian) Hospital, admitted between January 2020 and December 2024, was employed. Utilizing 33 clinical variables readily obtainable or assessable within 24 h of KD patient admission, twelve ML algorithms were applied to develop predictive models. Their discriminative capacities were evaluated based on the area under the receiver operating characteristic curve (AUC). SHapley Additive exPlanations (SHAP) were subsequently used to assess feature importance and interpret the final model. The ultimate model underwent external validation using the designated dataset. Results: Among the twelve ML algorithms, the extra trees (ET) model exhibited superior discriminative capacity. Upon dimensionality reduction based on the ranked importance of features, an interpretable ET model incorporating eight variables was finalized. It achieved AUC values of 0.865 in internal validation, 0.810 in the Anhui cohort (n = 654), 0.744 in the Xuzhou cohort (n = 546), and 0.785 in the Suqian cohort (n=408). Furthermore, the model has been implemented as an accessible web-based application, enhancing its feasibility in clinical settings. Conclusion: This investigation established a reliable and interpretable ML model capable of predicting IVIG-resistant KD with high accuracy. The interpretation of machine learning techniques by adopting the SHAP method has potential value in helping to start preventive intervention for children with IVIG-resistant KD patients at an early stage, providing strong support for clinical practice.

Juvenile myasthenia gravis (JMG) is an autoimmune disease of the neuromuscular junction that affects children and adolescents under 18 years of age and can pose life risk. The clinical characteristics in Brazilian children have been barely described. A descriptive and retrospective study was carried out on 2024 to outline the clinical profile of patients with JMG at a neuromuscular disease center in Rio de Janeiro. Among the 11 eligible patients, there was a predominance of females (72.7%), with initial clinical manifestations at 5 years old. The most commonly observed initial form of disease presentation was ocular (45,5%), followed by bulbar form (27,3%), myasthenic crisis (18,2%) and muscular form (9,1%). The most frequent signs and symptoms through follow-up were ptosis (100%), muscle weakness (54,5%), dysphagia (45,4%), dysphonia (18,1%) and facial paresis (18,1%). Patients with ocular-onset disease experienced no disease progression, remaining with strictly ocular symptoms. In contrast, those with bulbar-onset developed limb weakness, and the single muscular-onset case developed ocular involvement, as all patients did at some point. Most patients had positive anti-acetylcholine receptor antibodies (72,7%) and none had anti-Musk antibodies. All patients used a cholinesterase inhibitor and only one (9%) did not require associated corticosteroids for disease improvement. Six patients (54.5%) had never had a myasthenic crisis, while 5 patients (45.5%) had at least one. Among those who did, all responded to human immunoglobulin and corticosteroid pulse therapy. Approximately one third (36,3%) required other immunosuppressants to control exacerbations. The majority have a normal thymus (72,7%), with thymectomy indicated for only one patient. Asthma is the most prevalent autoimmune comorbidity (27,2%), as is anxiety as a neuropsychiatric comorbidity (27,2%). At our neuromuscular disease center in Brazil, our patient profile is very similar to the descriptions made so far of patients with JMG.

Background Sepsis, a life-threatening condition caused by a dysregulated host response to infection, remains a major cause of mortality worldwide. Identifying reliable biomarkers for prognosis and treatment is urgently needed. This study investigates the role of the Apoptosis Inhibitor of Macrophages (AIM), also known as CD5L, as a potential prognostic biomarker and therapeutic target in sepsis. Methods We measured free and total AIM concentrations in 90 septic patients enrolled in SepsisDataNet.NRW cohort (German Clinical Trial Registry No. DRKS00018871; http://www.sepsisdatanet.nrw ). Blood samples were collected on days 1, 4, and 8, and AIM levels were quantified using ELISA. Kaplan-Meier analysis and Cox regression were performed to assess the association between AIM levels and 30-day survival. Western blot analysis was performed to detect AIM in human serum IgM and in the IgM-enriched intravenous immunoglobulin IVIG preparation Pentaglobin ® . Results High total AIM concentrations (>85 ng/ml) were significantly associated with improved 30-day survival on day 1 (HR: 3.131, 95% CI: 1.629-6.019, p = 0.009), 4 (HR: 2.525, 95% CI: 1.198-5.322, p = 0.0042), and day 8 (HR: 2.317, 95% CI: 0.8565-6.266, p = 0.0457). Free AIM showed a significant association with survival only on day 8 (HR: 2.374, 95% CI: 0.8721-6.461, p = 0.0393). Conclusion Total AIM concentration is a significant predictor of a 30-day survival in sepsis, supporting its potential use as a prognostic biomarker. Our findings also suggest that AIM may serve as a valuable prognostic biomarker and a potential target for immune-modulating therapies, including IgM-enriched intravenous immunoglobulins (IVIGs).

Background Cavernous sinus tuberculosis is an extremely rare manifestation of central nervous system tuberculosis in children, with only two cases reported worldwide. It can mimic malignancy or other inflammatory conditions. Its occurrence in children with primary immunodeficiency, particularly major histocompatibility complex (MHC) class II deficiency, has not yet been described. Case report We report an 11-year-old girl with a history of recurrent infections and chronic otitis media. She presented with right orbital swelling, severe headaches, and exophthalmos. Imaging revealed an extensive mass in the sinonasal and orbital regions, extending to the skull base and cavernous sinus. A computed tomography-guided biopsy and histopathology, supported by PCR testing for Mycobacterium tuberculosis , confirmed extensive orbital and cervicofacial tuberculosis. An immunological evaluation and genetic analysis revealed familial MHC class II deficiency. The patient received anti-tuberculosis therapy [isoniazid, rifampin, pyrazinamide, and ethambutol (HRZE) followed by isoniazid and rifampin (HR)], leading to clinical and radiological improvement. She continues with intravenous immunoglobulin replacement therapy every 21 days while awaiting a bone marrow transplantation. Conclusions This case highlights the importance of considering tuberculosis in atypical cavernous sinus lesions in children, especially in endemic regions. Severe or unusual infections should prompt evaluation for underlying immunodeficiency.

The development of de novo donor-specific anti-HLA antibodies (dnDSA) after lung transplantation (LuTX) has been increasingly linked to the onset of antibody-mediated rejection (AMR), chronic lung allograft dysfunction (CLAD), and impaired long-term outcomes. However, the therapeutic impact of intravenous immunoglobulin (IVIG) therapy in patients with dnDSA remains unclear. We conducted a retrospective single-center study of LuTX recipients (2015–2019) who developed dnDSA post-transplantation and received IVIG-based therapy. Patients were classified as responders or non-responders based on post-treatment antibody clearance. Clinical, immunological and functional outcomes were compared. Among 47 patients with dnDSA and IVIG-based therapy, 23 (48.9%) achieved complete antibody elimination. Preemptive treatment, defined as initiation of IVIG therapy before onset of clinical symptoms, was found to be an independent predictor of antibody clearance (odds ratio 29.5; p = 0.013). Responders showed significantly lower baseline MFI. While differences in CLAD-free survival favored responders, they did not reach statistical significance. Preemptive IVIG therapy in asymptomatic dnDSA-positive LuTX recipients may enhance antibody clearance and reduce CLAD risk. These findings support early intervention strategies and underscore the need for prospective trials to define optimal therapeutic thresholds and timing.