Serum IgA Levels Research Articles

Avian safety guardian: Luteolin restores Mycoplasma gallisepticum-induced immunocompromise to improve production performance via inhibiting the IL-17/NF-kB pathway

Mycoplasma gallisepticum (MG) is a major pathogen causing chronic respiratory disease (CRD) in chickens. Exposure to MG poses a constant threat to chicken health and causes substantial economic losses. Antibiotics are the main treatment for MG infections, but have to struggle with antibiotic residues and MG resistance. To date, no safe and more effective prevention or treatment for MG infections has been identified. Luteolin (Lut) is a natural flavonoid compound known for its excellent anti-viral, anti-bacterial, immunoregulatory, and anti-inflammatory pharmacological activities. Herein, we established an MG-infected model using partridge shank chickens and chicken-like macrophages (HD11 cells) to investigate the effect and potential mechanism of Lut against MG-induced immune damage.According to our findings, Lut significantly inhibited the expression of MG adhesion protein (pMGA1.2) in vivo and in vitro. Lut effectively mitigated the MG-induced decrease in body weight gain, feed conversion ratio, survival rate, and serum IgG and IgA levels. Lut directly repaired MG-induced spleen and thymus damage by histopathological analysis. Furthermore, network pharmacology analysis revealed that Lut most probably resisted MG infection through the IL-17/NF-kB pathway. In vivo and in vitro experiments, Lut significantly suppressed the increase in key protein IL-17A, TRAF6, p-p65, and p-IkBα in the IL-17/NF-kB pathway. Meanwhile, Lut markedly alleviated MG-induced the increase of pro-inflammatory cytokines TNF-α, IL-6, IL-1β, pro-apoptotic genes caspase3 and caspase9, while promoting the expression of anti-apoptotic genes Bcl-2 and Bcl-XL.In summary, Lut effectively suppressed MG colonization, alleviated MG-induced the production performance degradation, inflammatory responses, and immune damage by inhibiting the IL-17/ NF-kB pathway. This study indicates Lut can serve as a safe and effective antibiotic alternative drug for preventing and treating MG-induced CRD. It also provides new evidence to explore the molecular mechanisms of MG infection.

Effects of dustbathing environment on gut microbiota and expression of intestinal barrier and immune-related genes of adult laying hens housed individually in modified traditional cage

Litters, the composition of sand and peat rich in microbiota, are essential to trigger the dustbathing behavior of chickens. To investigate the effects of a dustbathing environment (DE) on the intestinal health, gut microbiota, and immune responses of laying hens, a total of 72 healthy Hy-Line Brown laying hens at 69 wk of age (WOA) were housed individually in modified traditional cages and randomly divided into 2 groups: one group had free access to litters (CT), while the other one was restricted from litters (CC). The experiment lasted for 42 d. At the end of the experiment, the intestinal histomorphology and immune status of laying hens were determined, and the 16S rRNA sequencing method was used to assess the composition of the intestinal microbial community of birds. Intestinal histomorphology changed, including villus height and villus-to-crypt ratio significantly increased in the CT group (P < 0.01). DE reshaped the microbial community and increased the microbial richness with the higher indicators of Chao1 and observed species and the comparatively abundant beta diversity (P < 0.05). Ten genera, including Faecalibacterium and Coprococcus, declined in laying hens from the CT group (P < 0.05), while Alistipes increased in CT hens (P < 0.05) compared to those hens from the CC group. The expression levels of intestinal barrier-related genes of claudin-1, claudin-4, occludin, ZO-1, and ZO-2 and immune-related genes of IL-4, IL-6, IL-8, IFN-γ, IgA, TLR-2, and TLR-4 were significantly upregulated in the intestine of laying hens in CT group (P < 0.05). DE also increased the serum levels of IL-4, IL-6, IL-8, IFN-γ, and IgA (P < 0.01). The alteration of the gut microbiota by DE is closely related to host immune responses, including Lactobacillus positively correlated with IL-4 and IgA. Thus, a dustbathing environment can improve the welfare of laying hens by changing the intestinal histomorphology, immune response, and the gut microbial community.

Dietary Macleaya cordata extract supplementation improves the growth performance and gut health of broiler chickens with necrotic enteritis

BackgroundThe poultry industry needs effective antibiotic alternatives to control outbreaks of necrotic enteritis (NE) caused by Clostridium perfringens.MethodsThe aim of this study was to investigate the effects of dietary supplementation with Macleaya cordata extract (MCE) on the immune function and gut microbiota of broilers with NE. A total of 288 1-day-old broiler chicks were randomly assigned to a 2 × 2 factorial arrangement with two concentrations of dietary MCE supplementation (0 or 350 mg/kg of diet) and two disease challenge statuses (control or NE).ResultsThe results revealed that NE significantly increased the feed conversion rate (FCR), mortality, intestinal lesion score, the levels of IL-1β, IL-17 and IFN-γ/IL-4 in serum and IL-17/IL-10 in the jejunal mucosa, mRNA levels of TLR2, IFN-γ and pIgR in the jejunum, and Clostridium perfringens concentrations in the cecum. NE significantly decreased the body weight (BW), body weight gain (BWG), jejunal villus height, V/C, mRNA level of AMPK-α1 in jejunum, IL-4 level in the jejunal mucosa and lactic acid bacteria abundance in the cecum. MCE significantly increased BW, BWG, jejunal villus height, V/C, mRNA levels of occludin, ZO-1 and AMPK-α1 in the jejunum, the levels of IgA and IgG in serum and IL-10 in the jejunal mucosa and mRNA levels of NF-κB, IL-10 and MHC-II in the jejunum. Additionally, MCE significantly decreased the FCR, mortality, intestinal lesion score, jejunal crypt depth, the levels of IFN-γ and IL-17 in serum and IL-17/IL-10 in the jejunal mucosa, Clostridium perfringens concentrations in the cecum, and mRNA levels of IL-17/IL-10 in the jejunum. Moreover, NE significantly increased the abundance of bacteria that are associated with inflammation, obesity and depression (Alistipes, Barnesiella, Intestinimonas, RF39 and UCG-005) and significantly decreased the abundance of short-chain fatty acid (SCFA)-producing bacteria (Anaerotruncus, Butyricicoccus and Bacteroides) in the cecum. MCE significantly increased the abundance of SCFA-producing bacteria (Streptococcus, Ruminococcus_torques_group and Lachnospiraceae_NK4A136_group) and significantly reduced the abundance of bacteria that are associated with inflammation and obesity (Alistipes, Barnesiella and UCG-010) in the cecum. In the cecum of broilers with NE, the relative abundance of Barnesiella and Alistipes was higher and that of Lachnoclostridium and Shuttleworthia was lower. Interestingly, these trends were reversed by the addition of MCE to the diet. Spearman correlation analysis showed that Barnesiella and Alistipes were associated with enhanced intestinal inflammation and inhibited growth performance, whereas Lachnoclostridium and Shuttleworthia were associated with anti-inflammatory effects.ConclusionsMCE ameliorated the loss of growth performance in broiler chickens with NE, probably by regulating the intestinal barrier, immune function, and gut microbiota.

Supplementation with Rumen-Protected Methionine Reduced the Parasitic Effect of Haemonchus contortus in Goats.

The present study investigated the impact of rumen-protected (RP) methionine supplementation on the resistance and resilience to Haemonchus contortus experimental infection of goat kids. Twenty-seven 6-month-old goat kids (14.55 ± 2.7 kg body weight) were placed in individual pens during an experimental period of forty-two days. Each kid was placed under one of three distinct diets (n = 9 animals/diet) corresponding to the following experimental groups: Control (C, Hay + concentrate), Low Methionine (LM, Hay + concentrate + 3.5 g/Kg of Dry Matter (DM) of RP methionine, or High Methionine (HM, Hay + concentrate + 11.5 g/Kg of DM of RP methionine). After a 4-week period of adaptation to the diets, all the animals were experimentally infected with a single oral dose of 10,000 H. contortus third-stage infective larvae (L3). No significant effect of RP methionine supplementation was observed for feed intake, digestibility and growth performance. The faecal egg counts (FEC) and worm burdens were not impacted by RP methionine supplementation either. In contrast, Packed cell volume (PCV) and haemoglobin concentration were higher in kids supplemented with RP methionine. Similarly, the level of serum IgA directed against adult H. contortus excretion and secretion products (ESP) was higher in supplemented kids. These results suggested that RP methionine supplementation improved goat kids' resilience against H. contortus infection.

Effects of two strains of Lactobacillus isolated from the feces of calves after fecal microbiota transplantation on growth performance, immune capacity, and intestinal barrier function of weaned calves.

Weaning stress seriously affects the welfare of calves and causes huge economic losses to the cattle breeding industry. Probiotics play an important role in improving animal growth performance, enhancing immune function, and improving gut microbiota. The newly isolated strains of Lactobacillus reuteri L81 and Lactobacillus johnsonii L29 have shown potential as probiotics. Here, we studied the probiotic properties of these two strains on weaned calves. Forty calves were randomly assigned to four groups before weaning, with 10 calves in each group, control group (Ctrl group), L. reuteri L81 supplementation group (2 g per day per calf), L. johnsonii L29 supplementation group (2 g per day per calf), L. reuteri L81 and L. johnsonii L29 composite group (2 g per day per calf), and the effects of Lactobacillus reuteri L81 and Lactobacillus johnsonii L29 supplementation on growth performance, immune status, antioxidant capacity, and intestinal barrier function of weaned calves were evaluated. The results showed that probiotics supplementation increased the average daily weight gain of calves after weaning, reduced weaning diarrhea index (p < 0.05), and increased serum IgA, IgM, and IgG levels (p < 0.05). L. reuteri L81 supplementation significantly decreased IL-6, increased IL-10 and superoxide dismutase (SOD) levels at 21 d after weaning (p < 0.05). Moreover, probiotics supplementation significantly decreased serum endotoxin (ET), diamine oxidase (DAO), and D-lactic acid (D-LA) levels at different time points (p < 0.05). In addition, supplementation with L. reuteri L81 significantly reduced the crypt depth and increased the ratio of villus height to crypt depth (p < 0.05) in the ileum, increased gene expression of tight junction protein ZO-1, Claudin-1 and Occludin in jejunum and ileum mucosa, reduced the gene expression of INF- γ in ileum mucosa and IL-8 in jejunum mucosa, and increased the abundance of beneficial bacteria, including Bifidobacterium, Lactobacillus, Oscillospira, etc. verall, these results showed that the two strains isolated from cattle feces after low concentration fecal microbiota transplantation improved the growth performance, immune performance, antioxidant capacity, and intestinal barrier function of weaned calves, indicating their potential as supplements to alleviate weaning diarrhea in calves.

Yishen Juanbi Decoction Combined with Predictive Nursing Intervention Improves the Prognosis, Pain, and Nutritional Status of Patients with Ankylosing Spondylitis

We have examined the effect of Yishen Juanbi decoction combined with predictive nursing intervention on the prognosis, pain, and nutritional status of patients with ankylosing spondylitis. Ankylosing spondylitis patients received oral Yishen Juanbi decoction, followed by routine nursing intervention or predictive nursing intervention. The visual analog scale score and bath ankylosing spondylitis functional index score in the predictive nursing intervention were lower relative to the routine nursing intervention (P &lt; 0.05). The predictive nursing intervention also had better quality of life than the routine nursing intervention group (P &lt; 0.05). Serum total protein and albumin levels were higher in the predictive nursing intervention group than the routine nursing intervention group (P &lt; 0.05), while serum IgA, IgM, and IgG levels were lower (P &lt; 0.05). The nursing satisfaction of patients in the predictive nursing intervention group was higher compared to the routine nursing intervention group (P &lt; 0.05). In conclusion, Yishen Juanbi decoction combined with predictive nursing can reduce pain, improve the nutritional status, and promote the motor function and quality of life of ankylosing spondylitis patients.

Salivary antibodies induced by BA.4/BA.5-convalescence or bivalent booster Immunoglobulin vaccination protect against novel SARS-COV-2 variants of concern.

Currently, SARS-CoV-2 Omicron BA.5 subvariants BF.7 and BQ.1.1 are rapidly emerging worldwide. To evaluate the SARS-CoV-2-neutralizing capacity of sera and saliva from triple vaccinated individuals, either boosted with an adapted bivalent COVID-19 vaccine or recovered from BA.4/BA.5 infection, we analyzed the sensitivity of replication-competent SARS-CoV-2 Omicron subvariants BA.4/5, BQ.1.1 and BF.7 to neutralization. Analysis of SARS-CoV-2-specific IgGs and IgAs showed increased serum IgG titers in the vaccinated group, while the serum and salivary IgA levels were comparable. Similar and efficient serum neutralization against the ancestral strain of SARS-CoV-2 and Omicron BA.4/BA.5 was detected in both cohorts, but critically reduced for BQ.1.1 and BF.7. In contrast, salivary neutralization against BA.4/BA.5 was increased in the convalescent compared to the vaccinated group, while salivary neutralizing capacity against BQ.1.1 and BF.7 was comparable in these groups. Further, personalized protective effects studied in a human 3D respiratory model revealed the importance of salivary protection against different Omicron subvariants. IMPORTANCE In BA.4/BA.5-convalescent versus vaccinated groups, salivary neutralization capacity increased against SARS-CoV-2 Omicron BA.4/BA.5. In contrast, it neutralized novel Omicron subvariants BQ.1.1 and BF.7 similarly. Salivary protection against various Omicron subvariants was even more evident when tested in a personalized approach using highly differentiated respiratory human 3D models.

Umbilical Cord Blood IgA Levels and Bacterial Profile in Preterm Neonates Born with Maternal Risk Factors for Early-Onset Neonatal Sepsis.

To investigate the IgA levels and bacterial profile in umbilical cord blood (UCB) samples of mothers with risk factors compared to those without risk factors; and to understand the link between UCB culture positivity and neonatal outcomes [early-onset sepsis (EOS) or death within 7 d of life]. This is a pilot prospective case-control study. Mothers with preterm deliveries (gestational age <34 wk) were enrolled in two groups- Cases: Those with antenatal risk factors (prolonged duration of rupture of membranes of ≥24h or chorioamnionitis) and controls: Those without these two risk factors. Serum IgA levels was assayed and microbiological culture was tested in UCB samples. 16S sequencing to determine the UCB microbiome was performed in a subset of samples (n = 15). Neonates were followed-up for the occurrence of EOS or death until 7 d of life. Forty-nine mothers as cases and 50 mothers as controls were consecutively enrolled. No significant difference was observed in the IgA levels (60.5 vs. 58.1mg/L; p = 0.71), neonatal blood culture positivity (4.1% vs. 8.0%; p = 0.41) and UCB culture positivity (30.6% vs. 26.0%; p = 0.61) in the two groups.No difference was observed between the groups in occurrence of EOS or death within 7 d of life. Proteobacteria, Firmicutes and Actinobacteria were the most abundant phyla. Serratia, Bifidobacterium, Collinsella, Meganomas and Blautia being the most common genera. Cord blood IgA concentration could not differentiate the neonates at-risk of infection due to its presence in both the groups.

Evaluation of the immunoprotective effects of eight recombinant proteins from Baylisascaris schroederi in mice model

BackgroundBaylisascaris schroederi is the most common and harmful intestinal parasitic nematode of giant pandas, causing ascariasis. Although drug deworming is the main measure to control ascariasis in captive giant pandas, prolonged and repeated use of deworming drugs might induce resistance in nematodes and drug residues in giant pandas. Therefore, developing a safe and effective vaccine might provide a novel strategy to prevent ascariasis in captive giant pandas.MethodsFour highly expressed secretome genes encoding excretory and secretory proteins of B. schroederi, including transthyretin-like protein 46 (BsTLP), uncharacterized protein (BsUP), hypothetical protein 1 (BsHP1), and hypothetical protein 2 (BsHP2) and four functional genes [(encoding Galectin (BsGAL), glutathione S-transferase (BsGST), fatty acid-binding protein (BsFABP), and thioredoxin peroxidase (BsTPX)] were identified based on genome and transcriptome databases of B. schroederi and used to construct recombinant proteins via prokaryotic expression. Kunming mice were vaccinated subcutaneously twice with the recombinant proteins (50 μg/mouse) mixed with Quil A adjuvant with a 2-week interval and then orally challenged with 3000 infective eggs. The immunoprotective effects of the eight recombinant proteins on mice were assessed comprehensively using surface lesion histology scores of the mouse liver and lung, larval worm reduction, serum antibody levels (IgG, IgE, IgA, IgG1, and IgG2a), and cytokine production [interferon gamma (IFN-γ), interleukin (IL)-2, IL-4, IL-5, and IL-10].ResultsMice vaccinated with recombinant (r)BsUP (76.5%), rBsGAL (74.7%), and rBsHP2 (71.5%) showed a significant (P < 0.001) reduction in the larval worm rate compared with that in the adjuvant control. Besides, the surface lesions in the liver and lung of the vaccinated mice were alleviated. Serum levels of total IgG, IgE, IgA, IgG1, IgG2a, and cytokines, including IL-10, IL-5, and IFN-γ, were significantly higher (P < 0.001) than those in the control group.ConclusionsThe results showed that candidate three vaccines (rBsUP, rBsGAL, and rBsHP2) could provide effective protection against egg infection in mice associated with a mixed Th1/2-type immune response.Graphical

Effect of Immune Plasma Therapy on Mortality and Morbidity in Patients with Covid-19: A Retrospective Study

Objective: Immune plasma therapy, a method employed for passive immunization, has been utilized as a treatment modality based on historical precedents during the Covid-19 pandemic, a global crisis resulting in the unfortunate demise of countless individuals. The objective of this study is to investigate the impact of immune plasma therapy on laboratory parameters and the overall survival rate in patients with Covid-19 pneumonia. Material and Methods: Our study was designed as a retrospective analysis, conducted at a tertiary healthcare institution from April 1, 2020, to December 31, 2020. The study population comprised individuals aged 18 and above, presenting with pulmonary involvement, and diagnosed with Covid-19 using the polymerase chain reaction (PCR) method at our hospital. The inclusion criteria encompassed patients who received immune plasma therapy, as well as a control group matched for age, gender, and admission date, who did not undergo immune plasma therapy. Exclusion criteria involved patients with low serum IgA levels, those who did not provide consent for immune plasma therapy, and individuals below the age of 18. Results: The study comprised a total of 72 patients who received immune plasma therapy and 72 patients in the control group, matched for age and gender, all diagnosed with Covid-19. The median age of the patients was 70 years, ranging from 19 to 91, and 56.9% (41) of them were female. When comparing the immune plasma group with the control group, several significant differences were observed (p&lt;0.05). These included elevated levels of leukocytes, neutrophils, neutrophil-lymphocyte ratio (NLR), glucose, aspartate aminotransferase (AST), sedimentation rate, C-reactive protein (CRP), ferritin, fibrinogen, d-dimer, and low levels of platelets and lymphocytes in the control group. Furthermore, in the immune plasma therapy group, significant associations were found between mortality and lymphocyte count, NLR, AST, CRP, and d-dimer elevation after treatment (p&lt;0.05). Additionally, pre- and post-treatment measurements of troponin, procalcitonin, and ferritin were significantly correlated with mortality (p&lt;0.05). Conclusion: The administration of immune plasma therapy, involving the transfer of neutralizing antibodies, has demonstrated a favorable impact on laboratory parameters and overall survival in severe cases of Covid-19 pneumonia, particularly during the early stages of the disease.

Effect of hematuria on the kidney disease progression in IgA nephropathy patients with mild proteinuria and well-preserved renal function

ObjectiveTo investigate whether hematuria is a risk factor in IgA nephropathy (IgAN) patients with mild proteinuria and well-preserved renal function. MethodsThis retrospective study included a total of 63 IgAN patients, with complete clinical data available for 50 patients. Hematuria assessment was conducted using two methods: 1) an automated method using a urine particle analyzer, and 2) a manual method performed by a skilled examiner to examine microscopic urine sediment. ResultsThe results of hematuria measurement using both automated and manual methods showed a strong linear correlation (r = 0.78, P < 0.001). In IgAN patients, those with high urinary red blood cell count (U-RBCs) exhibited higher serum IgA levels compared to patients with low U-RBCs. Additionally, patients with crescent formation had higher levels of proteinuria compared to those without crescents. Patients who received immunosuppressive treatment displayed higher levels of systolic blood pressure (SBP) and mean arterial pressure (MAP), as well as lower levels of serum hemoglobin and albumin. They also had a higher prevalence of T1 lesions compared to patients who did not undergo immunosuppression. Furthermore, among patients with crescent formation, those who received immunosuppressive agents exhibited higher levels of SBP, diastolic blood pressure (DBP), MAP, and U-RBCs, as well as lower levels of albumin and proteinuria at the time of renal biopsy. No composite kidney endpoint events were observed in these groups of patients. The U-RBCs level was not identified as a risk factor influencing the decline of estimated glomerular filtration rate (eGFR) in IgAN. ConclusionsThe presence of hematuria at the time of biopsy was not found to be associated with kidney disease progression in IgAN patients who had mild proteinuria and well-preserved renal function. This suggests that it is possible that these patients may not derive significant benefits from immunosuppressive therapy.

Unveiling a New Perspective on Distinguishing Omicron Breakthrough Cases and Postimmune COVID-19-Naive Individuals: Insights from Antibody Profiles.

In the situation of mass vaccination against COVID-19, few studies have reported on the early kinetics of specific antibodies (IgG/IgM/IgA) of vaccine breakthrough cases. There is still a lack of epidemiological evidence about the value of serological indicators in the auxiliary diagnosis of COVID-19 infection, especially when the nucleic acid results were undetectable. Omicron breakthrough cases post-inactivated vaccination (n = 456) and COVID-19-naive individuals with two doses of inactivated vaccination (n = 693) were enrolled. Blood samples were collected and tested for SARS-CoV-2 antibody levels based on the magnetic chemiluminescence enzyme immunoassay. Among Omicron breakthrough cases, the serum IgG antibody level was 36.34 Sample/CutOff (S/CO) (95% confidence interval [CI], 31.89 to 40.79) in the acute phase and 88.45 S/CO (95% CI, 82.79 to 94.12) in the recovery phase. Serum IgA can be detected in the first week post-symptom onset (PSO) and showed an almost linear increase within 5 weeks PSO. Compared with those of breakthrough cases, IgG and IgA titers of the postimmune group were much lower (4.70 S/CO and 0.46 S/CO, respectively). Multivariate regression showed that serum IgG and IgA levels in Omicron breakthrough cases were mainly affected by the weeks PSO (P < 0.001). Receiver operating characteristic ROC0 curve analysis showed that the area under the curve (AUC) was 0.744 and 0.806 when the cutoff values of IgA and IgG were 1 S/CO and 15 S/CO, respectively. Omicron breakthrough infection can lead to a further increase in IgG and IgA levels relative to those of the immunized population. When nucleic acid real-time PCR was negative, we would use the kinetics of IgG and IgA levels to distinguish the breakthrough cases from the immunized population. IMPORTANCE This study fills a gap in the epidemiological evidence by investigating the value of serological indicators, particularly IgG and IgA levels, in the auxiliary diagnosis of COVID-19 infections when nucleic acid results are undetectable. The findings reveal that among Omicron breakthrough cases, both IgG and IgA antibody levels exhibit significant changes. Serum IgG levels increase during the acute phase and rise further in the recovery phase. Serum IgA can be detected as early as the first week post-symptom onset (PSO), showing a consistent linear increase within 5 weeks PSO. Furthermore, receiver operating characteristic (ROC) curve analysis demonstrates the potential of IgG and IgA cutoff values as diagnostic markers. The study's conclusion underscores the importance of monitoring IgG and IgA kinetics in distinguishing Omicron breakthrough cases from vaccinated individuals. These findings contribute to the development of more accurate diagnostic approaches and help inform public health strategies during the ongoing COVID-19 pandemic.

Limosilactobacillus reuteri DSM 17938 supplementation and SARS-CoV-2 specific antibody response in healthy adults: a randomized, triple-blinded, placebo-controlled trial

ABSTRACT Studies have shown that probiotics can decrease the symptoms of respiratory tract infections as well as increase antibody responses following certain vaccinations. We examined the effect of probiotic supplementation on anti-SARS-CoV-2 specific antibody responses upon SARS-CoV-2 infection as well as after COVID-19 vaccination. In this randomized, triple-blinded, placebo-controlled intervention study with a parallel design, 159 healthy adults without prior SARS-CoV-2 infection or COVID-19 vaccination and any known risk factors for severe COVID-19 were randomly allocated into two study arms. The active treatment arm consumed a probiotic product containing a minimum of 1 × 108 colony-forming units of Limosilactobacillus reuteri DSM 17938 + 10 μg vitamin D3 twice daily for 6 months. The placebo arm consumed identical tablets containing only 10 μg vitamin D3. Anti-SARS-CoV-2 specific antibodies and virus neutralizing antibody titers were analyzed from blood samples collected at baseline, after 3 months, and after 6 months. Differences in serum antibody titers between the two study arms were tested with independent t-test using log-transformed values. In the intention-to-treat (ITT) analysis, SARS-CoV-2 infected individuals in the active treatment arm (n = 6) tended to have higher serum anti-spike IgG (609 [168–1480] BAU/ml vs 111 [36.1–1210] BAU/ml, p = 0.080) and anti-receptor binding domain (RBD) IgG (928 [212–3449] BAU/ml vs (83.7 [22.8–2094] BAU/ml, p = 0.066) levels than individuals in the placebo arm (n = 6). Considering individuals who were fully vaccinated with mRNA-based COVID-19 vaccines, the active treatment arm (n = 10) exhibited significantly higher serum levels of anti-RBD IgA (135 [32.9–976] BAU/ml vs 61.3 [26.7–97.1] BAU/ml, p = 0.036) than the placebo arm (n = 7) >28 days postvaccination. Supplementation with specific probiotics might improve the long-term efficacy of mRNA-based COVID-19 vaccines via enhanced IgA response.

MTMR3 risk alleles enhance Toll Like Receptor 9-induced IgA immunity in IgA nephropathy

Multiple genome-wide association studies (GWASs) have reproducibly identified the MTMR3/HORMAD2/LIF/OSM locus to be associated with IgA nephropathy (IgAN). However, the causal variant(s), implicated gene(s), and altered mechanisms remain poorly understood. Here, we performed fine-mapping analyses based on GWAS datasets encompassing 2762 IgAN cases and 5803 control individuals, and identified rs4823074 as the candidate causal variant that intersects the MTMR3 promoter in B-lymphoblastoid cells. Mendelian randomization studies suggested the risk allele may modulate disease susceptibility by affecting serum IgA levels through increased MTMR3 expression. Consistently, elevated MTMR3 expression in peripheral blood mononuclear cells was observed in patients with IgAN. Further mechanistic studies invitro demonstrated that MTMR3 increased IgA production dependent upon its phosphatidylinositol 3-phosphate binding domain. Moreover, our study provided the invivo functional evidence that Mtmr3-/- mice exhibited defective Toll Like Receptor 9-induced IgA production, glomerular IgA deposition, as well as mesangial cell proliferation. RNA-seq and pathway analyses showed that MTMR3 deficiency resulted in an impaired intestinal immune network for IgA production. Thus, our results support the role of MTMR3 in IgAN pathogenesis by enhancing Toll Like Receptor 9-induced IgA immunity.

Protective Effects of Bacillus subtilis HH2 against Oral Enterotoxigenic Escherichia coli in Beagles.

This study evaluated the protective effect of Bacillus subtilis HH2 on beagles orally challenged with enterotoxigenic Escherichia coli (ETEC). We assessed the physiological parameters and the severity of diarrhea, as well as the changes in three serum immunoglobulins (IgG, IgA, and IgM), plasma diamine oxidase (DAO), D-lactate (D-LA), and the fecal microbiome. Feeding B. subtilis HH2 significantly reduced the severity of diarrhea after the ETEC challenge (p < 0.05) and increased serum levels of IgG, IgA, and IgM (p < 0.01). B. subtilis HH2 administration also reduced serum levels of DAO at 48 h after the ETEC challenge (p < 0.05), but no significant changes were observed in D-LA (p > 0.05). Oral ETEC challenge significantly reduced the richness and diversity of gut microbiota in beagles not pre-fed with B. subtilis HH2 (p < 0.05), while B. subtilis HH2 feeding and oral ETEC challenge significantly altered the gut microbiota structure of beagles (p < 0.01). Moreover, 14 days of B. subtilis HH2 feeding reduced the relative abundance of Deinococcus-Thermus in feces. This study reveals that B. subtilis HH2 alleviates diarrhea caused by ETEC, enhances non-specific immunity, reduces ETEC-induced damage to the intestinal mucosa, and regulates gut microbiota composition.

Allergic Rhinitis and Other Allergic and Autoimmune Disorders in Children with IgA Deficiency

Background: Selective IgA imunodeficiency is the most frequently occurring primary antibody deficiency. Serum IgA level is decreased or even completly absened, while IgM and IgG antibodies displey normal serum levels. IgA plays an important role in immune protection in the gastrointestinal and respiratory tract. Patients with selective IgA imunodeficiency can be asimptomatic (&gt;50% of cases) and can suffer from recurrent gastointestinal and respiratory infecitions, allergies and autoimmune diseases. Allergic rhinitis (AR) is the most common cause of chronic rhinitis. Characteristic feature of allergic rhinitis is eosinophilic inflammation of the nasal mucosa. Several studied have shown that IgA represents a potent trigger of eosinophil degranulation, while other studies have shown that IgA imunodeficiency is a well-known risk factor for atopy. Objective: Objective of this study was to evaluate the frequency of allergic rhinitis and other allergic and autoimmune disorders in children with IgA immunodeficiency. Methods: The study included 36 children diagnosed with IgA imunodeficiency. The presence of allergic and autoimmune disorders was evaluated by specialist of allergology, immunology, rheumatology and otorhinolaryngology. Results: 22 (71,1%) of children were male and the mean age of the patients was 10.5 years. Among the patients 31 (86,11%) had at least one allergic disease: 20 (55,55%) had asthma, 17 (47,22%) had allergic rhinitis, 6 (16,67%) had atopic dermatitis and 5 (13,89%) had urticaria. 14 (38,89%) had at least one of autoimmune disordes: 8 (22,22%) had reactive arthritis, 5 (13,89%) had juvenile idiopathic arthritis, 2 (5,56%) had Mb Hashimoto and 1 (2,78%) had SLE. Conclusion: This study showed that the main clinical manifestations in patients with IgA deficiency were asthma and allergic rhinitis. Results also show increased frequencies in other allergic and autoimmune diseases, compared to available data from general population.

A Case Report of Hyper-IgM Syndrome Patient with Normal Serum IgA Level

Hyper IgM syndromes are a group of disorders characterized by defective T and B cell interactions resulting in the lack of Immunoglobulin class switching. The most common hyper IgM syndrome is CD40 ligand (CD40L) deficiency. Patients with CD40L deficiency present with recurrent infection, neutropenia, and autoimmunity. These patients typically have absent serum IgA and IgG due to the class switch defect. Here we present a case of CD40L deficiency who presented with oral ulcers, failure to thrive, and recurrent fever. His laboratory evaluation was notable for intermittent neutropenia, elevated IgM (397mg/dl), normal IgA (78mg/dl) and low IgG (51mg/dl). Antibody responses to tetanus and measles were undetectable despite full vaccination. Whole exome sequencing showed a likely pathologic variant in CD40LG (c.674 T&gt;C, p.L225S). This case highlights the importance of considering the diagnosis of hyper IgM syndrome in the appropriate clinical setting, even if the patient has a normal serum IgA level.

Effect of Probiotic Therapy on the Vagina Microbiota and the Humoral Link of Immunity in Bacterial Vaginosis

The aim of the research is to determine the effect of the probiotic preparation «Dialak» (dietary supplement), which includes the strain Lactobacillus casei IMV B-7280, on the vaginal microbiota and humoral immunity in women with bacterial vaginosis (BV). Methods. 40 female patients aged 20—45 years with disturbed vaginal microbiota and 10 healthy individuals were examined. The verification of 3 types of vaginal biocenosis states, namely normocenosis, intermediate type, and vaginal dysbiosis, was carried out on the basis of the Recommendations for the Treatment of Sexually Transmitted Infections Weekly Morbidity and Mortality Report (2021) and laboratory diagnostic methods according to the well-known criteria proposed by R. Amsel. Female patients with an intermediate type of BV (group 1) received suppositories and capsules of the probiotic (once daily) for 10 days. Women with vaginal dysbiosis (group 2) received metronidazole in a dosage of 500 mg twice a day for 7 days during the first stage, and then 1 suppository at night and oral capsules of the probiotic in the morning for 10 days during the second stage. The studied vaginal secretion was stained by the Gram method in the Kopeloff modification and also sown on nutrient media to determine facultatively anaerobic and obligately anaerobic microorganisms. Microorganism identification was carried out on the basis of morphological, cultural, biochemical, and antigenic properties according to the classification of D. H. Bergey (2009). The activity of humoral immunity was determined by evaluating the number of B-lymphocytes in the peripheral blood of patients using flow cytometry, as well as the levels of serum Ig A, M, and G before treatment and aft er 1 month using the immunoturbidimetric method and the Cobas 6000 test system from Roche Diagnostics (Switzerland). Results. When analyzing the vaginal microbiota in two groups of patients before treatment, a decrease in the number of Lactobacillus spp. and Bifidobacterium spp. and a significant increase in the number of obligate anaerobic microorganisms, including Gardnerella vaginalis, were found compared to the control group. Before treatment, the number of Lactobacillus spp. in women of group 2 was lower compared to group 1. In patients with vaginal dysbiosis before treatment, the number of obligate anaerobic microorganisms was higher than in patients with bacterial vaginosis, except for Eubacterium spp. At the same time, in women in both comparison groups, the indicators of the humoral immune response were partially disrupted, as evidenced by a decrease in the level of IgG and IgA (in women of group 2) in the serum against the normal level of B lymphocytes (CD19+ cells). However, these patients showed an increase in the IgM level in the serum, which may be due to the development of anaerobic microflora. After treatment, the number of Lactobacillus spp. and Bifidobacterium spp. in the vagina of women in both comparison groups increased compared to the indicators before treatment. However, the number of these bacteria in the vagina of patients with dysbiosis remained lower compared to patients with BV. In both groups, normalization of the number of obligate anaerobic microorganisms, including G. vaginalis, except for Veillonella spp., was also observed. After treatment, the humoral immune response indicators were normalized as well: the level of serum IgG and IgA increased, and the content of serum IgM decreased. Conclusions. In BV patients, the probiotic «Dialak» normalizes the vaginal microbiota, which was confirmed by increasing the number of Lactobacillus spp. and Bifidobacterium spp. along with decreasing the number of anaerobic microorganisms, including G. vaginalis, against the background of the dynamic disappearance of clinical signs of the disease, as well as restoration to the normal level of indicators of the immunity humoral link. The obtained data indicate the effective therapeutic effect of the probiotic «Dialak» on BV.

Evaluation of Anti-S1 IgA Response to Different COVID-19 Vaccination Regimens.

IgA plays a crucial role in early virus neutralization. To identify the IgA stimulation by COVID-19 vaccine, this study aimed to evaluate the level of anti-S1 IgA in the serum of participants immunized with different COVID-19 vaccination regimens. Sera from 567 eligible participants vaccinated with two, three, or four doses of different types of COVID-19 vaccine were recruited. Post-vaccine anti-S1 IgA responses significantly varied according to vaccine type and regimen. The finding showed that heterologous boosters, especially after priming with an inactivated vaccine, elicited higher IgA levels than homologous boosters. Vaccination with SV/SV/PF produced the highest IgA level among all the immunization regimens after either two, three, or four doses. The different routes and amounts of vaccine used for vaccination showed non-significant differences in IgA levels. After the third dose of immunization for 4 months, the level of IgA decreased significantly from the level found on day 28 in both SV/SV/AZ and SV/SV/PF groups. In conclusion, our study showed that heterologous booster regimens for COVID-19 elicited higher anti-S1 IgA levels in serum, especially after priming with inactivated vaccine. The presented anti-S1 IgA may have advantages in preventing SARS-CoV-2 infection and severe disease.

#3701 MESANGIAL C3 DEPOSITION ASSOCIATES WITH CHRONIC LESIONS AND RENAL OUTCOME IN PATIENTS WITH IGA NEPHROPATHY

Abstract Background and Aims Mesangial C3 deposition is frequently observed in patients with IgA nephropathy (IgAN). We sought to investigate whether the extent of mesangial C3 deposition predicts long-term renal function. Method We conducted a retrospective, observational study that included all patients with biopsy-proven IgAN between 1999 and 2021 and a follow-up period of at least 12 months. All renal biopsy specimens were reviewed and scored according to the 2016 revised Oxford Classification by two independent pathologists. In addition, mesangial C3 deposits were assessed by immunofluorescence (IF) staining of C3 deposition and scored semi-quantitatively as: absent, mild (1+), moderate (2+) and intense (3+). The study composite endpoint was defined as doubling of serum creatinine or ESRD, whichever came first. Results 197 patients were followed for a median of 51.7 months (IQR:19.9-84.3 months). The mean eGFR and median 24-hour proteinuria were 54.4 ± 31.3 ml/min/1.73 m2 and 1.5 g/day (IQR: 0.8-3.35), respectively. 29.9% of the patients reached the composite endpoint. The percentage of patients with M1, E1, S1, T1 and T2 were 77.2%, 24.4%, 57%, 27.9% and 16.8%, respectively. 13.7% of patients showed crescents in less than 25% of glomeruli (C1), while 6.6% of them had over 25% of glomeruli involved (C2). In terms of mesangial C3 deposits, 7.7% had absent, 9.5% mild, 19.6% moderate and 63.1% intense IF staining. Compared to patients with mild-moderate or absent C3 staining on IF, those with intense C3 staining had more frequently M1 (83% vs. 73.5% vs. 38.5%, p = 0.04), S1 (64.2% vs. 49% vs. 30.8%, p = 0.03) and T1-2 (51.9% vs. 32.6% vs. 7.7%, p = 0.01). Similarly, the percentage of global glomerulosclerosis was significantly higher in patients with intense C3 staining (20.7% vs. 12.5% vs. 0%, p = 0.04). In terms of clinical variables, patients with intense C3 staining had a greater degree of proteinuria [1.8 (IQR: 0.9-3.6) vs. 1.2 (0.6-2.1) vs. 0.5 (IQR: 0.1-4.9), p = 0.04] and a tendency for a worse kidney function at baseline (52 ± 32 vs. 58 ± 32 vs. 66 ± 40 ml/min, p = 0.3). There was a tendency for patients with mesangial C3 deposits to have an increased serum IgA level, but the extent of deposits did not correlate with serum C3 level. Regarding the renal outcome, there was a significantly higher proportion of patients with intense C3 deposition to have a doubling of serum creatinine (23.6% vs. 12.2% vs. 0%, p = 0.05) and a tendency for a worse composite endpoint (35.8% vs. 22.4% vs. 23.1%, p = 0.1). Accordingly, the odds ratio for doubling of serum creatinine and for the composite endpoint in patients with intense C3 deposition were 2.88 (95%CI, 1.11-7.47, p = 0.02) and 1.91 (95%CI, 0.94-3.91, p = 0.07), respectively. Conclusion In our study, the extent of mesangial C3 deposition associated with clinical variables and chronic lesions of MESTC score. In addition, identification of intense C3 staining on IF could predict a worse renal outcome in patients with IgA nephropathy.