BackgroundWhile immunoblobulin A(IgA) dominates gut mucosal immunity, the roles of immunoglobulin M (IgM) and immunoglobulin G (IgG) in host-microbiota interactions remain poorly characterized, particularly in schizophrenia (SCZ). Although gut dysbiosis and immune activation have been implicated in SCZ,the contribution of IgG/IgM-coated gut microbiota to disease associated inflammation and behavioral alterations remains unknown.MethodsWe recruited six patients with SCZ, six with other psychiatric disorders (OPD) and six age- and sex- matched healthy controls. IgG/IgM-coated gut microbiota were isolated from 100 mg fecal samples via magnetic-activated cell sorting (MACS) and profiled by 16S rRNA sequencing. A pilot an IgG/IgM-coated fecal microbiota transplantation (FMT) using anaerobically cultured human intestinal microbiota was conducted in mice to assess the effects on gut pathology, peripheral immunity, and behavior. The percentage of neutrophil granulocyte in peripheral blood was quantified microscopically, and statistical analyses were performed using one-way ANOVA in GraphPad Prism 8, with (p < 0.05.ResultsThe proportions of IgM-coated bacteria was significantly higher in patients with SCZ than in healthy controls (p<0.05), with enrichment of Rhodococcuss, Shigella, Clostridium and Streptococcus. Mice receiving a mixture of high-IgM-coated intestinal bacteria mixture showed reduced depletion of peripheral neutrophils, mild colon shortening, and mucosal inflammation compared with those receiving low IgM-coated or uncoated bacteria. In contrast, high IgG-coated bacteria, enriched in Rhodococcuss, Acinetobater and Pseudomonas, decreased in SCZ, but induced similar inflammatory gut changes. No IgG- nor IgM- induced anxiety-like behavior were detect in the mice.ConclusionsOur findings reveal that IgG/IgM-coated intestinal microbiota display distinct immunoreactive microbiota signatures associated with SCZ. These coated communities promote gut inflammation without inducing anxiety-like behavior, highlighting their potential as novel biomarkers of SCZ-associated immune dysregulation and as targets for personalized therapeutic strategies.

Since late 2019, the severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) pandemic has dramatically affected public health worldwide. Although systemic antibodies like Immunoglobulin G(IgG) and Immunoglobulin M (IgM)have been widely studied in Coronavirus disease 2019 (COVID-19), the role of Immunoglobulin A(IgA) in mucosal immunity remains less understood. This study evaluated whether salivary IgA levels could serve as prognostic markers for disease severity, progression, and outcomes in hospitalized patients with COVID-19. In this cross-sectional study, 61 hospitalized patients with COVID-19 were enrolled. After obtaining informed consent, saliva samples were collected at admission to measure IgA levels using an ELISA-based assay. Comprehensive clinical and laboratory data, including chest CT results, oxygen saturation, inflammatory markers, and clinical outcomes, were also recorded. Statistical tests were used to examine the association between salivary IgA levels and disease severity, progression, and outcomes. We enrolled 61 hospitalized patients with COVID-19 (30 females, 31 males; mean age: 56.20 ± 17.45 years; mean admission oxygen saturation: 89.98 ± 5.77%). At admission, 39.3% of patients reported dyspnea, and 40% demonstrated severe lung involvement on chest CT scans. The mean salivary IgA level was 1729.69 ± 391.35 mg/dL. No significant associations were found between salivary IgA levels and COVID-19 severity, disease progression, or clinical outcomes, including mortality. Our findings show that salivary IgA levels did not significantly correlate with COVID-19 severity, disease progression, or clinical outcomes in hospitalized patients. Therefore, salivary IgAalone cannot be recommended as a prognostic biomarker for COVID-19. Further research is needed to identify more reliable immunological indicators for predicting COVID-19 severity and outcomes.

Abstract Description Systemic lupus erythematosus (SLE) is an autoimmune disorder that affects multiple organs. Women show higher SLE incidence rate than men. Our preclinical studies showed that pro-inflammatory events initiated in the gut mucosa contribute to lupus autoimmunity. We also showed that the abundance and nuclear antigen (nAg) reactivity of IgA are higher in fecal samples from lupus-prone mice. Depletion of gut microbiota diminished the fecal IgA abundance and nAg reactivity. Therefore, we hypothesized that gut microbiota-IgA interaction contributes to systemic autoimmune progression and lupus pathogenesis. We tested this hypothesis by monitoring newly generated NZM2328-IgA-/- mouse model. We found that IgA deficiency, compared to wild-type (WT) mice, protects both male and female mice from severe nephritis. Paradoxically, dsDNA and nucleohistone reactive IgM and IgG antibody levels were significantly higher in NZM2328-IgA-/- mice. However, our preliminary observations suggest that expression levels of pro- and anti- inflammatory cytokines are comparable in WT and IgA-/- mice. Our ongoing studies are focused on understanding the role of gut microbiota in IgA-deficiency associated disease protection and the mechanisms by which IgA-gut microbiota interaction is contributing to autoimmunity. Overall, these systematic studies will, for the first time, address the role of IgA-gut microbiota interaction in lupus autoimmunity. Funding Sources NIH/NIAID R01AI138511 Topic Categories Mucosal and Regional Immunology (MUC)

Abstract Immunoglobulin G (IgG) plays a vital role in equine immunity, serving as the principal antibody involved in long-term immune protection and pathogen neutralization. Historically, the significance of IgG in horses was first recognized through studies of neonatal isoerythrolysis and failure of passive transfer (FPT) in foals, where inadequate ingestion or absorption of colostrum-derived IgG led to heightened morbidity and mortality. Early research emphasized the necessity of timely colostrum intake and investigated diagnostic and stall-side assays such as the zinc sulfate turbidity, total protein, and radial immunodiffusion to quantify serum IgG levels in neonatal foals. Studies have expanded to examine the influence of maternal health and nutrition during pregnancy and the impact those factors have on colostrum quality, including IgG concentration. In modern times, IgG continues to be a cornerstone of diagnostic and therapeutic strategies, and advances in molecular immunology and monoclonal antibody technology have enabled detailed characterization of IgG subclasses. This has enhanced our understanding of their roles in vaccine response, allergic disease, and chronic infections. A recent key advancement in our understanding of IgG dynamics has been the elucidation of the role of the neonatal Fc receptor (FcRn) in several livestock species. FcRn is responsible for protecting IgG from lysosomal degradation, thereby extending its half-life and maintaining serum IgG levels. This receptor not only underlies the success of passive transfer but also has implications for the design of IgG-based therapeutics. Although our understanding of IgG in horses has significantly advanced over the years, challenges remain, including variability in IgG response due to genetic and environmental factors, limited equine subclass-specific reagents, and the ongoing need to support fundamental functional research to deepen our understanding of IgG biology. Nonetheless, the evolution of IgG research in horses reflects broader trends in veterinary immunology and highlights the antibody’s enduring importance across developmental, diagnostic, and therapeutic categories. Continued multidisciplinary efforts will be crucial to advancing the molecular understanding of IgG mechanisms and leveraging its biological capabilities to optimize equine health.

Role of immunoglobulin M in Trachinotus ovatus defense against Cryptocaryon irritans infection.

Psychological Stress-Induced Local Immune Response to Food Antigens Increases Pain Signaling Across the Gut in Mice.

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an immune-mediated disease of the peripheral nerves characterized by proximal and distal muscle weakness and sensory abnormalities. CIDP has been associated with various pathophysiological mechanisms that are not fully understood and that likely differ across groups of patients. It has been proposed that an interplay of different immunopathological mechanisms including the cellular, humoral and complement pathways play a key role in peripheral nerve damage in CIDP. Currently approved treatments and therapies in research often target different potential pathophysiological mechanisms. The efficacy of these different treatments can shed light on the prominence of particular pathophysiological pathways in subsets of patients with CIDP. For example, the complement pathway plays a key role in promoting macrophage-mediated demyelination, and complement inhibitors are under development as new targets in CIDP treatment, with mixed results. The neonatal Fc receptor (FcRn) has also been targeted as a promising treatment avenue due to its role in immunoglobulin G degradation. Efgartigimod is the first FcRn blocker approved for the treatment of CIDP. This review provides an overview of key proposed mechanisms of action in CIDP pathophysiology in the context of both basic scientific findings and treatment targets in recent clinical studies.

Evidence on the role of immunoglobulin E (IgE) sensitization in acute food protein-induced enterocolitis syndrome (atypical FPIES) is limited. Initial reports claimed association with persistent disease; however, recent studies have not replicated this. To systematically review the relationship between sensitization to the culprit food(s) in acute FPIES and the outcome of follow-up oral food challenges. To assess the rates of sensitization, seroconversion (ie, switch from negative tests to sensitization), and phenotype switch to IgE-mediated food allergy over time in individuals with acute FPIES. Systematic review searching 10 databases. Studies of children and adults with an acute FPIES diagnosis assessing IgE sensitization to a culprit food at onset or follow-up measured by skin prick or serological test were included. Of 1,830 studies identified, 53 were eligible including 3,514 participants. Ten studies had an analytical design assessing whether sensitization was associated with disease persistence, with 4 showing an association and 6 showing no association. In individuals with acute FPIES, the sensitization rate was 9.8% (95% confidence interval [95% CI 7.4%-12.1%; 34 studies, 2,587 participants, I2= 82%); the frequency of seroconversion was 1.1% (95% CI 0.1%-2.1%; 9 studies, 673 participants, I2= 32%); and phenotype switch occurred in 1.1% (95% CI 0.4%-1.7%; 14 studies, 935 participants, I2= 0%) and 13% (95% CI 5.5%-20.5%, 12 studies, 93 participants; I2= 18%) of sensitized participants. We did not find consistent evidence for the relationship between IgE sensitization and FPIES persistence. We found phenotype switch to IgE-mediated food allergy is uncommon in acute FPIES. An IgE sensitization in FPIES does not have a clear relationship with clinical outcomes.

Sepsis is a life-threatening syndrome caused by an imbalance in the inflammatory response to an infection that can lead to a high mortality rate. Escherichia coli is a common pathogen that causes sepsis. The role of immunoglobulin G N-glycome in estimating the mortality in patients with sepsis remains unknown. This study aims to reveal the clinical application of immunoglobulin G N-glycome as a potentially novel biomarker to predict mortality risk in Escherichia coli-induced sepsis. The serum immunoglobulin G N-glycome levels in 100 adult septic patient serum samples on the day of intensive care unit (ICU) admission, and 100 healthy volunteers were measured and analyzed. Immunoglobulin G N-glycome was compared with existing risk scores on predicting in-hospital death. We identified that the fucosylation level was significantly decreased in patients. Importantly, bisecting GlcNAc, sialylation, and galactosylation have different levels between sepsis and control groups. In addition, the AUC values of the SOFA score combined with GP4, GP5, and GP9 were 0.76 (95%CI: 0.61 to 0.90), 0.58 (95%CI: 0.40 to 0.7) and 0.57 (95%CI: 0.38 to 0.76). The AUC value of the SOFA score combined with GP4 and GP7 was 0.85 (95%CI: 0.76 to 0.93) in predicting in-hospital mortality in patients with sepsis. Immunoglobulin G N-glycome concentrations at ICU admission are valuable for predicting the in-hospital mortality risk of patients with sepsis, suggesting that immunoglobulin G N-glycome may be a novel biomarker.

The role of immunoglobulin G (IgG) responses to food as potential triggering factors in allergic disorders continues to be debatable, and is not endorsed by most allergy societies. To explore the prevalence of specific IgG immune responses to common foods in pediatric allergic disorders and any potential relationship between them. A retrospective study was conducted on children and adolescents diagnosed with allergic disorders at the Ekthar Clinic in Jeddah City. Food-specific IgG (FS-IgG) antibody test results were collected from their medical records. Seventy-five children with a mean age of 8.5 years (SD = 5.3) were included. The overall allergic diagnosis determined atopic dermatitis as the most common (57.3%, 43 participants), followed by food allergy and allergic rhinitis (each 40%, 30 participants), and bronchial asthma (29.3%, 22 participants). Food-specific IgG levels were elevated in all participants. The foods with the highest levels of FS-IgG were dairy products (88%: cow's milk [86.6%], sour milk [81.3%], sheep's milk [74.7%], cheese [72%], and goat's milk [70.7%]), followed by gluten-containing products (81.3%: wheat [70.7%], gluten [69.3%], and spelt [66.6%]), and eggs (66.6%). Significant correlations (P < 0.05) were found between atopic dermatitis and several foods; chronic urticaria and chicken and lamb; asthma and ocean perch; allergic rhinitis and rennet cheese; and allergic conjunctivitis and potato, pollock, and lamb. Among pediatric allergic disorders, dairy, gluten, and eggs were the most detected foods in FS-IgG tests, with some notable correlations with other foods. FS-IgG testing may help identify potential triggers in refractory allergic disorders.

The endothelin system is reported to play a significant role in glomerular and tubulointerstitial kidney disease. In the kidney, endothelins are produced in mesangial cells and the glomerular basement membrane by the endothelium and podocytes. The endothelin system regulates glomerular function by inducing proliferation, increasing permeability and in effect proteinuria, and stimulating inflammation, tubular fibrosis, and glomerular scarring. Endothelin A receptor antagonists have been proven to delay the progression of chronic kidney disease and play a protective role in immunoglobulin A nephropathy, focal segmental glomerulosclerosis, and diabetic nephropathy. There are several ongoing research studies with ETAR antagonists in nondiabetic nephropathy, Alport disease, vasculitis and scleroderma nephropathy, which results are promising. Some reports suggest that the endothelin system might contribute to ischemia-reperfusion injury, acute graft rejection and deterioration of graft function. Endothelin inhibition in renal transplantation and its influence on graft survival is the future direction needing further research. The most frequent side effects associated with ETAR antagonists is fluid retention. Additionally, it should be considered if selective ETAR antagonists therapy needs to be co-administered with sodium-glucose co-transporter 2 inhibitors, renin-angiotensin-aldosterone inhibitors or diuretics and which patients should be recruited to such treatment to minimize the risk of adverse outcomes.

Neutrophils are emerging as promising candidates for cell-based nanodrug delivery to tumors due to their unique biological properties. This study aims to investigate the mechanisms of nanoparticle internalization by neutrophils, specifically focusing on liposomes, poly(lactic-co-glycolic acid) (PLGA), and magnetite nanoparticles. Understanding these mechanisms could enhance the efficiency of neutrophil-based nanodrug delivery for cancer treatment. Neutrophils were isolated from the peripheral blood of mice bearing 4T1 mammary adenocarcinoma. Confocal microscopy, transmission electron microscopy, and flow cytometry were employed to evaluate the uptake of liposomes, PLGA, and magnetite nanoparticles by neutrophils. The effects of cultivation conditions, such as the presence or absence of plasma in the growth medium, were also examined. Additionally, the roles of immunoglobulins (IgG/IgM) and cell surface receptors (Fc and scavenger receptors) in nanoparticle internalization were explored. All types of nanoparticles were successfully internalized by neutrophils, though the mechanisms of uptake varied. Plasma presence in the medium significantly influenced nanoparticle binding, particularly for PLGA nanoparticles. Internalization of PLGA nanoparticles was found to depend on the presence of IgG/IgM in the medium and Fc receptors on neutrophil surfaces, while scavenger receptors were not involved. Understanding the distinct endocytosis pathways for different nanoparticles can improve the efficacy of neutrophil loading with nanodrugs, potentially advancing the development of neutrophil-based cancer therapies. The findings underscore the importance of the extracellular environment in modulating nanoparticle uptake.

BackgroundA case-control study was conducted to analyze the role of cerebrospinal fluid immunoglobulin in the differential diagnosis of autoimmune encephalitis and viral encephalitis in children.MethodsOne hundred and twenty patients with autoimmune encephalitis (AE) treated in our hospital from February 2021 to February 2022 were included as the observation group (AE group). 100 patients with viral encephalitis (VE group) were selected as the control group. The clinical data of all patients were collected and analyzed retrospectively. Immunoglobulin G (IgG) and immunoglobulin A (IgA)in cerebrospinal fluid of the two patients were measured by immune turbidimetry. Immunoglobulin M (IgM), and the diagnostic value of immunoglobulin in cerebrospinal fluid (CSF) in patients with AE was analyzed by receiver working curve (ROC).ResultsThe level of IgG in the cerebrospinal fluid of the AE group was higher than that of the VE group, and the level of IgM was lower than that of the VE group, and the difference was statistically significant (P < 0.05). There was no significant difference in IgA levels between the two groups (P > 0.05). In terms of Magnetic Resonance (MR) features, the paraventricular, hippocampal, occipital and parietal lobes were more involved in AE patients, frontal and temporal lobes were more involved in VE patients, and paraventricular and occipital lobes were involved in MS. The proportion of bilateral extensive lesions in both groups was significantly higher than 50%. The proportions of patients in the AE group involving the lateral ventricle, insula, and parietal lobes were significantly higher than those in the VE group, and the proportions involving the basal ganglia, temporal lobes, and frontal lobes were significantly lower than those in the VE group, and the differences were statistically significant (All P < 0.05). The Area Under Curve (AUC) of IgG, IgA and IgM alone in the diagnosis of AE were 0.795(0.587–0.762), 0.602(0.502–0.631) and 0.627(0.534–0.708), respectively with the sensitivity values of 81.24% and 65.608, respectively and the specificity values of 65.08%, 57.54% and 75.01% respectively. The AUC of IgA + IgM in the diagnosis of AE was 0.733(0.617–0.849), and the sensitivity and specificity are 62.58% and 75.07% respectively. The AUC of IgA + IgG in the diagnosis of AE was 0.823(0.730–0.917), and the sensitivity and specificity were 81.24% and 67.54% respectively. The AUC of IgG + IgM in the diagnosis of AE was 0.886(0.814 ~ 0.958), and the sensitivity and specificity were 84.48% and 77.59% respectively. The AUC of IgA + IgM + IgG in the diagnosis of AE was 0.924 (0.868–0.981) with the sensitivity of 93.82%, and the specificity of 77.56%.ConclusionThe level of immunoglobulin in cerebrospinal fluid can be used as an effective reference index for the diagnosis of AE. The combined detection of IgA, IgM and IgG can improve the accuracy, sensitivity and specificity of AE.

BackgroundRecent studies have found that total immunoglobulin E (IgE) and allergen-specific IgE were associated with some metabolic diseases. However, the role of IgE in metabolism among adolescents is still unclear. Herein, this study aims to investigate the associations of serum total IgE and allergen-specific IgE with insulin resistance (IR) in adolescents, in order to provide some reference for the prevention and treatment of metabolic diseases in a young age.MethodsData of 870 adolescents were extracted from the National Health and Nutrition Examination Survey (NHANES) database in 2005–2006 in this cross-sectional study. Weighted univariate and multivariate logistic regression analyses were utilized to screen covariates and explore the relationships of serum total IgE and allergen-specific IgE with IR. The evaluation indexes were odds ratios (ORs) and 95% confidence intervals (CIs). In addition, these relationships were also assessed in subgroups of allergy history, asthma history, and number of allergens.ResultsAmong eligible adolescents, 168 had IR. No significant association between serum total IgE level and IR was found. However, adolescents with higher level of allergen-specific IgE to rye grass [OR = 0.47, 95%CI: (0.25–0.91)], white oak [OR = 0.57, 95%CI: (0.37–0.88)], or peanut [OR = 0.38, 95%CI: (0.15–0.97)] seemed to have lower odds of IR, whereas those had higher level of shrimp-specific IgE [OR = 2.65, 95%CI: (1.21–5.84)] have increased odds of IR. In addition, these associations between allergen-specific IgE and IR were also discovered in adolescents who had allergy history or asthma history, or had different numbers of allergens.ConclusionPaying attention to different allergens in adolescents may be important in the early identification of IR among this high-risk population. The study results relatively provided some reference for further exploration on IR prevention.

Artificial intelligence-driven design of the assembled major cat allergen Fel d 1 to improve its spatial folding and IgE-reactivity

Here we report a case of congenital CMV infection with rare presentation as haemolytic anaemia in a 50-day-old infant. Clinical manifestations of our patient were pallor, jaundice, hepatosplenomegaly, and a deranged coagulation profile. Congenital CMV being the most common viral congenital infection should be suspected in every neonate and infant presenting with haemolytic anaemia. It is also the most common non-genetic cause of SNHL and not much is yet there for its prevention except for primary prevention as the role of immunoglobulin is still under trial.

MZB1-mediated IgA secretion suppresses the development and progression of colorectal cancer triggered by gut inflammation

Necesidades no cubiertas en asma alérgica grave

Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) are a clinical syndrome characterized by the abrupt onset of major personality, movement, and behavioral changes in a patient with a history of streptococcal infection. We aimed to do a bibliometric analysis of the published research on PANDAS. All the published articles available on the PubMed database from the time of inception till August 2022 were included in the study. All the PubMed IDs (PMID) of the articles were entered in Harvard Catalyst, a free online software, for bibliometric analysis, and data were extracted and verified. A total of 289 relevant published articles were identified. The average number of authors per article was 4.89 and the average number of times an article was cited was 11.19 (excluding self-citation). The H-index of the published articles was 31. The Journal of Child and Adolescent Psychopharmacology published the maximum number of articles ( n = 36). The highest number of average citations (39.50 citations/articles) was for the articles published in the American Journal of Psychiatry. The most common type of articles were journal articles ( n = 259) and of which 27 were original research articles. Most of the original research discusses the effectiveness of various interventions (penicillin and other antibiotic prophylaxis, role of immunoglobulin), neuropsychiatric symptoms, and outcomes in the longitudinal course. Though PANDAS is a well-researched entity, more clinical trials, and large-scale studies will help provide better insight on this subject.

Sibeprenlimab blocks the cytokine "A Proliferation-Inducing Ligand" (APRIL), which may play a key role in immunoglobulin A nephropathy pathogenesis. A phase 1 study of subcutaneous (SC) sibeprenlimab evaluated preliminary safety, tolerability, pharmacokinetics, and pharmacodynamics in healthy participants. This was an open-label, single-ascending-dose study. Twelve participants in each of 4 sequential dosing cohorts received 1 SC dose of sibeprenlimab (200mg [1×1mL injection], 400mg [2×1mL injections], 400mg [1×2mL injection], or 600mg [1 mL+2mL injections]) and underwent 16-week follow-up for adverse events, pharmacokinetics, and pharmacodynamics (serum APRIL, immunoglobulin [Ig] levels). Sibeprenlimab in single SC doses of 200-600mg was slowly absorbed into the systemic circulation, with a median time to maximum serum concentration of approximately 6-10.5 days, and a mean elimination half-life of approximately 8-10 days. Serum APRIL, IgA, IgM, and, to a lesser extent, IgG decreased in a dose-dependent and reversible manner. Maximal reduction in serum IgA was approximately 60% at the 400- and 600-mg doses and 40% at 200mg. Serum APRIL rapidly decreased to near the lower limit of quantification, and duration of suppression was dose-dependent, with near complete suppression until weeks 4-6 at the 400-mg dose and week 8 at the 600-mg dose. Adverse events occurred in 30/48 (62.5%) participants; none were serious or led to study discontinuation. Sibeprenlimab rapidly and sustainably reduced target APRIL and Ig biomarkers in a dose-dependent and reversible manner, with acceptable preliminary safety and pharmacokinetics.