Serum IgA Levels Research Articles

Effects of increasing levels of rubber seed cake on growth performance, nutrient digestion metabolism, serum biochemical parameters, and rumen microbiota of Hu sheep

This study aimed to reveal the effects of increasing levels of rubber seed cake (RSC) on growth performance, nutrient digestion metabolism, serum biochemical parameters, and rumen microbiota in Hu sheep. In this study, 48 Hu sheep, weighing 17.01 ± 0.57 kg at 3 months of age, were randomly divided into four treatments: 0% rubber seed cake (RSC0%), 6% rubber seed cake (RSC6%), 12% rubber seed cake (RSC12%) and 18% rubber seed cake (RSC18%), with 12 sheep per group. Compared to the RSC0%, the ADG and DMI of the RSC6% and RSC12% were increased (P > 0.05). The apparent digestibility of OM and EE quadratically (P < 0.05) changed with the increase of RSC supplementation, with the greatest apparent digestibility of OM and EE observed in the RSC6% diet. With increased RSC supplementation, the N intake and fecal N increased linearly (P < 0.05), and the apparent digestibility of N reduced linearly (P < 0.05). As the increase of RSC supplementation, the serum levels of IgA, IgM, IgG, IL-4, T-AOC, and GSH-Px increased linearly (P < 0.05), and the serum level of IL-6 reduced linearly (P < 0.05). The serum level of IL-1β reduced quadratically (P < 0.05) with the increased RSC dose, and the serum level of SOD increased quadratically (P < 0.05) with the increased RSC dose. The ruminal NH3-N and the relative abundance of norank_Muribaculaceae quadratically (P < 0.05) changed with increased RSC supplementation, and the greatest relative abundance of norank_Muribaculaceae was observed in the RSC6% diet. In general, incorporating RSC into the diet of Hu sheep did not adversely affect growth performance and rumen fermentation characteristics. Supplementing with 6% RSC enhanced the relative abundance of norank_Muribaculacea in the rumen fluid and the immune and antioxidant capabilities. However, supplementing with 12 and 18% RSC might have negatively impacted nutrient digestion and metabolism. Therefore, this study recommended replacing corn and soybean meal with 6% RSC in the diet of Hu sheep.

Safety and immunogenicity in humans of enterotoxigenic Escherichia coli double mutant heat-labile toxin administered intradermally

Enterotoxigenic Escherichia coli (ETEC) diarrhea is associated with a high burden of disease globally, for which no licensed vaccine is available. A Phase 1, double-blind, dose-escalation (0.1-2.0 µg) study was conducted to evaluate the safety and immunogenicity of double mutant heat-labile toxin LTR192G/L211A (dmLT) delivered intradermally (ID) to healthy adults. Subjects received up to three immunizations at three-week intervals. The vaccine was safe, although it induced mild local and some gastrointestinal adverse events, as well as frequent hyperpigmentation at the injection site. High levels of serum IgG and IgA, LT neutralizing antibodies, and IgG and IgA antibodies in lymphocyte supernatant were elicited post-vaccination, most prominently at the largest dose (2.0 μg). Rates of responses were the highest in subjects who received the largest dose (2.0 μg) and multiple immunizations. The ETEC dmLT vaccine was safe and highly immunogenic, inducing long-lasting systemic and mucosal responses when administered by the ID route. Trial registration Clinical Trials NCT02531685.

Dietary incorporation of biological curcumin nanoparticles improved growth performance, ileal architecture, antioxidative status, serum lipid profile, and humoral immune response of heat-stressed broiler chickens.

Heat stress greatly impairs poultry productivity, underscoring the urgent need for effective strategies to mitigate these adverse effects and improve overall poultry health. This study assessed the impact of dietary curcumin nanoparticles (CurNPs) on blood metabolites, immunity, redox status, ileal histomorphometry, and growth of broilers subjected to heat stress. A total of 400 one-day-old Ross-308 broiler chicks were randomly distributed into five groups, each consisting of eight replicates with ten birds per replicate. The chicks were fed a basal diet containing CurNPs at concentrations of 0, 100, 200, 300, or 400 mg/kg feed, designated as 0CurNPs, 100CurNPs, 200CurNPs, 300CurNPs, and 400CurNPs, respectively. Dietary CurNPs supplementation linearly (P > 0.001) improved weight gain, feed conversion ratio and European production efficiency index, while feed intake decreased linearly (P > 0.001) with increasing CurNPs supplementation. Carcass traits and serum renal and hepatic function biomarkers remained unaffected by the treatment. Serum cholesterol and LDL levels exhibited linear and quadratic (P > 0.05) reduction in all treated groups, although triglycerides and VLDL levels reduced linearly (P > 0.05) only in the 300CurNPs group. The inclusion of CurNPs resulted in a linear and quadratic increase (P > 0.05) in ileal villi height and a linear elevation (P > 0.05) in the villi height-to-crypt depth ratio. The redox status was improved with CurNPs supplementation, as serum MDA levels showed a linear decrease (P > 0.05) in the 300CurNPs and 400CurNPs groups, while SOD levels increased linearly and quadratically (P > 0.05) across all treated groups. Furthermore, dietary CurNPs exhibited linear (P > 0.001) increases in serum levels of IgM, IgG, and IgA, though antibody titres against NDV and AIV were unaffected. In conclusion, CurNPs proved to be an effective growth promoter, enhancing growth, intestinal architecture, redox status, and humoral immunity in heat-stressed broilers.

Comparative analysis of the performance, egg quality and ovarian immune function of fast and slow feather strains in tianfu green shell laying hens at various stages of egg production.

This objective of this experiment was to compare and evaluate the performance, egg quality, and immune function of Tianfu green shell laying hens with varying feather growth rates, in order to provide a reference for their rational utilization. A total of 120 one-day-old healthy Tianfu green shell laying hens were classified into the early-feathering (EF) and late-feathering (LF) groups through phenotypic identification of feather length and qPCR molecular identification. Each group was subdivided into four replicates, with 30 chickens in each replicate. Under the identical feeding and management conditions, the live weight, tibial length, egg production performance, egg quality, serum biochemical indexes, immune protein content, and the expression of related genes in uterine and ovarian tissues were assessed and analyzed. The results indicated that LF hens exhibited significantly greater live weights at 4, 16, 27, and 43 weeks (P < 0.05) and longer tibia lengths at 4 and 16 weeks (P < 0.05) compared to EF hens, suggesting enhanced early growth performance. Conversely, EF hens demonstrated superior egg-laying performance, characterized by a higher laying rate during both peak (27 weeks) and late (43 weeks) laying periods (P < 0.05), despite their eggs being lighter in weight (P < 0.05). Furthermore, EF hens exhibited the production of eggs with significantly thicker and stronger shells during the peak laying period (P < 0.05), while no notable differences were observed in other egg quality parameters. Immunologically, EF hens demonstrated elevated peak serum levels of IgA, IgG, and IgM compared to LF hens. Additionally, the expression levels of IFN-γ and interleukin 6 (IL-6) genes in the ovaries were markedly higher in EF hens. These findings indicate that although LF hens excel in early growth stages, EF hens exhibit superior egg production capabilities and enhanced immune responses.

The Changes of Lymphocytes and Immune Molecules in Irradiated Mice by Different Doses of Radiation.

The effects of different radiation doses on T and B lymphocyte functional subsets and the changes of immune cells and immune molecules were observed in mice at different times post-irradiation to provide a theoretical basis for the changes of immune cells affected by radiation. In this study, the changes of T and B immune cells and immune-related molecules were observed at 1, 3, 7, 14, and 21 d after single irradiation of 2 Gy, 4 Gy, and 6 Gy. The results showed that white blood cells (WBC), lymphocytes (LYMPH), and lymphocyte percentage (LYMPH%) in peripheral blood of mice were significantly reduced and reached the lowest point 3 d after irradiation. Flow cytometry results showed that the percentages of CD3+T and CD8+/CD3+T lymphocytes in spleen and thymus were significantly decreased, and the percentages of CD19+B lymphocytes in spleen and CD4+/CD3+T lymphocytes in thymus were also decreased. However, the percentages of splenic NK cells, CD4+/CD3+T cells, and CD4+/CD8+ ratios in spleen and thymus were increased. Most of the indicators fell to the lowest or highest point 3 d after irradiation, indicating that immune function was suppressed at this time. From 7 to 21 d after irradiation, most immune cells gradually recovered. Single irradiation of 2 Gy, 4 Gy, and 6 Gy increased the contents of IL-1β, IL-2, IL-6, IL-17, TNF-α, TGF-β, and IFN-γ in serum of mice and decreased the contents of anti-inflammatory factors IL-4 and IL-10. The serum levels of immunoglobulin IgA, IgG, IgM and complement C3, C4 were significantly increased after irradiation. Our study showed that a single dose of 2 Gy, 4 Gy, and 6 Gy induced immunosuppression in mice, and maximum immunosuppression was achieved 3 d after irradiation. At this time, CD19+B lymphocytes were the most sensitive, followed by CD3+T lymphocytes, and NK cells were the most resistant. The radiosensitivity of CD8+/CD3+T lymphocytes was slightly higher than that of CD4+/CD3+T lymphocytes.

Characterization of diabetic kidney disease in 235 patients: clinical and pathological insights with or without concurrent non-diabetic kidney disease

BackgroundThis study aimed to explore the clinical and pathological features of patients with diabetic kidney disease (DKD), with and without non-diabetic kidney disease (NDKD), through a retrospective analysis. The objective was to provide clinical insights for accurate identification.MethodsA retrospective analysis of 235 patients admitted to the Department of Nephrology at Hangzhou Hospital of Traditional Chinese Medicine was conducted between July 2014 and December 2022. These patients underwent renal biopsy and received a pathology-based diagnosis of DKD. They were categorized into the DKD alone group (93 cases) and the DKD + NDKD group (142 cases).ResultsIn the DKD alone group, gender distribution was even, with ages mainly between 50 and 59 years, and a disease duration of less than 5 years, primarily presenting nodular diabetic glomerulosclerosis. In contrast, the DKD + NDKD group had a higher male incidence, a wider age range, longer disease duration, and prevalent diffuse diabetic glomerulosclerosis. Acute and chronic tubulointerstitial lesions and IgA nephropathy were the predominant types of combined NDKD, accounting for 40.14% and 35.21%, respectively. Clinical correlation analysis revealed associations between glomerular grading, tubulointerstitial lesions, renal arteriolar vitelliform lesions, renal vascular atherosclerosis, and clinical parameters such as 24-hour urine protein, hemoglobin, and urinary specific gravity. Multifactorial logistic regression analysis identified independent factors affecting DKD + NDKD, including body mass index, blood creatinine level, microscopic erythrocyte grade, urinary immunoglobulin G/creatinine ratio, and serum immunoglobulin A.ConclusionThe research underscores distinctions in age, gender distribution, disease duration, and renal pathology between DKD alone and DKD + NDKD groups. Additionally, significant discriminative factors including BMI, blood creatinine level, microscopic erythrocyte grade, UIgG/urine creatinine ratio, and serum IgA levels help differentiate DKD from NDKD, thereby enabling personalized treatment approaches. Furthermore, the study highlights the role of RASi as the most commonly used drug in the treatment of both DKD and NDKD, with emerging drugs such as SGLT2 inhibitors showing promising renal protective effects.

Vaccination of mice with Trichinella spiralis C-type lectin elicited the protective immunity and enhanced gut epithelial barrier function.

C-type lectin (CTL) plays an important act in parasite adhesion, host's cell invasion and immune escape. Our previous studies showed that recombinant Trichinella spiralis C-type lectin (rTsCTL) mediated larval invasion of enteral mucosal epithelium. The aim of this study was to investigate protective immunity produced by vaccination with rTsCTL and its effect on gut epithelial barrier function in a mouse model. The ELISA results showed that subcutaneous vaccination of mice with rTsCTL elicited a systemic humoral response (high levels of serum IgG, IgG1/IgG2a and IgA) and significant gut mucosal sIgA responses. The levels of Th1/Th2 cytokines (IFN-γ/IL-4) secreted from spleen, mesenteric lymph nodes and Peyer's patches were distinctly increased at 6 weeks following vaccination (P < 0.05). At one week after challenge, the numbers of goblet cells and expression level of Muc2, Muc5ac and pro-inflammatory cytokines (TNF-α and IL-1β) in gut tissues of vaccinated mice were obviously decreased, while expression of anti-inflammatory cytokines (IL-4 and IL-10) was evidently increased, compared to the infected PBS group. It is interesting that expression levels of gut epithelial tight junctions (TJs; occludin, claudin-1 and E-cad) were prominently elevated and intestinal permeability was interestingly declined in vaccinated mice. The rTsCTL-vaccinated mice exhibited a 51.69 and 48.19% reduction of intestinal adult and muscle larva burdens, respectively. The female fecundity in rTsCTL vaccinated mice was reduced by 40.51%. These findings indicated that rTsCTL vaccination impeded larval invasion and improved gut epithelial integrity and barrier function, reduced worm burdens, and relieved gut and muscle inflammation. Vaccination of mice with rTsCTL elicited an obvious protective immunity against larval challenge, impeded larval invasion of gut mucosa, enhanced gut epithelial integrity and barrier function, reduced worm burdens; it also alleviated gut and muscle inflammation. TsCTL might be a novel candidate target molecule for anti-Trichinella vaccines.

Dietary fermented mixed ingredient product enhances growth performance and intestinal stem cell-mediated epithelial regeneration through Wnt/β-catenin pathway in layer chicks.

This study aimed to investigate the effects of dietary supplements of fermented mixed ingredient product (FMIP) on the growth performance, intestinal health, and immune performance of layer hens during the brooding period. Four hundred eighty healthy one-day-old layer chicks were randomly divided into four groups (six replicates/group, twenty hens/replicate) and were fed with different experimental diets for eight weeks (from day 1 to day 56): (1) Corn-soybean-base diet (CON); (2) Chlortetracycline group (CTC; CON diet supplemented with 0.5g/kg chlortetracycline); (3) 4 % fermented mixed ingredient product (4 % FMIP); (4) 8 % fermented mixed ingredient product (8 % FMIP). The results showed that, compared with the CON group, feeding with CTC, 4 % or 8 % FMIP increased the average daily feed intake (ADFI), average daily gain (ADG), immune organs index, serum IgA, IgM, and IgG levels, as well as the apparent metabolic rates of dry matter, crude protein, crude fiber, and crude ash (P < 0.05). Meanwhile, FMIP supplementation improved jejunal morphology and barrier function, as reflected by increased villus height and transepithelial electrical resistance, decreased DAO activity in serum, and up-regulated Occludin protein expression (P < 0.05). Additionally, FMIP supplementation significantly increased protein expression of the stem cell markers (SOX9 and Lgr5), proliferative cell marker (PCNA), and differentiated absorptive cell marker (Villin) (P < 0.05). The immunofluorescence results were consistent with the above results, and FMIP groups have the same effects as the CTC group. Furthermore, the CTC or 4 % FMIP treatment group resulted in a remarkable increase in Wnt/β-catenin signaling proteins (including β-catenin, TCF4, c-Myc, and Cyclin-D1) compared with the CON group (P < 0.05). In conclusion, dietary supplementation of 4 % FMIP improves growth and immune performance, and promotes the intestinal stem cell expansion of layer chicks through Wnt/β-catenin pathway activation.

Dietary fiber pectin alters the gut microbiota and diminishes the inflammatory immune responses in an experimental peach allergy mouse model.

Since therapeutic options are limited the utilization of prebiotics is suggested to prevent food allergies (FAs). Using an experimental peach allergy model we explored the effect of dietary fiber pectin, a high-methoxyl heteropolysaccharide, on the manifestation of FA. CBA/J mice were sensitized, subsequently orally boosted and provoked with peach peel extract. For dietary intervention, mice were fed a pectin containing diet before (primary-preventive) or after (secondary-preventive) sensitization. Non-treated allergic and sham-treated mice were fed a diet containing 20% cellulose. Fecal microbiota, humoral and intestinal immune cell responses were analyzed. Pectin remarkably affected the gut microbiota composition and diversity, promoting mainly the growth of Bacteroides. The frequency of mast cells, macrophages, and CD3+T cells in the lamina propria of the small intestine was reduced, whereas the frequency of B cells and CD4+T cell subpopulation was enhanced. Pectin intervention in the primary-preventive stetting significantly triggered serum IgA levels, whereas production of IgE and mMCPT-1 was reduced. Remarkably, in both settings peach allergen-specific IgG1/IgG2a ratio and specific IgE were significantly reduced to baseline. The data suggest, that dietary supplementation of pectin in both intervention approaches can diminish inflammatory responses and signs of allergic immune responses, accompanied by alteration of the gut microbiota composition.

Effects of supplemental feeding of Chinese herbal mixtures to perinatal sows on reproductive performance, immunity, and breast milk quality of sows.

The aim of this study was to investigate the impact of supplementary feeding with Chinese herbal mixtures on perinatal sows, focusing on their reproductive performance, immunity and breast milk quality. Sixty healthy pregnant sows (Large white, 4 parities) were randomly allocated into five treatment groups (n = 12 per group): the control group received a basal diet, the TRT1 group received a basal diet supplemented with 2 kg/t Bazhen powder (BZP), while the TRT2, TRT3, and TRT4 groups received a basal diet supplemented with 1 kg/t, 2 kg/t, and 3 kg/t Qi-Zhu-Gui-Shao soothing liver and replenishing blood powder (QZGSP), respectively. The trial lasted for a duration of 5 weeks, commencing from day 100 of gestation and concluding on day 21 postpartum. The results showed that supplemental feeding of 2 kg/t and 3 kg/t QZGSP to periparturient sows significantly improved reproductive performance to different degrees, as evidenced by the shortened farrowing intervals and increased average daily feed intake and milk yield. Supplemental feeding of 2 kg/t and/or 3 kg/t QZGSP significantly elevated levels of IL-4, IL-10, IgG, and IgA in sow serum while reduced levels of TNF-α and IL-1β in sow serum. In addition, supplemental feeding of 2 kg/t and 3 kg/t QZGSP to perinatal sows significantly increased the protein and fat content in colostrum and milk. Analysis of 16S rRNA gene amplicon sequencing data in colostrum and milk microbiota revealed that supplemental feeding of QZGSP to perinatal sows is influenced the composition of colostrum and milk composition in sows. Specifically, at the genus level, a decrease in the relative abundance of Escherichia-Shigella, Staphylococcus and Streptococcus was observed in the TRT3 and/or TRT4 groups on day 0 of lactation. The findings from this study indicate that supplemental feeding of 2 kg/t and 3 kg/t QZGSP significantly improved the reproductive performance, immunity and milk quality in sows. Therefore, QZGSP is a beneficial feed additive for perinatal sows.

Effect of Music Therapy on Anxiety, Stress and Sedative Requirements in Patients Undergoing Lower Limb Orthopedic Surgery Under Spinal Anesthesia: A Randomized Controlled Study.

Background Music therapy is a safe, non-pharmacological way to help reduce anxiety, especially before surgery. It helps to calm the nervous system, promotes relaxation, and offers comfort by blocking outside noise and distracting from pain. This can be helpful in managing preoperative anxiety and symptoms like hypertension and tachycardia. While the benefits of music therapy for stress and sedation are well known, its specific effects on patients receiving spinal anesthesia haven't been studied yet. Understanding this could improve care for these patients. Overall, music therapy could be a valuable tool in the surgical process. Objectives Primary objective: The study aimed to compare sedative requirements between two patient groups. Secondary objectives: To compare anxiety levels between two patient groupsusing the State-Trait Anxiety Inventory. It also assessed hemodynamic changes and measured stress levels by analyzing serum cortisol and immunoglobulin A levels in both groups. Materials and methods Ninety-two American Society of Anesthesiologists physical status class I and II patients, aged 18-65 years, with a body mass index of 18-25 kg/m2 undergoing lower limb orthopedic surgery under spinal anesthesia were selected for the study. After spinal anesthesia, the group M (n=46)patients received the music of their choice from headphones connected to mobile phones and patients in group NM (n=46)were attached headphones without any music therapy. After the attachment of headphones, propofol was administered in both the groups for sedation in a bolus dose of 1-2mg/kg iv followed by an infusion dose of 5-50 μg/kg/min. The propofol infusion was titrated based on Bispectral Index (BIS) values kept between 70 and 80 for moderate sedation. Preoperatively, blood samples were collected to measure baseline serum cortisol and IgA levels. Intraoperatively, hemodynamic parameters were measured, and anxiety level was assessed using the State-Trait Anxiety Inventory (STAI) Scale 30 minutes prior to the administration of spinal anesthesia. Postoperatively, anxiety was re-evaluated, and additional blood samples for the assessment of cortisol and IgA were taken at 30 minutes and 12 hours after the administration of spinal anesthesia. Results The mean serum cortisol was lower in Group M as compared to Group NM (15.1±1.2 vs. 17.1±1; p = 0.0001). Mean serum IgA was significantly lower in Group M as compared to Group NM (269.3±54.5 vs. 294.2±49.9; p = 0.024) during the intraoperative period. The mean STAI Score was lower in Group Mcompared to Group NM (34.87±4.53 vs. 34.61±5.06; p = 0.008). The mean propofol requirement (mg) was lower in Group M as compared to Group NM (147.8±11.3 vs. 193±16; p = 0.0001). The hemodynamic parameters were comparable between the groups (p>0.05). Conclusion Patients in the music therapy group experienced lower anxiety, stress, and serum cortisol levels during surgery, with reduced serum IgA levels and decreased propofol requirement for sedation. Overall, music therapy was effective in reducing anxiety, stress, and sedative requirements during surgery under regional anesthesia.

Rotavirus-specific-IgA and cytokines responses in Ascaris lumbricoides-infected preschool-aged Nigerian children following rotavirus vaccination

ABSTRACT Rotavirus diarrhea and Ascaris lumbricoides (Al) infection increase intestinal morbidity and were associated with altered immune responses that compromise the vaccine efficacy in children. The serum level of rotavirus specific IgA (RV-IgA) and cytokine profiles in A. lumbricoides (AI) infected preschool-aged Nigerian children were estimated following oral rotavirus vaccination. Nineteen of the 149 preschool-aged children (aged 6 to 60 months) with Ascaris lumbricoides infection paired with age and sex-matched helminth – free children were administered with oral rotavirus vaccine after intestinal helminth screening using stool sample concentration technique. Separated sera from 3 mL venous blood samples were collected and estimated for cytokines (IFN–γ, TNF–α, IL-4, IL-8 IL-6, IL-10) and RV-IgA before and three weeks after rotavirus vaccination using Enzyme Linked Immunosorbent Assay. IFN–γ, IL-8, IL-4 were significantly lower at post-vaccination in Al-infected children compared with pre-vaccination. Serum IL-10 was significantly higher at post-vaccination in both Al-infected children and helminth-free controls, compared with pre-vaccination levels (p < 0.05). Pre-vaccination IL-8 and IL-6 were significantly higher in Ascaris lumbricoides–infected children, while the post-vaccination IL-8 was significantly higher in Ascaris lumbricoides–infected compared with control. At post-vaccination period, RV-IgA level was lower in Al-infected children and significantly higher in helminth – free control group compared to pre-vaccination RV-IgA level. Ascaris lumbricoides infection contributed to down-regulation of some cytokines and antibody responses to oral rotavirus vaccine.

Patients With Immunoglobulin A Nephropathy Show Abnormal Frequencies of B Cell Subsets, Unconventional T Cells, and High Levels of Galactose-Deficient IgA1–Coated Gut Bacteria

BackgroundMucosal inflammation is involved in the pathophysiology of Immunoglobulin-A nephropathy (IgAN), but peripheral immune phenotype analyses of IgAN patients often do not include unconventional T cells, the major subset in mucosal immunity. MethodsWe measured serum total IgA, gd-IgA1, secretory IgA, B cell activating factor (BAFF), and A proliferation-inducing ligand (APRIL) in 66 IgAN patients and 30 healthy controls (HC). We also quantified total IgA and gd-IgA1 in stool supernatant and coated on bacteria. In 35 patients and 14 controls, we performed extensive phenotyping (CyTOF) of circulating immune cells, including unconventional T cells [mucosal associated invariant T (MAIT) cells, γδ T, and NK T cells]. The results were validated using RNAseq data from a larger cohort of 179 patients with IgAN, 140 patients with minimal change disease (MCD), and 91 HC. ResultsIgAN patients had higher circulating levels of total IgA, gd-IgA1, and APRIL and higher IgA- and gd-IgA1-coated gut bacteria than controls, while serum levels of secretory IgA and BAFF did not differ between groups. IgAN patients showed more class switched memory and double negative B cells than controls. MAIT cells and γδ T cells were significantly lower, and CD4- CD8- NK T cells significantly higher in IgAN patients than in HC. We validated the significant decrease in MAIT cells in an independent cohort of patients with IgAN. ConclusionThe data indicate that patients with IgAN have increased circulating class switched memory and double negative B cells associated with abnormal T cell immunity, involving defects in unconventional T cell frequency. This may suggest putative alterations at mucosal sites due to cell migration leading to altered IgA production.

Вплив імуносупресивної терапії на стан імунного захисту в дітей

For the treatment of rheumatological diseases, autoimmune lymphoproliferative syndrome and nephrotic syndrome in children, glucocorticosteroid therapy with/without cytostatics is used. Immunosuppression is a serious side effect of these medications. Aim - to investigate immunological parameters in children receiving immunosuppressive therapy in order to determine vaccination tactics. Materials and methods. 50 healthy children (comparison group) and 34 children who received immunosuppressive therapy for rheumatological pathology, autoimmune lymphoproliferative syndrome or nephrotic syndrome (study group) participated in the study. Patients who received high-dose immunosuppressive therapy (n=16) made up the subgroup I, low-dose immunosuppressive therapy (n=18) - the subgroup II. Determination of subpopulations of blood lymphocytes was carried out by the method of flow cytometry, serum immunoglobulins - by the method of radial immunodiffusion. Statistical analysis was performed using the SPSS 23.0 software package. Results. In children who received immunosuppressive therapy, a significant increase in the number of T-lymphocytes (CD3+), a decrease in B-lymphocytes (CD19+) and NK cells (CD3-CD16/56+) was established, while the average levels of serum IgA, IgM, IgG did not differ from the indicators of healthy children, which demonstrates the preservation of humoral immunity. However, in children who received high-dose immunosuppressive therapy, a dose-dependent decrease in the level of serum IgA, IgM, and IgG was found, respectively, by 1.7, 1.3 times, and by 18.9%. Conclusions. It is advisable to vaccinate children before starting immunosuppressive therapy for rheumatological pathology or nephrotic syndrome. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of all participating institutions. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

Intrathecal IgG and IgM synthesis correlates with neurodegeneration markers and corresponds to meningeal B cell presence in MS

Intrathecal synthesis of immunoglobulins (Igs) is a key hallmark of multiple sclerosis (MS). B cells are known to accumulate in the leptomeninges of MS patients and associate with pathology in the underlying cortex and a more severe disease course. However, the role of locally produced antibodies in MS brain pathology is poorly understood. Here, we quantified the protein levels of IgA, IgM, IgG and albumin in serum and cerebrospinal fluid (CSF) samples of 80 MS patients and 28 neurological controls to calculate Ig indices. In addition, we quantified presence of meningeal IgA+, IgM+ and IgG+ B cells in post-mortem brain tissue of 20 MS patients and 6 controls using immunostainings. IgM and IgG, but not IgA, indices were increased in CSF of MS patients compared to controls, with no observed differences between MS disease types. Both IgM and IgG indices correlated significantly with neurofilament light (NfL) levels in CSF, but not with clinical or radiological parameters of disease. Similarly, IgG+ and IgM+ B cells were increased in MS meninges compared to controls, whereas IgA+ B cells were not. Neuronal loss did not differ between sections with low or high IgA+, IgM+ and IgG+ B cells, but was increased in sections with high numbers of all CD19+ meningeal B cells. Similarly, high presence of CD19+ meningeal B cells and IgG+ meningeal B cells associated with increased microglial density in the underlying cortex. Taken together, intrathecal synthesis of IgG and IgM is elevated in MS, which corresponds to an increased number of IgG+ and IgM+ B cells in MS meninges. The significant correlation between intrathecal IgG and IgM production and NfL levels, and increased microglial activation in cortical areas adjacent to meningeal infiltrates with high levels of IgG+ B cells indicate a role for intrathecal IgM- and IgG-producing B cells in neuroinflammatory and degenerative processes in MS.

Effects of Bacterial Lysates on TLRs/NF-κB Pathway, Immune Function, and Prognosis in Children with Pulmonary Infection Caused by Streptococcus pneumoniae

Background: Bacterial lysates, as immunomodulators, may play a role in regulating the host immune response. Objectives: This study aimed to investigate the effects of bacterial lysates OM85-BV in treating pulmonary infections caused by Streptococcus pneumoniae in children. Methods: A total of 120 children with S. pneumoniae pulmonary infection were divided into two groups: The control group and the OM85-BV group, with a 1: 1 ratio. The control group received intravenous mezlocillin at 100 mL/kg/d, while the OM85-BV group, in addition to mezlocillin, received OM85-BV orally at 3.5 mg per dose. The improvement of clinical symptoms and pulmonary function indexes—including respiratory rate, tidal volume, volume to peak expiratory flow as a proportion of exhaled volume, and time to peak tidal expiratory flow as a proportion of expiratory time—were compared. Additionally, levels of C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), soluble interleukin-2 receptor (sIL-2R), T lymphocyte subsets, and immunoglobulins in serum were analyzed. Results: Compared to the control group, the OM85-BV group showed a significant decrease in respiratory rate and an increase in tidal volume, volume to peak expiratory flow, and time to peak tidal expiratory flow (P &lt; 0.05 for all). The OM85-BV group also had significantly lower levels of serum inflammatory factors such as CRP, TNF-α, IL-6, and sIL-2R. In terms of immune function, the OM85-BV group showed increased levels of T lymphocyte subsets CD3+, CD4+, and CD4+/CD8+ ratios, with a decrease in CD8+, as well as elevated serum IgA and IgG levels. The total effective rate of treatment in the OM85-BV group was significantly higher than in the control group (P &lt; 0.05). Conclusions: The addition of OM85-BV to the treatment of S. pneumoniae pulmonary infection in children significantly improves clinical symptoms, lung function, and immune function, while reducing the inflammatory response. OM85-BV appears to inhibit the activation of the toll-like receptors (TLRs) and nuclear factor kappa-B (NF-κB) pathway.

Combination of Acanthocyturia and Elevated Serum IgA Level for the Diagnosis of IgA Nephropathy

Combination of Acanthocyturia and Elevated Serum IgA Level for the Diagnosis of IgA Nephropathy

A Polysaccharide-Based Oral-Vaccine Delivery System and Adjuvant for the Influenza Virus Vaccine.

Influenza virus enters the host body through the mucosal surface of the respiratory tract. An efficient immune response at the mucosal site can interfere with virus entry and prevent infection. However, formulating oral vaccines and eliciting an effective mucosal immune response including at respiratory mucosa presents numerous challenges including the potential degradation of antigens by acidic gastric fluids and the risk of antigen dilution and dispersion over a large surface area of the gut, resulting in minimal antigen uptake by the immune cells. Additionally, oral mucosal vaccines have to overcome immune tolerance in the gut. To address the above challenges, in the current study, we evaluated inulin acetate (InAc) nanoparticles (NPs) as a vaccine adjuvant and antigen delivery system for oral influenza vaccines. InAc was developed as the first polysaccharide polymer-based TLR4 agonist; when tailored as a nanoparticulate vaccine delivery system, it enhanced antigen delivery to dendritic cells and induced a strong cellular and humoral immune response. This study compared the efficacy of InAc-NPs as a delivery system for oral vaccines with Poly (lactic-co-glycolic acid) (PLGA) NPs, utilizing influenza A nucleoprotein (Inf-A) as an antigen. InAc-NPs effectively protected the encapsulated antigen in both simulated gastric (pH 1.1) and intestinal fluids (pH 6.8). Moreover, InAc-NPs facilitated enhanced antigen delivery to macrophages, compared to PLGA-NPs. Oral vaccination studies in Balb/c mice revealed that InAc-Inf-A NPs significantly boosted the levels of Influenza virus-specific IgG and IgA in serum, as well as total and virus-specific IgA in the intestines and lungs. Furthermore, mice vaccinated with InAc-Inf-A-NPs exhibited notably higher hemagglutination inhibition (HI) titers at mucosal sites compared to those receiving the antigen alone. Overall, our study underscores the efficacy of InAc-NPs in safeguarding vaccine antigens post-oral administration, enhancing antigen delivery to antigen-presenting cells, and eliciting higher virus-neutralizing antibodies at mucosal sites following vaccination.

Botanical Bioflavonoid Composition from Scutellaria baicalensis- and Acacia catechu-Protected Mice against D-Galactose-Induced Immunosenescence, and Cyclophosphamide Induced Immune Suppression.

Oxidative stress and chronic inflammation create a perpetual cycle in the elderly, where impaired immune function amplifies susceptibility to oxidative damage, and oxidative stress further weakens the immune response. This cycle is particularly detrimental to the respiratory system of the elderly, which is an easy target for constant exogenous harmful attacks during cold/flu season or under heavy air pollution. Herbal medicines that protect respiratory function are seen as safer alternatives to conventional therapies; however, there is limited availability of scientifically validated, safe, and effective natural supplements for these conditions. In this study, we evaluated a standardized bioflavonoid composition, UP446, that contains bioactives from the roots of Scutellaria baicalensis and the heartwoods of Acacia catechu as a natural and nutritional supplement for its antioxidative and immunoregulatory effects in oxidative stress-accelerated aging and chemically induced immune suppression mouse models. Immunosenescence was induced through the repeated subcutaneous inoculation of D-galactose (D-Gal) at a dose of 500 mg/kg/day in CD-1 mice. UP446 was administered orally at doses of 100 mg/kg and 200 mg/kg starting in the fifth week of immunosenescence induction. This study lasted a total of ten weeks. All mice received a quadrivalent influenza vaccine 2 weeks before termination. Whole blood, serum, spleen homogenate, and thymus tissues were processed for analysis. Cyclophosphamide (Cy)-induced immunosuppression was triggered by three consecutive injections of cyclophosphamide at 80 mg/kg/day, followed by the oral administration of UP446 for 18 days at doses of 100 mg/kg and 200 mg/kg. Blood was collected from each animal at necropsy, and serum was isolated for IgA and IgG ELISA analysis. UP446 was found to improve immune response, as evidenced by the stimulation of innate (NK cells) and adaptive immune responses (T cells and cytotoxic T cells), an increase in antioxidant capacity (glutathione peroxidase), the preservation of vital immune organs (the thymus), and a reduction in NFκB. UP446 also increased serum levels of IgA and IgG. The findings presented in this report demonstrate the antioxidative, anti-inflammatory, and immune-regulatory activities of UP446, suggesting its potential use in respiratory conditions involving immune stress due to aging, oxidative stress, and/or pathogenic challenges.

Evaluation of lyophilized bacteriophage cocktail efficiency against multidrug-resistant Salmonella in broiler chickens

Currently, phage biocontrol is increasingly used as a green and natural technology for treating Salmonella and other infections, but phages exhibit instability and activity loss during storage. Therefore, in this study, the effects of lyophilization on the activity and stability of phage cocktails for the control of multidrug-resistant Salmonella in broiler chickens were determined. Eight serotypes of Salmonella were isolated and identified from broiler chicken farms, and bacteriophages against multidrug-resistant Salmonella enterica subsp. enterica serovar Kentucky, Salmonella enterica subsp. enterica serovar Typhimrium and Salmonella enterica subsp. enterica serovar Enteritidis were isolated. The bacteriophage cocktail was prepared and lyophilized, and it was subjected to in vitro and in vivo examinations. A reconstituted lyophilized bacteriophage cocktail was used for the oral treatment of chicks before and after challenge with multidrug-resistant S. Kentucky. The colonization of cecum by S. Kentucky was detected by using real-time PCR, and the serum levels of IgM, IgA and IL-4 and pathological changes in the different groups were detected. Three Caudovirales phages families were identified including Autographiviridae, Straboviridae and Drexlerviridae against multidrug-resistant S. Kentucky, S. Typhimrium and S. Enteritidis. The groups treated with the bacteriophage cocktail showed no clinical signs, no postmortem lesions, and a mortality rate of 0%, which improved the growth performance parameters. Additionally, the estimated serum levels of IgM, IgA and IL-4 were significantly greater in the bacteriophage cocktail-treated groups. Lyophilization effectively preserves the long-term storage stability of phages. Therefore, lyophilized bacteriophage cocktail therapy is a valuable approach for controlling multidrug-resistant Salmonella infections in broiler chickens.