Serum IgG Research Articles

Longitudinal changes in serum immunoglobulin G testing in patients with fibrotic avian hypersensitivity pneumonitis

BackgroundEvaluation of the antigen responsible for fibrotic hypersensitivity pneumonitis (HP) is challenging. Serum immunoglobulin (Ig) G testing against HP-associated antigens is performed. Although single-serum IgG testing has been investigated, multiple-serum IgG testing has not yet been studied.MethodsThis study included patients who underwent histopathological examination and positive inhalation challenge test as well as those with moderate or high HP guideline confidence level. Serum IgG testing against pigeon serum was conducted twice using two methods: enzyme linked-immunosorbent assay (ELISA) and ImmunoCAP. The association between changes in serum IgG antibody titers and changes in forced vital capacity (FVC) and other parameters was investigated.ResultsIn this study, 28 patients (mean age, 64.5 years; mean FVC, 85.3%) with fibrotic avian HP were selected, of whom 20 and 8 underwent surgical lung biopsy and transbronchial lung cryobiopsy, respectively. Of the 28 patients, 19 had been keeping birds for more than 6 months. A correlation was observed between the annual changes in serum IgG antibody titers by ELISA and changes in relative FVC (r = − 0.6221, p < 0.001). Furthermore, there was a correlation between the annual changes in serum IgG antibody titers by ImmunoCAP and changes in relative FVC (r = − 0.4302, p = 0.022). Multiple regression analysis revealed that the change in serum IgG antibody titers by both ELISA and ImmunoCAP also influenced the relative FVC change (p = 0.012 and p = 0.015, respectively). Moreover, 13 patients were given additional treatments between the first and second blood test; however, the additional treatment group was not significantly different in relative FVC change compared to the group with no additional treatment (p = 0.982).ConclusionsIn patients with fibrotic avian HP, the annual changes in serum IgG testing were correlated with FVC changes, highlighting the importance of serum IgG testing over time.

The Effect of Age and Comorbidities: Children vs. Adults in Their Response to SARS-CoV-2 Infection

While children have experienced less severe coronavirus disease (COVID-19) after SARS-CoV-2 infection than adults, the cause of this remains unclear. The objective of this study was to describe the humoral immune response to COVID-19 in child vs. adult household contacts, and to identify predictors of the response over time. In this prospective cohort study, children with a positive SARS-CoV-2 polymerase chain reaction (PCR) test (index case) were recruited along with their adult household contacts. Serum IgG antibodies against SARS-CoV-2 S1/S2 spike proteins were compared between children and adults at 6 and 12 months after infection. A total of 91 participants (37 adults and 54 children) from 36 families were enrolled. Overall, 78 (85.7%) participants were seropositive for anti-S1/S2 IgG antibody at 6 months following infection; this was higher in children than in adults (92.6% vs. 75.7%) (p = 0.05). Significant predictors of a lack of SARS-CoV-2 seropositivity were age ≥ 25 vs. &lt; 12 years (odds ratio [OR] = 0.23, p = 0.04), presence of comorbidities (vs. none, adjusted OR = 0.23, p = 0.03), and immunosuppression (vs. immunocompetent, adjusted OR = 0.17, p = 0.02).

Robot-assisted thoracoscopic resection of a posterior mediastinal tumor with immunoglobulin G4-related disease: a case report

BackgroundImmunoglobulin (Ig)G4-related disease affects nearly every organ, and its clinical course varies depending on the involved organ; however, its occurrence in the mediastinum is rarely reported.Case presentationA 58-year-old woman presented with a posterior mediastinal tumor along the thoracic spine on imaging. Based on her elevated serum IgG4 level of 349.7 mg/dL, IgG4-related disease was suspected. Since the tumor was growing and malignancy could not be excluded, surgical resection was performed for definitive diagnosis. Robot-assisted thoracoscopic surgery was performed via the left semipronation and right thoracic approaches. The irregularly-shaped tumor was located on the level of the seventh to ninth thoracic vertebra, along the sympathetic nerve. A malignancy was not excluded based on the appearance of the tumor. The tumor had poor mobility. The sympathetic nerves, intercostal arteries, and veins were also excised. In this case, the articulated forceps, used during the robotic surgery, were useful in achieving complete tumor resection along the vertebral body. The pathological examination revealed IgG4-positive plasma infiltration, which fulfilled the criteria for IgG4-related diseases. The postoperative course was uneventful, and the patient underwent follow-up on an outpatient basis without additional medications.ConclusionThe clinical presentation of IgG4-related disease varies, based on the involved organs. This case was rare because the mediastinum was involved, and it emphasized the effectiveness of surgical resection.

HLA dependency and possible clinical relevance of intrathecally synthesized anti-IgLON5 IgG4 in anti-IgLON5 disease.

Anti-IgLON5 disease is a rare chronic autoimmune disorder characterized by IgLON5 autoantibodies predominantly of the IgG4 subclass. Distinct pathogenic effects were described for anti-IgLON5 IgG1 and IgG4, however, with uncertain clinical relevance. IgLON5-specific IgG1-4 levels were measured in 46 sera and 20 cerebrospinal fluid (CSF) samples from 13 HLA-subtyped anti-IgLON5 disease patients (six females, seven males) using flow cytometry. Intervals between two consecutive serum or CSF samplings (31 and 10 intervals, respectively) were categorized with regard to the immunomodulatory treatment active at the end of the interval, changes of anti-IgLON5 IgG1 and IgG4 levels, and disease severity.Intrathecal anti-IgLON5 IgG4 synthesis (IS) was assessed using a quantitative method. The median age at onset was 66 years (range: 54-75), disease duration 10 years (range: 15-156 months), and follow-up 25 months (range: 0-83). IgLON5-specific IgG4 predominance was observed in 38 of 46 (83%) serum and 11 of 20 (55%) CSF samples. Anti-IgLON5 IgG4 levels prior clinical improvement in CSF but not serum were significantly lower than in those prior stable/progressive disease. Compared to IgLON5 IgG4 levels in serum, CSF levels in HLA-DRB1*10:01 carriers were significantly higher than in non-carriers. Indeed, IgLON5-specific IgG4 IS was demonstrated not only in four of five HLA-DRB1*10:01 carriers but also in one non-carrier. Immunotherapy was associated with decreased anti-IgGLON5 IgG serum levels. In CSF, lower anti-IgLON5 IgG was associated with immunosuppressive treatments used in combination, that is, corticosteroids and/or azathioprine plus intravenous immunoglobulins or rituximab. Our findings might indicate that CSF IgLON5-specific IgG4 isfrequently produced intrathecally, especially in HLA-DRB1*10:01 carriers.Intrathecally produced IgG4 may be clinically relevant. While manyimmunotherapies reduce serum IgLON5 IgG levels, more intense immunotherapies induce clinical improvement and may be able to target intrathecally produced anti-IgLON5 IgG. Further studies need to confirm whether anti-IgLON5 IgG4 IS is a suitable prognostic and predictive biomarker in anti-IgLON5 disease.

Autoimmune Hepatitis Management: Recent Advances and Future Prospects

Autoimmune hepatitis (AIH) is a varied inflammatory chronic liver disease. AIH’s prevalence varies and has increased recently. Diagnosis involves the discovery of histologic features following liver biopsy and serologic testing. Clinical features vary, and up to 40% of patients may be asymptomatic. Evaluating thiopurine methyltransferase (TMPM) activity before treatment is crucial for an optimal response. The primary treatment goal is biochemical remission, normalized serum IgG, and liver enzymes. Induction therapy typically involves azathioprine and corticosteroids. Close monitoring of liver function tests and serum immunoglobulin levels is essential. Medications can be tapered after achieving biochemical remission. Liver transplantation may be required for refractory disease or cirrhosis. Further therapeutic approaches are needed, particularly for non-responders to first-line treatments.

Optimized Enzyme-Linked Immunosorbent Assay for Anti-PEG Antibody Detection in Healthy Donors and Patients Treated with PEGylated Liposomal Doxorubicin.

There is considerable interest in quantifying anti-PEG antibodies, given their potential involvement in accelerated clearance, complement activation, neutralization, and acute reactions associated with drug delivery systems. Published and commercially available anti-PEG enzyme-linked immunosorbent assays (ELISAs) differ significantly in terms of reagents and conditions, which could be confusing to users who want to perform in-house measurements. Here, we optimize the ELISA protocol for specific detection of anti-PEG IgG and IgM in sera from healthy donors and in plasma from cancer patients administered with PEGylated liposomal doxorubicin. The criterion of specificity is the ability of free PEG or PEGylated liposomes to inhibit the ELISA signals. We found that coating high-binding plates with monoamine methoxy-PEG5000, as opposed to bovine serum albumin-PEG20000, and blocking with 1% milk, as opposed to albumin or lysozyme, significantly improve the specificity, with over 95% of the signal being blocked by competition. Despite inherent between-assay variability, setting the cutoff value of the optical density at the 80th percentile consistently identified the same subjects. Using the optimized assay, we longitudinally measured levels of anti-PEG IgG/IgM in cancer patients before and after the PEGylated liposomal doxorubicin chemotherapy cycle (1 month apart, three cycles total). Antibody titers did not show any increase but rather a decrease between treatment cycles, and up to 90% of antibodies was bound to the infused drug. This report is a step toward harmonizing anti-PEG assays in human subjects, emphasizing the cost-effectiveness and optimized specificity.

The efficacy of cercarial antigen loaded on nanoparticles as a potential vaccine candidate in Schistosoma mansoni-infected mice.

Schistosomiasis is one of the most common causes of morbidity and mortality from parasitic diseases. Mass treatment has proven to be insufficient because of repeated infection after treatment and the appearance of strains resistant to drug therapy. Hence, immunization is a new approach to control the disease and limit the pathological consequences of schistosomiasis. To evaluate the prophylactic effect of Cercarial antigen (CAP) loaded on chitosan nanoparticles (CSNPs) as a potential vaccine against Schistosoma mansoni-infected mice. 130 mice divided into 2 groups were used: Group I: Control groups (50 mice) subdivided into subgroup Ia (10 mice): Non-infected mice (normal control), subgroup Ib (20 mice): Schistosoma infected mice (infected control) and subgroup Ic (20 mice): Non-infected mice receiving NPs only. Group II: Vaccinated group (80 mice) subdivided equally into subgroup IIa (CAP): Received cercarial antigen and subgroup IIb (CAP + CSNP): Received cercarial antigen loaded on chitosan NPs then both vaccinated groups were infected with S. mansoni 3 weeks following the initial vaccination dose. CAP + CSNP and CAP groups showed significant reduction in adult worms count, hepatic egg count, hepatic granulomas number and size in comparison to the infected control group. Elevation of serum IgG and IgM levels, CD4+ and CD8+ T cell frequencies, IL-4, IL-10 and INF-γ levels was more significant in CAP + CSNP group than CAP group. CAP + CSNP is a promising new preparation of Schistosomal antigens that gave better results than immunization with CAP alone. CSNPs enhanced the immune and protective effect of CAP as validated by parasitological, histopathological and immunohistochemical studies.

Intranasal respiratory syncytial virus vaccine attenuated by codon-pair deoptimization of seven open reading frames is genetically stable and elicits mucosal and systemic immunity and protection against challenge virus replication in hamsters.

Respiratory syncytial virus (RSV) is the most important viral agent of severe pediatric respiratory illness worldwide, but there is no approved pediatric vaccine. Here, we describe the development of the live-attenuated RSV vaccine candidate Min AL as well as engineered derivatives. Min AL was attenuated by codon-pair deoptimization (CPD) of seven of the 11 RSV open reading frames (ORFs) (NS1, NS2, N, P, M, SH and L; 2,073 silent nucleotide substitutions in total). Min AL replicated efficiently in vitro at the permissive temperature of 32°C but was highly temperature sensitive (shut-off temperature of 36°C). When serially passaged at increasing temperatures, Min AL retained greater temperature sensitivity compared to previous candidates with fewer CPD ORFs. However, whole-genome deep-sequencing of passaged Min AL revealed mutations throughout its genome, most commonly missense mutations in the polymerase cofactor P and anti-termination transcription factor M2-1 (the latter was not CPD). Reintroduction of selected mutations into Min AL partially rescued its replication in vitro at temperatures up to 40°C, confirming their compensatory effect. These mutations restored the accumulation of positive-sense RNAs to wild-type (wt) RSV levels, suggesting increased activity by the viral transcriptase, whereas viral protein expression, RNA replication, and virus production were only partly rescued. In hamsters, Min AL and derivatives remained highly restricted in replication in the upper and lower airways, but induced serum IgG and IgA responses to the prefusion form of F (pre F) that were comparable to those induced by wt RSV, as well as robust mucosal and systemic IgG and IgA responses against RSV G. Min AL and derivatives were fully protective against challenge virus replication. The derivatives had increased genetic stability compared to Min AL. Thus, Min AL and derivatives with selected mutations are stable, attenuated, yet highly-immunogenic RSV vaccine candidates that are available for further evaluation.

Associations between periodontitis and serum anti-malondialdehyde-acetaldehyde antibody concentrations in rheumatoid arthritis: A case-control study.

Malondialdehyde-acetaldehyde (MAA) adducts lead to generation of anti-MAA autoantibodies and have been independently identified in inflamed periodontal and rheumatoid arthritis (RA) tissues. This study evaluates serum samples from RA cases and osteoarthritis (OA) controls to quantify associations between periodontal clinical measures, alveolar bone loss (ABL), and anti-Porphyromonas gingivalis, anti-Prevotella intermedia, and anti-Fusobacterium nucleatum antibody concentrations with anti-MAA antibody concentrations. Participants (n=284 RA cases, n=330 OA controls) underwent periodontal clinical assessments and ABL measurements. Serum immunoglobulin (Ig) A, IgG, and IgM anti-MAA and serum IgG antibacterial antibody concentrations were quantified by enzyme-linked immunosorbent assay (ELISA). Analyses utilized simple linear regression and multivariable adjusted models. No significant associations of periodontal clinical measures with serum anti-MAA were found. Moderate (p=0.038 and p=0.036, respectively) and high ABL (p=0.012 and p=0.014, respectively) in RA cases (but not in OA) were positively associated with IgG and IgM anti-MAA. Anti-P. gingivalis and anti-P. intermedia antibody concentrations were positively associated with IgA (p=0.001 for both), IgG (p=0.007 and p=0.034, respectively), and IgM anti-MAA antibody concentrations (p<0.001 and p=0.020, respectively), while anti-F. nucleatum was positively associated with IgG anti-MAA (p=0.042), findings that were similar across groups. A positive association was demonstrated between ABL and serum IgG and IgM anti-MAA antibody concentrations that was unique to RA and not observed in OA. Serum anti-P. gingivalis, anti-P. intermedia, and anti-F. nucleatum antibody concentrations displayed significant associations with anti-MAA antibody in both groups. These findings suggest MAA may play a role in the interrelationship between the periodontium and RA.

Bayesian estimation of sensitivity and specificity of IgG and serum total protein cutoff values for the diagnosis of failed transfer of passive immunity in neonatal beef calves

Calves with failed transfer of passive immunity (FTPI) possess increased risk of preweaning disease. Common tests for FTPI such as radial immunodiffusion (RID) and optical refractom­etry (OR) have inherent imprecision. The objective of this study was to estimate test sensitivity and specificity for various IgG concentrations and serum total protein values (STP) to classify neonatal beef calves with FTPI.

Questionable Immunity to Mumps among Healthcare Workers in Italy-A Cross-Sectional Serological Study.

Highly contagious diseases, such as mumps, are a global concern as new epidemics continue to emerge, even in highly vaccinated populations. The risk of transmission and spread of these viruses is even higher for individuals who are more likely to be exposed, including healthcare workers (HCWs). In healthcare settings, both HCWs and patients are at risk of infection during the care process, potentially leading to nosocomial epidemic outbreaks. Mumps is often underestimated compared with measles and rubella, despite being milder and less likely to spread. In fact, the risk of complications following mumps infection is extremely high, especially if the disease occurs in adulthood. The measles-mumps-rubella (MMR) vaccine has been shown to be an excellent preventive measure. Unfortunately, the mumps component appears to be less effective in inducing immunity than those for measles and rubella (two-dose effectiveness of 85%, 95% and 97%, respectively). The main aim of our study was to investigate the prevalence of detectable mumps antibodies (serum IgG antibodies) in a cohort of Italian and foreign HCWs in relation to personal and occupational factors. We included in the study 468 subjects who underwent health surveillance at the Occupational Medicine Unit of the Tor Vergata Polyclinic in Rome during the period from January 2021 to March 2023. In our study, the proportion of HCWs found to be unprotected against mumps was very high (8.3%), and those found to be immune are below the WHO threshold for herd immunity (95%). From our data, it seems essential that all occupational health services carry out an accurate screening with a dose of anti-mumps antibodies to assess serological protection before starting a job, regardless of an individual's vaccination history. This approach is proving to be beneficial, accurate, as it allows all serologically non-immune individuals to be vaccinated in the workplace, including those who would be protected by their vaccination history but have lost the antibody response.

Circulating Autoantibody Profiling Identifies LIMS1 as a Potential Target for Pathogenic Autoimmunity in pathologic Myopia

High myopia is a leading cause of blindness worldwide, among which pathologic myopia, characterized by typical myopic macular degeneration, is the most detrimental. However, its pathogenesis remains largely unknown. Here, using a HuProt array, we first initiated a serological autoantibody profiling of high myopia and identified 18 potential autoantibodies, of which anti-LIMS1 autoantibody was validated by a customized focused microarray. Further subgroup analysis revealed its actual relevance to pathologic myopia, rather than simple high myopia without myopic macular degeneration. Mechanistically, anti-LIMS1 autoantibody predominantly belonged to IgG1/IgG2/IgG3 subclasses. Serum IgG obtained from patients with pathologic myopia could disrupt the barrier function of retinal pigment epithelial cells via cytoskeleton disorganization and tight junction component reduction, and also trigger a pro-inflammatory mediator cascade in retinal pigment epithelial cells, which were all attenuated by depletion of anti-LIMS1 autoantibody. Together, these data uncover a previously unrecognized autoimmune etiology of myopic macular degeneration in pathologic myopia.

Improving broiler health through cecal microbiota transplantation: a comprehensive study on growth, immunity, and microbial diversity.

Cecal microbiota has emerged as a prominent intervention target for improving the production and welfare of poultry. This is essential for the overall health and performance of broiler chickens. The current study focused on investigating the effect of cecal microbiota transplantation (CMT) from healthy donor chickens on the growth performance, immunity, and microbial composition of newly hatched chicks and evaluated the effect of sample storage on the microbial diversity of the cecal samples. A healthy "Wannan Yellow Chicken line" was selected as the donor, and 180 1-d-old chicks from the same line were used as recipients for a 60-d feed trial. The chicks were randomly allocated to three groups (60 birds per group) with three replicates in each group. The three treatment groups were CMT-0 (control, normal saline solution), CMT-I (1:12 cecal content, normal saline supplemented with 10% glycerol), and CMT-II (1:6 cecal content, normal saline supplemented with 10% glycerol). The results of weight gain and absolute organ weight showed significant improvements in the CMT-II group compared with the CMT-0 group. Serum IgG level was significantly improved (P < 0.05) in CMT-I compared with that in the CMT-0. However, IL-6 levels increased in CMT-I and then significantly decreased in CMT-II. The cecal microbial diversity of CMT treatment was compared between two groups, fresh samples (FS) and stored samples at-80 °C (SS). The results showed that beneficial taxa, such as Firmicutes and Verrucomicrobiota, were substantially more abundant in both CMT-I and CMT-II than in CMT-0 in both FS and SS. Microbial function analysis at levels 1, 2, and 3 showed improved metabolism, genetic information processing, cellular processes, environmental information processing, and organismal systems in CMT-I and CMT-II for both FS and SS groups. However, the SS group showed decreased microbial diversity and function. To conclude, cecal microbiota transplantation is a promising strategy for enhancing the productivity and health of broiler chickens.

Gut Microbiome-Serum Metabolism Revealed the Allergenicity of Ferulic Acid Combined with Glucose-Modified β-Lactoglobulin.

A novel strategy combining ferulic acid and glucose was proposed to reduce β-lactoglobulin (BLG) allergenicity and investigate whether the reduction in allergenicity was associated with gut microbiome and serum metabolism. As a result, the multistructure of BLG changed, and the modified BLG decreased significantly the contents of IgE, IgG, IgG1, and mMCP-1 in serum, improved the diversity and structural composition of gut microbiota, and increased the content of short-chain fatty acids (SCFAs) in allergic mice. Meanwhile, allergic mice induced by BLG affected arachidonic acid, tryptophan, and other metabolic pathways in serum, the modified BLG inhibited the production of metabolites in arachidonic acid metabolism pathway and significantly increased tryptophan metabolites, and this contribution helps in reducing BLG allergenicity. Overall, reduced allergenicity of BLG after ferulic acid was combined with glucose modification by regulating gut microbiota, the metabolic pathways of arachidonic acid and tryptophan. The results may offer new thoughts alleviating the allergy risk of allergenic proteins.

Magnetic resonance imaging characteristics of Graves orbitopathy with elevated IgG4 serum concentration

Magnetic resonance imaging characteristics of Graves orbitopathy with elevated IgG4 serum concentration

A pediatric randomized, controlled trial of German cockroach subcutaneous immunotherapy

Cockroach allergy contributes to morbidity among urban children with asthma. Few trials address the effect of subcutaneous immunotherapy (SCIT) with cockroach allergen among these at-risk children. We sought to determine whether nasal allergen challenge (NAC) responses to cockroach allergen would improve following 1 year of SCIT. Urban children with asthma, who were cockroach-sensitized and reactive on NAC, participated in a year-long randomized double-blind placebo-controlled SCIT trial using German cockroach extract. The primary endpoint was the change in mean Total Nasal Symptom Score (TNSS) during NAC after 12 months of SCIT. Changes in nasal transcriptomic responses during NAC, skin prick test wheal size, serum allergen-specific antibody production, and T-cell responses to cockroach allergen were assessed. Changes in mean NAC TNSS did not differ between SCIT-assigned (n= 28) versus placebo-assigned (n= 29) participants (P= .63). Nasal transcriptomic responses correlated with TNSS, but a treatment effect was not observed. Cockroach serum-specific IgE decreased to a similar extent in both groups, while decreased cockroach skin prick test wheal size was greater among SCIT participants (P= .04). A200-fold increase in cockroach serum-specific IgG4 was observed among subjects receiving SCIT (P< .001) but was unchanged in the placebo group. T-cell IL-4 responses following cockroach allergen stimulation decreased to a greater extent among SCIT versus placebo (P= .002), while no effect was observed for IL-10 or IFN-γ. A year of SCIT failed to alter NAC TNSS and nasal transcriptome responses to cockroach allergen challenge despite systemic effects on allergen-specific skin tests, induction of serum-specific IgG4 serum production and down-modulation of allergen-stimulated T-cell responses.

Gamma Irradiated Pasteurella multocida Vaccine induces strong humoral immunity and protects rabbits from disease

Pasteurella multocida is affecting a multitude of animals and severely affects livestock production. Existing vaccines are mostly chemically inactivated and do not lead to wide protection. Irradiated vaccines are enjoying a renaissance and the concept of “replication defficient but metabolically active” vaccines was recently evaluated in several vaccine trials. P. multocida was isolated from the nasal swab, blood, and lung swab samples from infected rabbits. Gamma irradiation of P. multocida for inhibition of replication was evaluated at an optimized irradiation dose of 10 Kgy established. Four groups of rabbits were (mock) vaccinated with a commercial P. multocida vaccine and three irradiated formulations as liquid, lyophilized formulations with added Trehalose and lyophilized-Trehalose with an “activation” culturing the irradiated bacteria for 24 in broth. Evaluation of humoral immune response by ELISA showed that all three irradiated vaccines produced an effective, protective, and continued IgG serum level after vaccination and bacterial challenge. The IFN-γ expression is maintained at a normal level, within each individual group however, the lyophilized trehalose irradiated vaccine showed peak mean of IFN-γ titer at one week after booster dose (day 21) which was statistically significant. Cumulatively, the results of this study show that gamma-irradiated P. multocida vaccines are safe and protect rabbits against disease. Moreover, Rabbits’ immunization with the three irradiated formulations avoided adverse side effects as compared to commercial polyvalent vaccine, the body weight gain for the irradiated vaccine groups indicates less stress compared to the commercial polyvalent vaccine.

PSVI-13 Formulated botanical preparation improves passive immunity from sows to piglets

Abstract The medicinal plant turmeric increases immunoglobulin production in livestock and rodents. The purpose of this investigation was to determine the effect of a formulated blend of turmeric, capsicum, and black pepper oleoresins (TCB) on colostrum and milk quality of sows and health of piglets. Twenty-four sows (Parity 2+) were assigned to one of the following dietary treatments (n = 8 sows/treatment): 1) unsupplemented control (CON); 2) 100 ppm of TCB (TCB-100), and 3) 150 ppm of TCB (TCB-150). Supplementation was from 87 d of gestation until weaning (d 28). During gestation and lactation, individually housed sows were fed fortified corn and soybean meal diets at 2.5 kg/d and 2.5 + 0.25 * piglet kg/d, respectively, with ad libitum access to water. Blood and colostrum samples were collected from the sow within 24 h of farrowing for IgG and IgA analysis, and milk samples were collected weekly for IgA analysis. Piglet blood samples were collected at weaning (d 28) for IgG and IgA analysis and at 4-wk post weaning for IgA analysis. Data were subjected to a one-way ANOVA (or two-way in the case of repeated measures), with tests for linear trend of the dose response. Serum IgG and IgA in sows at farrowing were linearly increased with TCB supplementation (Table). Similarly, colostrum IgG, and colostrum and milk IgA were linearly increased with TCB, with greatest concentration in TCB-150 relative to CON (Table). Serum IgG in piglets was not affected by sow supplementation, but serum IgA was linearly increased. Interestingly, the increase in serum IgA persisted through 4-wk post-weaning. Diarrhea frequency in piglets 1 to 4 wk post-weaning was linearly decreased with TCB supplementation (Table). A follow-up study with a similar design was conducted with supplementation of TCB-150 starting at 108 d of gestation to represent a commercial application in lactating diets only. Sow serum IgG and IgA at farrowing were measured, and both were significantly increased with TCB-150 (Table). In conclusion, supplementation of TCB at 150 ppm improves colostrum and milk quality, and passive immunity from sows to piglets. Furthermore, enteric health of the piglets was improved. Additional experiments to determine the implications of this response on sow and piglet health and performance in commercial conditions are warranted.

Study on the effects of toosendanin against Eimeria tenella and its impact on the apoptosis of cecal cells in chicks

To investigate the therapeutic effect of toosendanin (TSN) against Eimeria tenella (E. tenella) in chicks. In this experiment, a chick model of artificially induced E. tenella infection was established. The anti-coccidial effect was investigated by treating different doses of TSN. A preliminary mechanism of action was conducted, using cecal cell apoptosis as a starting point. TSN at the concentration of 5 mg/kg BW showed the best effect against E. tenella with the ACI value of 164.35. In addition, TSN reduced pathological damage to cecal tissue, increased the secretion of glycogen and mucus in cecal mucosa, and enhanced the mucosal protective effect. It also elevated the levels of IFN-γ, IL-2, and IgG in serum, and raised the sIgA content in cecal tissue of infected chicks, thereby improving overall immune function. TSN was observed to promote the apoptosis of cecum tissue cells by TUNEL staining analysis. Immunohistochemistry analysis revealed that in TSN-treated groups, the expression of Caspase-3 and Bax was elevated, while the expression of Bcl-2 was reduced. TSN induced apoptosis in host cells by dose-dependently decreasing the Bcl-2/Bax ratio and upregulating Caspase-3 expression. In summary, TSN exhibited significant anticoccidial efficacy by facilitating apoptosis in host cecal cells, with the most pronounced effect observed at a dosage of 5 mg/kg body weight.

Identification of relapse predictors of IgG&lt;sub&gt;4&lt;/sub&gt;-related sclerosing cholangitis

Introduction. Relapses occur in 30–50% of patients IgG4-related sclerosing cholangitis. Relapses may act an independent risk factor for malignancy development and the need in maintenance therapy for relapse prevention is still uncertain. Thus, studying relapse predictors and developing reliable preventive approaches is an important area of research for this condition.Aim. To determine relapse predictors of IgG4-related sclerosing cholangitis.Materials and methods. A single- center dynamic bidirectional observational study was conducted in patients aged 18 years and older with verified IgG4-related sclerosing cholangitis (n = 32). We searched for possible factors influencing the relapse of IgG4- related sclerosing cholangitis. The development of a prognostic model for the relapse probability was carried out using logistic regression. ROC analysis was used to assess the diagnostic performance of quantitative variables in predicting of relapse.Results. The median follow-up period was 33 (16–60) months. The majority of patients with IgG4-related sclerosing cholan- gitis were male (71.9%), median age was 59 ± 13 years. In most patients, delayed diagnosis (median 10.5 [4.8; 22.5] months) was associated with overdiagnosis of primary sclerosing cholangitis (41.2%) or bile duct malignancy (43.8%). Surgical interventions were performed in 50% of patients. Median serum IgG4 level was 2.70 g/L [1.92; 6.48], and 21.9% of patients had normal serum IgG4 level. Disease relapse developed in 34.4% (n = 11) of patients. Serum IgG4 level before glucocorticosteroid therapy ≥ 2.24 g/L and a delay in diagnosis by ≥ 17 months were associated with the relapse (p = 0.040 and p = 0.049 respectively). Multi-organ involvement, and extrahepatic localization of biliary strictures in the patients with the history of surgical interventions increased the risk of relapse 85 (p = 0.001) and 12 (p = 0.047) fold, respectively. The presence of biliary strictures below the confluence reduced the risk of relapse 7.5 fold (p = 0.032).Conclusions. Possible predictors of IgG4-related sclerosing cholangitis relapse may include multi- organ involvement, intrahepatic and proximal extrahepatic strictures, prior surgical interventions in patients with extrahepatic strictures, high serum IgG4 level, and delayed diagnosis.