Serum IgG Levels Research Articles

In vivo mRNA expression of a multi-mechanistic mAb combination protects against Staphylococcus aureus infection

Single monoclonal antibodies (mAbs) can be expressed in vivo through gene delivery of their mRNA formulated with liponanoparticles (mRNA/LNP). However, delivery of a mAb combination could be challenging due to risk of heavy and light variable chain mispairing. We evaluated the pharmacokinetics of a three mAb combination against Staphylococcus aureus first in single chain variable fragment scFv-Fc and then in immunoglobulin G 1 (IgG1) format in mice. Intravenous delivery of each mRNA/LNP or the trio (1 mg/kg each) induced functional antibody expression after 24 hours (10-100 μg/ml) with 64 to 78% cognate-chain paired IgG expression after 3 days, and an absence of non-cognate chain pairing for scFv-Fc. We did not observe reduced neutralizing activity for each mAb compared to the level of expression of chain-paired mAbs. Delivery of the trio mRNA protected mice in a S. aureus induced dermonecrosis model. Intravenous administration of the three mRNA in non-human primates achieved peak serum IgG levels ranging between 2.9-13.7 μg/ml with a half-life of 11.8-15.4 days. These results suggest nucleic acid delivery of mAb combinations holds promise and may be a viable option to streamline development of therapeutic antibodies.

Serum inflammatory cytokine IL-4 and IL-18 Levels in Patients with Typhoid Fever in Baghdad

Background: Gram-negative Salmonella enterica serotype typhi, or S. typhi, is intracellular bacteria belong to Enterobacteriaceae family that infect humans and cause Salmonellosis (typhoid fever), or (enteric fever), this disease is a major public health problem and a life-threatening bacterial infection in developing countries. Every year, there are thought to be between 12 and 33 million cases of typhoid fever, which leads to over 600,000 deaths. Specific immunity both humoral and cellular specific immune response activated to control Salmonella infection. This study aimed evaluate the function of IL-4 and IL18 levels as a diagnostic aid for this infection. Material and methods: Ninety suspected patients with typhoid fever diagnosed by specialist according to sign and symptom and thirty apparently healthy control where enrolled during the study period from September 2023 to February 2024. Blood was taken from both groups (5ml) and serum were gathered using centrifugation (3000 rpm for 5 min) and kept frozen in three Eppendorf for detection of serum IgM, IgG, IL-4 and IL-18 levels. Results: the result showed that out of 90 blood samples only 60 samples were positive to salmonella infection (confirmed by detecting specific salmonella IgM and IgG antibodies using ELIZA kits Sunlong biotech\China). Serum levels of IL-4, and IL18 (pg/ml) was measured in positive samples using ELIZA kits (Cloud-clone corp \USA). There is a significant increase in the level of IgM (0.33 ± 0.13) (mg\dl) and IgG (0.27 ± 0.1) (mg\dl) as compared to the control group in patients (0.16±0.03 and 0.12±0.03) (mg\dl) respectively with P < 0.01, and there was a significant increase in the average IL-4 (334.00 ± 87.49) (pg/ml) and IL-18 level in patients (380.44 ± 68.95) (pg/ml) compared to the control group (83.40 ± 17.44 and 189.66 ± 70.40) (pg/ml) respectively with P < 0.001. The results indicated a direct correlation between IL-4 and IL-18 serum levels with high level of serum IgM antibody compared to their levels in control group.

Fermented Astragalus Powder, a New Potential Feed Additive for Broilers to Improve the Growth Performance and Health.

A total of 320 1-day-old broilers were randomly divided into five groups. The control group (CON) received a basal diet, while the FAP4, FAP2, and FAP1 groups were provided with the basal diet supplemented with 4%, 2%, and 1% fermented Astragalus powder, respectively. The unfermented Astragalus powder (UAP2) group was fed the basal diet supplemented with 2% UAP. Each group contained eight replicates of eight chicks each. The results revealed that the final BW and ADG in the FAP 1 and FAP2 were higher than those in the UAP2 and CON groups, while reducing F/G from day 14 to day 42. On day 42, the thymus index in the UAP and FAP groups as well as the bursa index in the FAP4 group showed significant increases compared to those in the CON group. Supplementation with 2% FAP elevated serum IgA levels in broilers on day 28 and day 42, and it also increased serum IgG levels on day 42. Furthermore, supplementation with 2% FAP elevated serum albumin (ALB) levels in broilers, while supplementation with 4% FAP increased serum (glucose) GLU levels in broilers on day 28. The serum biochemical parameters and pathological observation of the liver and kidney in the groups did not show any adverse effects on broilers' health. In addition, the serum total antioxidant capacity (T-AOC) level significantly increased in the FAP4 and FAP2 groups on day 28, and the malondialdehyde (MDA) level in both serum and liver tissue decreased in the FAP2 group on day 28 and day 42. Compared to the CON group, 2% FAP and 2% UAP supplementation reduced the relative abundance of Bacteroides and supplementation with 2% FAP increased the relative abundance of Alistipes on day 42. In conclusion, the dietary supplementation of FAP can enhance the growth performance, immune function, and antioxidant capacity and regulate microflora in broilers, of which 2% FAP is more effective. It indicates FAP exhibits significant application potential as a promising feed additive for broilers.

A machine learning-based diagnosis modeling of IgG4 Hashimoto's thyroiditis.

This study aims to develop a non-invasive diagnosis model using machine learning (ML) for identifying high-risk IgG4 Hashimoto's thyroiditis (HT) patients. A retrospective cohort of 93 HT patients and a prospective cohort of 179 HT patients were collected. According to the immunohistochemical and pathological results, the patients were divided into IgG4 HT group and non-IgG4 HT group. Serum TgAb IgG4 and TPOAb IgG4 were detected by ELISAs. A logistic regression model, support vector machine (SVM) and random forest (RF) were used to establish a clinical diagnosis model for IgG4 HT. Among these 272 patients, 40 (14.7%) were diagnosed with IgG4 HT. Patients with IgG4 HT were younger than those with non-IgG4 HT (P < 0.05). Serum levels of TgAb IgG4 and TPOAb IgG4 in IgG4 HT group were significantly higher than those in non-IgG4 HT group (P < 0.05). There were no significant differences in gender, disease duration, goiter, preoperative thyroid function status, preoperative TgAb or TPOAb levels, and thyroid ultrasound characteristics between the two groups (all P > 0.05). The accuracy, sensitivity, and specificity were 57%, 78%, and 79% for logistic regression model of IgG4 HT, 80 ± 7%, 84.7% ± 2.6%, and 75.4% ± 9.6% for the RF model and 78 ± 5%, 89.8% ± 5.7%, and 64.7% ± 5.7% for the SVM model. The RF model works better than SVM. The area under the ROC curve of RF ranged 0.87 to 0.92. A clinical diagnosis model for IgG4 HT established by RF model might help the early recognition of the high-risk patients of IgG4 HT.

Effects of alpha-lipoic acid on the growth performance and serum biochemical index values of puppies

We investigated the effects of alpha-lipoic acid (α-LA) on the growth performance and health level of puppies. A total of 16 healthy Chinese rural dogs aged 30–45 days were randomly divided into four groups: control group (CG), low-dose group (LDG), middle-dose group (MDG) and high-dose group (HDG). The puppies were fed fresh food supplemented with 0, 0.2, 0.4 and 0.6 g/kg of α-LA, respectively. Average daily feed intake (ADFI), average daily gain (ADG), feed-to-gain ratio (F/G), faecal score, intestinal absorption function and serological indices on days 1, 14 and 28 were determined and analysed. The trial period was 28 days. The following results were obtained: (1) α-LA supplementation at 0.4 and 0.6 g/kg significantly increased the ADFI and ADG of the puppies (P < 0.05) but had no significant effect on the faecal score (P > 0.05); (2) α-LA in the fresh diet significantly increased crude fat (EE) digestibility (P< 0.05) but significantly decreased calcium (Ca) digestibility (P< 0.05), without significant impacts on the digestibility of nutrients such as crude protein (CP) and total phosphorus (P); (3) with increasing α-LA inclusion levels, the content of D-xylose in the blood serum increased, but there was no significant difference among groups (P = 0.097). Adding 0.6 mg/kg α-LA to the fresh diet significantly increased the content of IgG in the serum after 14 and 28 days (P < 0.05). At 28 days, adding 0.4 and 0.6 g/kg α-LA to the fresh diet could significantly increase the contents of albumin (ALB) and total protein (TP) in the blood serum (P < 0.05), and the addition of 0.6 g/kg α-LA could significantly increase the serum levels of IgA and IgG (P < 0.05). The addition of α-LA significantly increased the activities of total antioxidant capacity (T-AOC), glutathione peroxidase (GSH-Px) and total superoxide dismutase (T-SOD) (P < 0.05), decreased the content of malondialdehyde (MDA) (P < 0.05), decreased the levels of interleukin-1β (IL-1β) and interleukin-6 (IL-6) (P< 0.05) and increased the content of interleukin-10 (IL-10) in the blood serum (P < 0.05). In conclusion, the addition of α-LA at 0.6 g/kg to the fresh diet of puppies can improve the ADFI, ADG, serum immune capacity, antioxidant capacity and anti-inflammatory capacity of puppies.

Protective Efficacy of a Novel DNA Vaccine with a CL264 Molecular Adjuvant against Toxoplasma gondii in a Murine Model.

Toxoplasmosis is a significant global zoonosis with devastating impacts, and an effective vaccine against toxoplasmosis for humans has not yet been developed. In this study, we designed and formulated a novel DNA vaccine encoding the inhibitor of STAT1 transcriptional activity (IST) of T. gondii utilizing the eukaryotic expression vector pEGFP-N1 for the first time, with CL264 being a molecular adjuvant. Following intramuscular injection of the vaccine into mice, the levels of antibodies and cytokines were assessed to evaluate the immune response. Additionally, mice were challenged with highly virulent RH-strain tachyzoites of T. gondii, and their survival time was observed. The results show that the levels of IgG in serum, the ratio of IgG2a/IgG1 and the levels of IFN-γ in splenocytes of mice were significantly higher in the pEGFP-TgIST group and the pEGFP-TgIST + CL264 group than in the control group. In addition, the proportion of CD4+/CD8+ T cells was higher in mice immunized with either the pEGFP-TgIST group (p < 0.001) or the pEGFP-TgIST + CL264 group (p < 0.05) compared to the three control groups. Notably, TgIST-immunized mice exhibited prolonged survival times after T. gondii RH strain infection (p < 0.05). Our findings collectively demonstrate that the TgIST DNA vaccine elicits a significant humoral and cellular immune response and offers partial protection against acute T. gondii infection in the immunized mice, which suggests that TgIST holds potential as a candidate for further development as a DNA vaccine.

The effect of antiphospholipid antibodies on the frequency of extrasystoles in men with coronary heart disease and and myocardial infarction

Abstract Background Coronary heart disease (CHD) is one of the most socially significant diseases of the cardiovascular system. Acute myocardial infarction (MI) develops 10 years earlier in men than in women. Manifestation of MI in young men quite often happen without clinically significant stenosis of coronary vessels. And fatal arrhythmias are one of the main causes of death in patient with cardiovascular diseases. Purpose To evaluate the clinical and pathogenetic significance of antiphospholipid antibodies (aPL) in patients with MI and disorders of rythm. Methods 107 patients men (average age 51.2 ± 6.15 years) with CHD and MI were examined. The content of aPL IgG - antibodies to cardiolipin, phosphatidylserine, phosphatidylinositol, phosphatidylacetate in the blood serum were determined by enzyme-linked immunosorbent assay and electrocardiography Holter monitor 24 hours tests were done. Results aPL IgG were detected in 56 patients (52,3% of the total number of patients with MI), it concentration threshold 10 GPL U/ml in blood serum. The median age of first acute MI in men 56 years, according to the literary data. In our investigation average age of aPL positive patients is 44.8 ± 5.47 years. They had first MI on average 12 years earlier than general population. The level of aPL IgG in blood serum was higher in 1,7 times (19,3 ± 7,32 GPL U/ml and 11,4 ± 5,41 GPL U/ml (p &amp;lt;0.05) in patients with recurrent MI compared to one MI. Also the results of the study showed that the highest prevalence of polytopic extrasystoles is observed among aPL positive CHD patients with recurrent MI (68,3%) compared to one MI in anamnesis (26,3%). Moreover, 23.2% of people who had recurrent MI had ventricular extrasystole of high gradations. It is important to note, that іn patients with first Q-MI levels of aFL IgG were in 1.27 times higher (p&amp;lt;0.05) than in patients with first non-Q-MI. And the frequency of the polytopic extrasystoles was on 38% higher (p&amp;lt;0.01) іn patients with first Q-MI compared to patients with first non-Q-MI. Conclusion The results obtained by us indicate the possible involvement of the autoimmune factor, in particular aPL IgG, in the pathogenesis of CHD. Positive correlation of aPL IgG with the frequency of rhythm disorders indicates the severity of condition in men with CHD and MI in anamnesis and need for further research.

#752 Ponatinib exacerbates renal damage in MRL/lpr lupus model mice through the lipid metabolism pathway

Abstract Background and Aims The role of tyrosine kinase inhibitors (TKIs) in lupus nephritis is controversial. Ponatinib is a third-generation tyrosine kinase inhibitor that targets multiple receptors. This study aims to explore the effect of ponatinib in lupus nephritis, with the hope of providing insights for the clinical application of ponatinib. Method At 8 weeks of age, mice were randomly divided into four groups. One group received no treatment, while the other three groups were respectively administered Ponatinib, prednisolone acetate, and a combination of Ponatinib and prednisolone acetate. The treatment was concluded when the mice reached 16 weeks of age. ELISA was employed to measure the levels of anti-dsDNA IgG, ANA, and C3 in mouse serum. DEGs and DELs were identified using the DESeq2 package in R. Pathway and gene ontology enrichment analyses were performed using the MetaCore database. Results Compared to the negative control, those mice receiving ponatinib showed a significant increase in the urinary protein/creatinine ratio (P &amp;lt; 0.01), along with notable elevations in blood creatinine and blood urea nitrogen. Pathological examination of kidney tissue suggested predominant acute lesions, including transparent thrombi, cellulose-like necrosis, cellular/fibrous crescents, and interstitial inflammation. Interestingly, serum testing in MRL/lpr mice revealed no significant differences in lupus activity-related indicators, including autoantibodies ANA, double-stranded DNA, and complement C3, between the negative control group and the ponatinib group. Furthermore, it was discovered that the kidney damage caused by ponatinib in MRL/lpr mice could be reversed by prednisone. RNA-Seq of kidney tissue from MRL/lpr mice showed a total of 44 differentially expressed genes when comparing the negative control with mice receiving ponatinib, including 23 upregulated and 21 downregulated genes. Pathway analysis revealed that the top four pathways were all related to lipid metabolism. Conclusion Ponatinib significantly exacerbated kidney damage in MRL/lpr mice and did not induce changes in lupus activity.

Lactic acid bacteria and yeast co-fermented milk alleviate cow milk allergy.

Cow milk allergy is one of the common food allergies. Our previous study showed that the allergenicity of fermented milk is lower than that of unfermented skimmed milk in vitro, and the antigenicity of β-lactoglobulin and α-lactalbumin in fermented milk was decreased by 67.54% and 80.49%, respectively. To confirm its effects in vivo, allergic BALB/C mice model was used to further study the allergenicity of fermented milk. It was found that compared with the skim milk (SM) group, the intragastrically sensitization with fermented milk had no obvious allergic symptoms and the fingers were more stable: lower levels of IgE, IgG, and IgA in serum, lower levels of plasma histamine and mast cell protein-1, and immune balance of Th1/Th2 and Treg/Th17. At the same time, intragastrically sensitization with fermented milk increased the α diversity of intestinal microbiota and changed the microbiota abundance: the relative abundance of norank-f-Muribaculaceae and Staphylococcus significantly decreased, and the abundance of Lachnospiraceae NK4A136 group, Bacteroides, and Turicibacter increased. In addition, fermented milk can also increase the level of short-chain fatty acids in the intestines of mice. It turns out that fermented milk is much less allergenicity than SM. PRACTICAL APPLICATION: Fermentation provides a theoretical foundation for reducing the allergenicity of milk and dairy products, thereby facilitating the production of low-allergenic dairy products suitable for individuals with milk allergies.

Developing a PmSLP3-based vaccine formulation that provides robust long-lasting protection against hemorrhagic septicemia-causing serogroup B and E strains of Pasteurella multocida in cattle.

Pasteurella multocida is a bacterial pathogen that causes a variety of infections across diverse animal species, with one of the most devastating associated diseases being hemorrhagic septicemia. Outbreaks of hemorrhagic septicemia in cattle and buffaloes are marked by rapid progression and high mortality. These infections have particularly harmful socio-economic impacts on small holder farmers in Africa and Asia who are heavily reliant on a small number of animals kept as a means of subsistence for milk and draft power purposes. A novel vaccine target, PmSLP-3, has been identified on the surface of hemorrhagic septicemia-associated strains of P. multocida and was previously shown to elicit robust protection in cattle against lethal challenge with a serogroup B strain. Here, we further investigate the protective efficacy of this surface lipoprotein, including evaluating the immunogenicity and protection upon formulation with a variety of adjuvants in both mice and cattle. PmSLP-3 formulated with Montanide ISA 61 elicited the highest level of serum and mucosal IgG, elicited long-lasting serum antibodies, and was fully protective against serogroup B challenge. Studies were then performed to identify the minimum number of doses required and the needed protein quantity to maintain protection. Duration studies were performed in cattle, demonstrating sustained serum IgG titres for 3 years after two doses of vaccine and full protection against lethal serogroup B challenge at 7 months after a single vaccine dose. Finally, a serogroup E challenge study was performed, demonstrating that PmSLP-3 vaccine can provide protection against challenge by the two serogroups responsible for hemorrhagic septicemia. Together, these data indicate that PmSLP-3 formulated with Montanide ISA 61 is an immunogenic and protective vaccine against hemorrhagic septicemia-causing P. multocida strains in cattle.

Efficacy and safety of telitacicept therapy in systemic lupus erythematosus with hematological involvement.

To evaluate the efficacy and safety of telitacicept in SLE patients specifically with hematological involvement. A total of 22 patients with SLE and hematological involvement were included in this study. These patients received telitacicept in addition to standard therapy. We compared their demographic characteristics, clinical manifestations, and laboratory indicators before and after the administration of telitacicept. A total of 22 patients received telitacicept treatment for a median duration of 10.4months (ranging from 6 to 19months). Following telitacicept therapy, significant improvements were observed in various parameters compared to baseline. Specifically, white blood cell count increased from (3.98 ± 1.80) 109/L to (6.70 ± 2.47) 109/L, (P = 0.002), hemoglobin levels increased from (100 ± 19) g/L to (125 ± 22) g/L, (P < 0.001), and platelet count increased from (83 ± 60) 109/L to (161 ± 81) 109/L, (P = 0.004). SLE Disease Activity Index (SLEDAI) scores decreased from 12(5,15) to 0(0,4), (P < 0.001). Additionally, C3 and C4 levels showed improvement. Telitacicept treatment also resulted in a significant reduction in serum IgG levels and daily prednisone dosage. Only one adverse event (4.5%) was reported during the treatment, which was a urinary tract infection. The combination of telitacicept and standard treatment demonstrated significant improvements in anemia, as well as increased leukocyte and platelet levels in patients with SLE and hematological involvement. Importantly, the observed adverse events were manageable and controllable. Key Points • Telitacicept effectively improves anemia, clinical outcomes, and increases leukocyte and platelet counts. • Treatment with telitacicept leads to decreased levels of lgG, IgA, anti-dsDNA, and SLEDAI scores, while serum complement C3 and C4 returned to normal. • During the follow-up period there were observed changes in individual parameters, clinical symptoms, and organ involvement, all without significant adverse events.

Probiotic-derived amphiphilic exopolysaccharide self-assembling adjuvant delivery platform for enhancing immune responses

Enhancing immune response activation through the synergy of effective antigen delivery and immune enhancement using natural, biodegradable materials with immune-adjuvant capabilities is challenging. Here, we present NAPSL.p that can activate the Toll-like receptor 4 (TLR4) pathway, an amphiphilic exopolysaccharide, as a potential self-assembly adjuvant delivery platform. Its molecular structure and unique properties exhibited remarkable self-assembly, forming a homogeneous nanovaccine with ovalbumin (OVA) as the model antigen. When used as an adjuvant, NAPSL.p significantly increased OVA uptake by dendritic cells. In vivo imaging revealed prolonged pharmacokinetics of NAPSL. p-delivered OVA compared to OVA alone. Notably, NAPSL.p induced elevated levels of specific serum IgG and isotype titers, enhancing rejection of B16-OVA melanoma xenografts in vaccinated mice. Additionally, NAPSL.p formulation improved therapeutic effects, inhibiting tumor growth, and increasing animal survival rates. The nanovaccine elicited CD4+ and CD8+ T cell-based immune responses, demonstrating the potential for melanoma prevention. Furthermore, NAPSL.p-based vaccination showed stronger protective effects against influenza compared to Al (OH)3 adjuvant. Our findings suggest NAPSL.p as a promising, natural self-adjuvanting delivery platform to enhance vaccine design across applications.

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.

The role of M1/M2 macrophage polarization in primary Sjogren’s syndrome

BackgroundThe purpose of this study was to investigate the role of macrophage polarization in the pathogenesis of primary Sjogren’s syndrome (pSS).MethodsPeripheral venous blood samples were collected from 30 patients with pSS and 30 healthy controls. Minor salivary gland samples were abtainted from 10 of these patients and 10 non-pSS controls whose minor salivary gland didn’t fulfill the classification criteria for pSS. Enzyme-linked immuno sorbent assay was used to examine the serum concentration of M1/M2 macrophage related cytokines (TNF-a, IL-6, IL-23, IL-4, IL-10 and TGF-β). Flow cytometry was used to examine the numbers of CD86+ M1 macrophages and CD206+ M2 macrophages in peripheral blood mononuclear cells (PBMCs). Immunofluorescence was used to test the infiltration of macrophages in minor salivary glands.ResultsThis study observed a significant increase in pSS patients both in the numbers of M1 macrophages in peripheral blood and serum levels of M1-related pro-inflammatory cytokines (IL-6, IL-23 and TNF-α). Conversely, M2 macrophages were downregulated in the peripheral blood of pSS patients. Similarly, in the minor salivary glands of pSS patients, the expression of M1 macrophages was increased, and that of M2 macrophages was decreased. Furthermore, a significantly positive correlation was found between the proportions of M1 macrophages in PBMCs and serum levels of IgG and RF.ConclusionsThis study reveals the presence of an significant imbalance in M1/M2 macrophages in pSS patients. The M1 polarization of macrophages may play an central role in the pathogenesis of pSS.

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.

Autoimmune hepatitis displays distinctively high multi-antennary sialylation on plasma N-glycans compared to other liver diseases

BackgroundChanges in plasma protein glycosylation are known to functionally affect proteins and to associate with liver diseases, including cirrhosis and hepatocellular carcinoma. Autoimmune hepatitis (AIH) is a liver disease characterized by liver inflammation and raised serum levels of IgG, and is difficult to distinguish from other liver diseases. The aim of this study was to examine plasma and IgG-specific N-glycosylation in AIH and compare it with healthy controls and other liver diseases.MethodsIn this cross-sectional cohort study, total plasma N-glycosylation and IgG Fc glycosylation analysis was performed by mass spectrometry for 66 AIH patients, 60 age- and sex-matched healthy controls, 31 primary biliary cholangitis patients, 10 primary sclerosing cholangitis patients, 30 non-alcoholic fatty liver disease patients and 74 patients with viral or alcoholic hepatitis. A total of 121 glycans were quantified per individual. Associations between glycosylation traits and AIH were investigated as compared to healthy controls and other liver diseases.ResultsGlycan traits bisection (OR: 3.78 [1.88–9.35], p-value: 5.88 × 10− 3), tetraantennary sialylation per galactose (A4GS) (OR: 2.88 [1.75–5.16], p-value: 1.63 × 10− 3), IgG1 galactosylation (OR: 0.35 [0.2–0.58], p-value: 3.47 × 10− 5) and hybrid type glycans (OR: 2.73 [1.67–4.89], p-value: 2.31 × 10− 3) were found as discriminators between AIH and healthy controls. High A4GS differentiated AIH from other liver diseases, while bisection associated with cirrhosis severity.ConclusionsCompared to other liver diseases, AIH shows distinctively high A4GS levels in plasma, with potential implications on glycoprotein function and clearance. Plasma-derived glycosylation has potential to be used as a diagnostic marker for AIH in the future. This may alleviate the need for a liver biopsy at diagnosis. Glycosidic changes should be investigated further in longitudinal studies and may be used for diagnostic and monitoring purposes in the future.

COVID-19 and the flu: clinical and immunological features in children

In conditions of co-circulation of COVID-19 pathogens and other acute respiratory infections, the risk of simultaneous infection with SARS-CoV-2 and other pathogens, in particular influenza viruses, increases. Previously published data on the mutual influence of such combined infectious processes are very contradictory.Purpose. To determine the clinical and immunological features of the combined course of COVID-19 and influenza in children.Material and methods. Among 3,983 hospitalized children with COVID-19, 48 patients (1.2%) co-infected with influenza A and B viruses were identified by PCR. 31 children with a combination of COVID-19/Influenza were subjected to in-depth examination. The comparison group consisted of 30 children with SARS-CoV-2 monoinfection. In addition to standard physical, instrumental and laboratory studies, serum levels of IgM and IgG to SARS-CoV-2 S protein were determined in patients of the compared groups using ELISA.Results. In children with a combination of influenza and infection caused by both delta and omicron variants of SARS-CoV-2, acute bronchitis was more common, regardless of age, compared with patients with SARS-CoV-2 monoinfection. Co-infection with the influenza virus did not change the incidence of pneumonia in patients with omicron-SARS-CoV-2 infection, and in patients with delta-SARS-CoV-2 infection it decreased it. In co-infected children, the severity of intoxication syndrome and the level of D-dimer in the blood were higher. In addition, patients with a combination of COVID-19 and influenza showed lower concentrations of IgM and IgG to S-protein in comparison with patients with SARS-CoV-2 monoinfection.Conclusion. Co-infection with influenza viruses alters the clinical course of COVID-19, while the nature and vector of changes depend on the SARS-CoV-2 gene variant. A decrease in the severity of the humoral immune response to SARS-CoV-2 in co-infected children was found.

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.

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.