Immunoglobulin Levels Research Articles

Epigenetic signatures of asthma: a comprehensive study of DNA methylation and clinical markers

BackgroundAsthma, a complex respiratory disease, presents with inflammatory symptoms in the lungs, blood, and other tissues. We investigated the relationship between DNA methylation and 35 clinical markers of asthma.MethodsThe Illumina Infinium EPIC v1 methylation array was used to evaluate 742,442 CpGs in whole blood from 319 participants from 94 families. They were part of the Netherlands Twin Register from families with at least one member suffering from severe asthma. Repeat blood samples were taken after 10 years from 182 individuals. Principal component analysis on the clinical asthma markers yielded ten principal components (PCs) that explained 92.8% of the total variance. We performed epigenome-wide association studies (EWAS) for each of the ten PCs correcting for familial structure and other covariates.Results221 unique CpGs reached genome-wide significance at timepoint 1 after Bonferroni correction. PC7, which correlated with loadings of eosinophil counts and immunoglobulin levels, accounted for the majority of associations (204). Enrichment analysis via the EWAS Atlas identified 190 of these CpGs to be previously identified in EWASs of asthma and asthma-related traits. Proximity assessment to previously identified SNPs associated with asthma identified 17 unique SNPs within 1 MB of two of the 221 CpGs. EWAS in 182 individuals with epigenetic data at a second timepoint identified 49 significant CpGs. EWAS Atlas enrichment analysis indicated that 4 of the 49 were previously associated with asthma or asthma-related traits. Comparing the estimates of all the significant associations identified across the two time points yielded a correlation of 0.81.ConclusionWe identified 270 unique CpGs that were associated with PC scores generated from 35 clinical markers of asthma, either cross-sectionally or 10 years later. A strong correlation was present between effect sizes at the 2 timepoints. Most associations were identified for PC7, which captured blood eosinophil counts and immunoglobulin levels and many of these CpGs have previous associations in earlier studies of asthma and asthma-related traits. The results point to a robust DNA methylation profile as a new, stable biomarker for asthma.

Specific antibody responses to Qβ-displayed Plasmodium falciparum-derived UB05 and MSP3 proteins in mother-neonate couples.

Malaria blood-stage parasite is a critical pathogenic stage responsible for serious adverse outcomes in pregnant women and their neonates. Immunoglobulin G (IgG) antibody responses specific to various asexual blood-stage antigens were well reported in non-pregnant individuals. However, little is still known during placental malaria. To assess the antibody responses specific to Plasmodium falciparum-derived MSP3 and UB05 malaria vaccine candidates in mother-neonate couples, mother's peripheral blood and neonate's cord blood samples were collected at delivery. After malaria diagnostic, plasma levels of IgG and IgG subclass responses specific to UB05, MSP3 and UB05-MSP3 were determined using ELISA. As outcomes, both mothers and neonates had significantly higher IgG responses to UB05 and UB05-MSP3 compared to anti-MSP3 IgG (p < 0.05), irrespective of malaria status. Significant negative correlations were observed between IgG levels specific to the three antigens and parasitaemia (p < 0.01). Anti-UB05 and anti-UB05-MSP3 IgG levels in neonates showed a significant positive correlation with the corresponding mothers' antibodies (rs = 0.25 with p = 0.04; rs = 0.31 with p = 0.01, respectively). UB05MSP3-specific IgG3 and IgG1 subclass responses were significantly higher than the IgG4 subclass (p < 0.01). The neonates IgG1 and IgG3 levels positively correlated with the corresponding antibody subclasses of mothers. These findings suggest an association between UB05 and UB05-MSP3-specific antibody responses and malaria control during pregnancy. Maternal-foetal transfer of MSP3 and UB05-specific IgG occurs during pregnancy, suggesting the interest in the future malaria vaccination strategies in pregnant women to generate early protective immunity in baby against malaria.

Hydrogen Gas Inhalation Alleviates Airway Inflammation and Oxidative Stress on Ovalbumin-Induced Asthmatic BALB/c Mouse Model

Airway inflammatory diseases, such as asthma, are a global public health concern owing to their chronic inflammatory effects on the respiratory mucosa. Molecular hydrogen (H2) has recently been recognized for its antioxidant and anti-inflammatory properties. In this study, we examined the therapeutic potential of H2 in airway inflammation using an ovalbumin (OVA)-induced BALB/c mouse model of allergic asthma. Female BALB/c mice were sensitized and challenged with OVA to induce airway inflammation, and 30 mice were randomly divided into five groups: NT (non-treatment), HTC (3% H2 treatment only), NC (negative control, OVA only), PC (positive control, OVA + intranasal 1 mg/mL salbutamol 50 μL), and HT (H2 treatment, OVA + inhaled 3% H2). Various inflammatory and oxidative stress (OS)-induced markers such as white blood cells (WBCs) and their differential counts, lung histology, cytokine levels such as interleukin (IL)-4, (IL)-5, (IL)-13, interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), granulocyte-macrophage colony-stimulating factor (GM-CSF), (IL)-10, reactive oxygen species (ROS), nitric oxide (NO), glutathione peroxidase (GPx), and catalase (CAT), and total immunoglobulin E (IgE) levels were investigated. Our results showed that inhaled H2 significantly reduced inflammatory cell infiltration, OS markers, and pro-inflammatory cytokine expression while upregulating antioxidant enzyme activity. Furthermore, H2 also significantly decreased serum IgE levels, a marker of allergic inflammation. Collectively, our findings suggest that H2 inhalation is a promising treatment option for airway inflammation, offering a novel approach with potential clinical applications.

Warning values of serum total kappa/lambda ratio for M-proteinemia

BackgroundTo introduce the serum total kappa/lambda ratio (K/L) in humoral immunity testing reports to improve the detection rate of M-proteinemia.Methods156 M protein-positive and 5464 M protein-negative samples confirmed by serum immunofixation electrophoresis(sIFE) were accumulated from January 2021 to December 2023 in the First Affiliated Hospital of Soochow University and the contents of immunoglobulins (IgG, IgA, IgM, kappa and lambda) were tested by Beckman IMMAGE800. All the samples were divided into two groups by time: the modeling group and the validation group. The K/L values in the modeling group were analyzed by SPSS 27.0 to get the receiver operating characteristic curve (ROC). Furthermore, a more in-depth analysis was conducted to verify the reliability of the optimal cutoff values in the validation group. In addition, the levels of immunoglobulins of another group including 106 patients with definite diagnosis of monoclonal gammopathy ranging from January 2021 to June 2024 were traced back to improve the diagnostic efficiency.ResultsThe optimal cutoff values of K/L were 2.31 and 1.43 corresponding to K-type and L-type M-proteinemia respectively by ROC analysis. The sensitivity and specificity were validated as 76.14% and 77.42%. False positives were mainly found in samples with systemic sclerosis (36.84%), hypohepatia (28.71%) and sicca syndrome (27.27%). While false negatives were mainly found in IgA monoclonal gammopathy (38.39%) and IgM monoclonal gammopathy (28.57%). Combining with the detection rules of IgG, IgA and IgM, the sensitivities for the diagnosis of immunoglobulin light chain amyloidosis(AL) and monoclonal gammopathy of undetermined significance(MGUS) can be increased to 83.33% and 85%.ConclusionsK/L > 2.31 and K/L < 1.43 can be used as warning values for M-proteinemia. In addition, the content of the heavy chain in IgA- or IgM-type M-proteinemia may be considered to improve the detection rate.

A Multi-centre Analysis of Serum IgE Levels in Atopic Dermatitis

Abstract Objective: To assess the characteristics of total immunoglobulin E (IgE) and allergen-specific IgE (sIgE) to 20 common allergens in 154 patients with atopic dermatitis (AD). To assess the correlation of clinical food allergy with positive food allergens’ sIgE results. We further discuss the significance of IgE as a potential biomarker for AD disease severity. Methods: A total of 154 AD patients were collected from 15 hospitals nationwide in China from 2019 to 2021. Serum IgE was measured using reverse-enzyme immuno capture test (REAST). Patients were required to have at least one positive sIgE (N ≥ 0.35 IU/mL). Patients were divided into groups according to gender, age, disease severity, and region. SPSS 26.0 software was used for statistical analysis. Results: Compared with adolescent and adult, AD in infancy and childhood showed significantly higher frequencies of positive sIgE to food allergens, including egg, cow milk, and wheat (P &lt; 0.01). However, adolescent and adult AD showed significantly higher frequencies of positive sIgE to inhaled allergens, dermatophagoides farinae, and house dust mite. In addition, sIgE in different sexes were different. Compared with women, men showed higher frequencies of positive allergen-specific IgE level to wheat, dermatophagoides farinae, and house dust mite. The most common food allergens with elevated sIgE levels were egg (71%), cow milk (39%) and wheat (32%). However, AD patients reported seafood, including crab, shrimp, and fish, as the most frequent food allergens which aggravate their disease in their daily life. Only 18 (12%) patients reported definite correlation of clinical practice with positive food allergens’ IgE results. Among 154 sIgE-positive patients, 99 patients had an increase of total IgE (≥60 IU/ml). TotalIgE (tIgE) levels were significantly different between mild (193 ± 239 IU/mL), moderate (170 ± 202 IU/mL), and severe (375 ± 343 IU/mL) forms of AD patients (P &lt; 0.01). AD patients with accompanied allergic diseases showed significantly higher tIgE levels than those without accompanied allergic symptoms (280 ± 286 IU/mL vs 194 ± 248 IU/mL). Conclusion: Neither sIgE nor tIgE levels can be used to evaluate the condition or severity of AD. AD patients with accompanied allergic diseases showed significantly higher tIgE levels than those without accompanied allergic symptoms. Infantile AD patients are more allergic to food, while adolescents and adults are more allergic to environmental antigens. IgE tests must be interpreted by combining with clinical history to avoid unnecessary food avoidance. Early food allergen introduction for infants may be promising for the prevention of food allergies.

Assessment of the humoral immunity against diphtheria, tetanus, and hepatitis B among children with acute lymphocytic leukemia

Background: Approximately all systemic therapies for childhood affect the immune system. The behavior of the immune system in leukemia patients following chemotherapy is not yet clearly defined. The probability of vaccination failure and the need for revaccination remain challenging for these patients. Aim: To evaluate the humoral immunity against diphtheria, tetanus, and hepatitis B in children with acute lymphocytic leukemia (ALL) immediately and 6 months after chemotherapy. Materials and Methods: In the present prospective cohort study, 21 patients with ALL referred to Mofid Children’s Hospital were studied immediately and 6 months after chemotherapy. Serum samples were collected from patients, and the levels of immunoglobulins (IgG, IgM, IgE, and IgA) antibodies against diphtheria, tetanus, and hepatitis B were determined using specific enzymelinked immunosorbent assay kits. The obtained data were analyzed using Statistical Package for Social Sciences 21 software. Results: A total of 13 males and 8 females with an average age of 8.6 ± 2.5 years were included in the present study. Six months after chemotherapy, the mean level of IgG, IgM, IgE, and IgA displayed an increase of 563.1 units in IgG, 11 units in IgM, 11.3 units in IgE, and 5 units in IgA levels. Moreover, data revealed that 6 months after chemotherapy, the mean level of IgG antibodies displayed an increase of 7.09, 3.43, and 1.03 units against hepatitis B, diphtheria, and tetanus, respectively. A significant relationship was found between the antibody level against diphtheria and the age group of the patients (p = 0.003). Conclusion: Humoral immune status was boosted after 6 months of chemotherapy, though all patients had some extent of lasting immune dysfunction. We indicate that survivors of childhood cancer have ongoing humoral immunological defects and may remain at risk for infectious complications after completion of therapy. Relevance for Patients: The present study indicated that systemic therapies for pediatrics with leukemia affect the immune system. Pediatrics with leukemia may remain at risk for infectious complications after completion of therapy.

Bifidobacterium breve M-16V and scGOS/lcFOS Supplementation to Dams Ameliorates Infant Rotavirus Infection in Early Life.

The immune system of newborns is underdeveloped, leaving them susceptible to infections like rotavirus (RV). Despite vaccines, RV remains a leading cause of child mortality, especially in developing countries. Maternal immunity is transferred during pregnancy and breastfeeding to the offspring providing protection against RV infection. This study aims to explore how the maternal diet can enhance the newborn's ability to fight early infections. Pregnant rats received orally Bifidobacterium breve M-16V and short chain galacto-oligosaccharides (scGOS)/long chain fructo-oligosaccharides (lcFOS). At day 5 of life pups are infected with RV and at day 8, samples are collected for the infection analysis. Pups whose mothers received the synbiotic have lower RV infection severity. The levels of immunoglobulins (Ig) IgG2c and IgA are raised in pups' plasma and digested milk, respectively. Synbiotic supplementation improves intestinal maturation and increases gene expression of immune-related genes. In conclusion, the administration of this synbiotic to gestating and lactating mothers ameliorates the incidence and severity of the pup's diarrhea caused by the RV infection by improving their immunity.

IgE immunoadsorption: technical background, functionality, and first clinical experience

Summary Background The prevalence of allergic diseases has risen in the 21st century, drawing attention to specific therapeutic and preventive strategies. Due to the key role of immunoglobulin E (IgE) in the development of allergic reactions, IgE represents a key target treatment. In this scenario, IgE immunoadsorption (IgE-IA) has been investigated as a procedure that selectively removes circulating IgE antibodies from the bloodstream of patients with atopy. Methods This narrative review aims to critically summarize the current insights regarding IgE-IA in the context of the management of allergic diseases, ranging from the rationale to the technical aspects, as well as the benefits and unmet needs. Results IgE-IA might be a treatment strategy in well-selected patients with allergic diseases. IgE depletion through sessions of IgE-IA results in immediate clinical improvement and might be useful in acute situations when a rapid clinical response is required or when classic approaches are contraindicated or ineffective. Due to the reduced effectiveness over time, IgE-IA could be a valid first approach before starting another IgE depletion therapy, such as omalizumab, when its commencement would otherwise be contraindicated by too-high serum IgE levels. Conclusion Overall, IgE-IA is safe and well tolerated; however, this procedure is currently difficult to implement in routine clinical practice because of costs, time demands, need for hospitalization, and the invasiveness of the procedure, with the associated risks related to the necessity of venous catheterization.

Effect of Probiotic Lactobacillus Casei on Secretory Immunoglobulin A (S-IgA) Levels in Rats Norvegicus Strain Wistar Post Ovariectomy

Estrogen promotes the growth of Lactobacillus colonies in the vagina, converting glycogen in superficial cells into lactic acid, resulting in a low vaginal pH that inhibits pathogenic bacteria. Post-menopause, Lactobacillus growth declines, leading to thinner secretions, higher vaginal pH, and a weakened immune system. This study investigates the effect of Lactobacillus casei extract on secretory immunoglobulin A (IgA) levels, vaginal acidity, and beneficial bacteria in the vaginal mucosa. An experimental post-test-only control group design was employed with 24 female rats aged 8-10 weeks, weighing 180-220 grams. Following ovariectomy and a 14-day acclimation, the rats were divided into four groups: a control group (K) with no treatment and three treatment groups (P1, P2, P3) receiving Lactobacillus casei extract at doses of 2ml, 2.25ml, and 2.5ml, respectively, administered orally for 14 days. On day 15, vaginal acidity was measured using a swab method, and IgA levels were assessed via ELISA; gram-positive staining was performed for bacterial identification. One-way ANOVA revealed that Lactobacillus casei extract significantly increased IgA levels and reduced vaginal acidity (p = 0.003 and p = 0.000). The reduction in acidity is attributed to Lactobacillus converting glycogen into lactic acid, maintaining vaginal acidity, while S-IgA on the mucosal surface acts as an opsonin and antigen-presenting cell to inhibit pathogenic growth. The study concludes that Lactobacillus casei extract can elevate secretory IgA levels and normalize vaginal pH.

Влияние избыточной массы тела и ожирения на спирометрические, гематологические показатели, уровень общего иммуноглобулина Е и интерлейкина-6 в сыворотке крови у детей и подростков с бронхиальной астмой

There is undoubtedly insufficient number of studies dedicated to the interleukin-6 (IL-6) in blood serum of children and adolescents with bronchial asthma (BA) and those are contradictory. Connection between the IL-6 serum level and systemic markers of type 2 inflammation in BA in children and adolescents depending on the nutritional status remains a subject to discussion as well. The purpose of this research was to study the effect of excess body weight (BW) and obesity on spirometric, hematological parameters, total immunoglobulin E (IgE), IL-6 levels in blood serum of children and adolescents with BA. Materials and methods used: a single-center observational cross-sectional pilot study of 76 adolescents aged 6 to 17 y/o (75% (57) boys) with BA was conducted. All were measured for anthropometric and spirometric parameters, body composition, hematological parameters, total IgE and IL-6 levels in blood serum. Dysanapsis was diagnosed when three conditions were simultaneously met: 1. high or high-to-normal zFVC (above 0.674), 2. normal zFEV1 (above -1.645), and 3. low FEV1/FVC index (below 80%). Results: the number of monocytes (109/l) in peripheral blood and the serum IL-6 level (pg/ml) were statistically significantly higher in the group of patients with overweight and obesity compared to patients with underweight/normal BW (0.55 [0.49; 0.77] v 0.51 [0.42; 0.58], p=0.043 and 1.99 [1.20; 5.78] v 1.28 [0.31; 2.43], p=0.002, respectively). In patients with excess BW and obesity, an inverse statistically significant relationship was found between the serum IL-6 level, zFEV1/FVC and the dysanapsis ratio (R=-0.53, p=0.009, R=-0.61, p=0.002, respectively). Conclusion: formation of an obstructive pattern in children and adolescents with BA with excess BW and obesity may be associated with non-T2-dependent inflammatory mechanisms.

Electroacupuncture preconditioning prevents urticaria by regulating inflammatory response in rats with urticaria

To observe the effect of electroacupuncture (EA) preconditioning at "Quchi" (LI11) and "Xuehai" (SP10) in prevention of urticaria. Twenty-four male SD rats were randomly divided into control, model and preconditioning of EA (Pre-EA) groups (8 rats/group). The urticaria model was established by intradermal injection of dilute allogeneic antioalbumin serum at the spots of the bilateral symmetry of the spine on the back, and followed by tail venous injection of mixture solution of egg albumin diluent, plus 0.5% Evans blue and normal saline. Ten days before the end of modeling, rats of the pre-EA group received EA stimulation of LI11 and SP10 for 20 min, once a day for 10 consecutive days. The times of rat's scratching the sensitized skin were recorded. HE staining method was used to observe the pathological changes of skin tissue, and toluidine blue staining method was used to observe the morphology of mast cells (MCs) in the skin, blood, mesentery, and peritoneal fluid, and calculate the degranulation rate. Immunohistochemical stainning was used to detect immunoglobulin E (IgE), histamine (HIS), and 5-hydroxytryptamine (5-HT) expressions in subcutaneous tissue. NOD like receptor thermal domain associated protein 3 (NLRP3) inflammasome, apoptosis related granule protein (ASC), and cysteine aspartate aminotransferase 1 (Caspase-1) protein expression levels in skin tissue were detected by Western blot. The contents of serum interleukin(IL)-1β and IL-18 were detected using ELISA method. Compared with the control group, the scratching times, amount of Evans blue exudation of the sensitized blue spots, degranulation rate of MCs in skin, blood, mesentery and peritoneal fluid, the expression levels of IgE, HIS, 5-HT in subcutaneous tissue, protein expression levels of NLRP3, ASC, Caspase-1 in skin tissue, and the contents of serum IL-1β and IL-18 were significantly increased (P<0.01, P<0.05) in the model group. In comparison with the model group, the scratching times, amount of Evans blue exudation of the sensitized blue spots, degranulation rate of MCs, the expression levels of IgE, HIS, 5-HT in subcutaneous tissue, protein expression levels of NLRP3, ASC, Caspase-1 in skin tissue, and the contents of serum IL-1β and IL-18 in EA group were significantly decreased (P<0.01, P<0.05). EA preconditioning at LI11 and SP10 can prevent and treat UR by inhibiting inflammatory response, which is related to the regulation of pyroptosis.

Association of immunoglobulin E levels with glioma risk and survival.

Previous epidemiologic studies have reported an association of serum immunoglobulin E (IgE) levels with reduced glioma risk, but the association between IgE and glioma prognosis has not been characterized. This study aimed to examine how sex, tumor subtype, and IgE class modulate the association of serum IgE levels with glioma risk and survival. We conducted a case-control study using participants from the University of California, San Francisco Adult Glioma Study (1997-2010). Serum IgE levels for total, respiratory and food allergy were measured in adults diagnosed with glioma (n = 1319) and cancer-free controls (n = 1139) matched based on age, sex, and race and ethnicity. Logistic regression was adjusted for patient demographics to assess the association between IgE levels and glioma risk. Multivariable Cox regression adjusted for patient-specific and tumor-specific factors compared survival between the elevated and normal IgE groups. All statistical tests were 2-sided. Elevated total IgE was associated with reduced risk of IDH-wildtype (RR = 0.78, 95% CI: 0.71-0.86) and IDH-mutant glioma (RR = 0.73, 95% CI: 0.63-0.85). In multivariable Cox regression, positive respiratory IgE was associated with improved survival for IDH-wildtype glioma (RR = 0.79, 95% CI: 0.67-0.93). The reduction in mortality risk was significant in females only (RR = 0.75, 95% CI: 0.57-0.98) with an improvement in median survival of 6.9 months (P<.001). Elevated serum IgE was associated with improved prognosis for IDH-wildtype glioma, with a more pronounced protective effect in females than males, which has implications for the future study of IgE-based immunotherapies for glioma.

Immunoparesis recovery in newly diagnosed transplant ineligible multiple myeloma patients, an independent prognostic factor that complements minimal residual disease.

Information on the prognostic value of immunoparesis (IP) recovery in multiple myeloma (MM) patients has been only generated in some observational and retrospective studies. We have evaluated the prognostic impact of IP recovery and its association with minimal residual disease (MRD) in a series of 113 newly diagnosed transplant-ineligible (NDTI) patients, that received fix duration treatment (18 cycles of VMP/lenalidomide-dexamethasone) within the PETHEMA/GEM2010MAS65 trial and who achieved CR or VGPR. Immunoglobulin levels were measured at diagnosis, at the end of treatment (after cycle 18th) and during subsequent follow up whereas MRD was analyzed only at the end of the treatment (after cycle 18th). We found that patients who had IP at diagnosis and recovered it during or after treatment had longer progression free survival (PFS) [p < 0.001; HR 0.32 (0.19-0.52)] and longer overall survival (OS) [p = 0.007; HR 0.40 (0.20-0.80)] compared to those who failed to recover it. When we analyzed IP recovery in MRD negative patients, we found that those cases with IP recovery had longer PFS [p = 0.007; HR 0.31 (0.13-0.76)] and longer OS [p = 0.012; HR 0.21 (0.06-0.80)] as compared to MRD negative patients but without IP recovery. In conclusion, IP recovery confers better prognosis in NDTI-MM patients with fixed duration treatment who achieve CR or VGPR and the prognostic value of MRD can be complemented when combined with IP recovery.

Effects of guanidine acetic acid supplementation from gestation to lactation on reproductive performance, colostrum quality, blood biochemistry, and intestinal microflora diversity of sows

This experiment aimed to study the effects of guanidine acetic acid (GAA) on reproductive performance, lactation performance and blood biochemical indices of sows, as well as the performance of offspring piglets. A total of 20 sows (Landrace × Yorkshire, parity 4) were used. Half of the sows in each parity were fed a control diet (CG; basic diet, n = 10) or GAA diet (basic diet +1 g/kg GAA, n = 10) from the 85th day of gestation until weaning. The study results are presented as follows: Supplementation of GAA from late gestation to lactation did not adversely affect sow feed intake, backfat thickness, or blood routine indexes (p &amp;gt; 0.05). GAA supplementation showed a tendency to increase the number of healthy piglets and their birth activity (p = 0.06; p = 0.08), while significantly increasing the IUGR score of piglets (p &amp;lt; 0.05). GAA supplementation significantly increased colostrum protein content (p &amp;lt; 0.05) and tended to increase daily milk yield in sows (p = 0.07). GAA supplementation increased the level of immunoglobulin A in sow colostrum (p &amp;lt; 0.05) and showed a tendency to increase proline content (p = 0.10). GAA supplementation significantly decreased triglyceride content in sow cord blood (p &amp;lt; 0.05), with no significant effects observed on HDL-C, LDL-C, TC, and GLU (p &amp;gt; 0.05). GAA supplementation significantly increased eNOS levels in sow cord blood (p &amp;lt; 0.05), while showing no significant effects on IL-6 and IL-10 (p &amp;gt; 0.05). GAA supplementation did not significantly affect the α diversity of sow intestinal flora (ACE, Shannon, Chao1, Simpson, observed_otus, pielou_e, and good_cover), but PCoA analysis revealed differences in intestinal flora structure between groups. Additionally, GAA decreased the relative abundance of Sarciha and unidentified_ruminococcaceae and increased the relative abundance of Lactobacillus, Parabacteroides, and Pedobacter in the gut. GAA boosts nitric oxide synthase in sows’ umbilical cord blood, enhancing placental blood vessel development. This improves piglet health and vitality, increases beneficial gut bacteria (Lactobacillus, Parabacteroides, Pedobacter), and raises colostrum protein levels and lactation volume, leading to better piglet growth and performance.

Treatment of refractory immune-mediated necrotizing myopathy with efgartigimod

ObjectiveWe aimed to explore the efficacy and safety of efgartigimod in patients with refractory immune-mediated necrotizing myopathy (IMNM).MethodsThis open-label pilot observational study included seven patients with refractory IMNM, all of whom received intravenous efgartigimod treatment. The clinical response was assessed after 4 weeks of efgartigimod treatment according to the 2016 American College of Rheumatology–European League Against Rheumatism response criteria for adult idiopathic inflammatory myopathy. Serum levels of immunoglobulin as well as anti–signal recognition particle (SRP) and anti–3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) antibodies were measured using enzyme-linked immunosorbent assays and commercial line immunoblot assays. Safety assessments included evaluations of adverse events and severe adverse events.ResultsThe seven patients with refractory IMNM included five cases with anti-HMGCR antibodies and two cases within anti-SRP antibodies. Four of the seven patients achieved clinical responses. The total improvement score for the responders at 4 weeks were 32.5, 40.0, 47.5, and 70.0, and those at 8 weeks were 27.5, 47.5, 57.5, and 70.0. In comparison to the responsive patients, the non-responsive patients had longer durations [8 (-) versus 2 (1–5) years, P = 0.03], and more chronic myopathic features by muscle biopsy (67% versus 0%, P = 0.046). Serum immunoglobulin G levels (11.2 ± 2.5 versus 5.7 ± 2.5, P = 0.007) and anti-HMGCR/SRP antibody levels (97.2 ± 6.9 versus 41.8 ± 16.8, P = 0.002) were decreased after treatment compared with baseline levels. Adverse events were reported in one of the seven patients, who showed mild headache.ConclusionsDespite its small size, our study demonstrated that promoting the degradation of endogenous immunoglobulin G may be effective for patients with IMNM. Efgartigimod may be a promising option for cases of refractory IMNM to shorten duration and minimize chronic myopathic features.

Next-generation IgA-SEQ allows for high-throughput, anaerobic, and metagenomic assessment of IgA-coated bacteria

BackgroundThe intestinal microbiota plays a significant role in maintaining systemic and intestinal homeostasis, but can also influence diseases such as inflammatory bowel disease (IBD) and cancer. Certain bacterial species within the intestinal tract can chronically activate the immune system, leading to low-grade intestinal inflammation. As a result, plasma cells produce high levels of secretory antigen-specific immunoglobulin A (IgA), which coats the immunostimulatory bacteria. This IgA immune response against intestinal bacteria may be associated with the maintenance of homeostasis and health, as well as disease. Unraveling this dichotomy and identifying the immunostimulatory bacteria is crucial for understanding the relationship between the intestinal microbiota and the immune system, and their role in health and disease.IgA-SEQ technology has successfully identified immunostimulatory, IgA-coated bacteria from fecal material. However, the original technology is time-consuming and has limited downstream applications. In this study, we aimed to develop a next-generation, high-throughput, magnet-based sorting approach (ng-IgA-SEQ) to overcome the limitations of the original IgA-SEQ protocol.ResultsWe show, in various settings of complexity ranging from simple bacterial mixtures to human fecal samples, that our magnetic 96-well plate-based ng-IgA-SEQ protocol is highly efficient at sorting and identifying IgA-coated bacteria in a high-throughput and time efficient manner. Furthermore, we performed a comparative analysis between different IgA-SEQ protocols, highlighting that the original FACS-based IgA-SEQ approach overlooks certain nuances of IgA-coated bacteria, due to the low yield of sorted bacteria. Additionally, magnetic-based ng-IgA-SEQ allows for novel downstream applications. Firstly, as a proof-of-concept, we performed metagenomic shotgun sequencing on 10 human fecal samples to identify IgA-coated bacterial strains and associated pathways and CAZymes. Secondly, we successfully isolated and cultured IgA-coated bacteria by performing the isolation protocol under anaerobic conditions.ConclusionsOur magnetic 96-well plate-based high-throughput next-generation IgA-SEQ technology efficiently identifies a great number of IgA-coated bacteria from fecal samples. This paves the way for analyzing large cohorts as well as novel downstream applications, including shotgun metagenomic sequencing, culturomics, and various functional assays. These downstream applications are essential to unravel the role of immunostimulatory bacteria in health and disease.-iBMnzqwvJXR12FS2s7VEFVideo

Nephrotic Syndrome and Recurrent Infection

Nephrotic syndrome is characterized by the leakage of protein from the blood into the urine along with the triad of proteinuria, albuminuria, and peripheral edema. Loss of protein leads to the loss of immunoglobulin and complements. X-linked agammaglobulinemia (XLA), or Bruton disease, is a primary immunodeficiency disease caused by a defect in the development of B cells in the bone marrow and a low serum level of immunoglobulins. The present case involves a 12-year-old boy with nephrotic syndrome, osteomyelitis, and recurrent infections. We discovered that he had XLA. This report underscores the importance of considering inborn errors of immunity in cases of protein loss, such as nephrotic syndrome.

Efficacy of probiotics combined with enteral nutrition therapy on intestinal flora, digestive tract symptoms and endogenous environment in patients with gastric cancer undergoing chemotherapy

Objective: To investigate the effects of probiotics combined with enteral nutrition therapy on intestinal flora, digestive tract symptoms and endogenous environment in patients with gastric cancer undergoing chemotherapy. Methods: In this retrospective study, eighty patients with gastric cancer undergoing chemotherapy admitted to Affiliated Hospital of Hebei University from January 2021 to September 2023 were included and divided into two groups by random number table method: the enteral nutrition group and the probiotics combined enteral nutrition group (n=40 each group). The differences in the number of intestinal flora, nutritional indicators, immune function, endotoxin, D-lactic acid levels between the two groups, and the digestive tract symptoms of the two groups before and after treatment were compared and recorded. Results: The levels of serum total protein (TP), prealbumin (PAB), albumin (ALB) and transferrin (TF) in both groups were higher than those before treatment, and those in the probiotics combined with enteral nutrition group were higher than those in the enteral nutrition group (p&lt; 0.05). The levels of immunoglobulin A (lgA), immunoglobulin M (lgM) and immunoglobulin G (lgG) in the two groups were lower than before treatment, and those in the probiotics combined with the enteral nutrition group were lower than those in the enteral nutrition group (p&lt; 0.05). Conclusion: Probiotics combined with enteral nutrition results in various benefits in the treatment of patients with gastric cancer undergoing chemotherapy, improving immunity, and reducing gastrointestinal symptoms. doi: https://doi.org/10.12669/pjms.40.10.9032 How to cite this: Yang L, Liang Y, Li R, Chen Y, Zhang X. Efficacy of probiotics combined with enteral nutrition therapy on intestinal flora, digestive tract symptoms and endogenous environment in patients with gastric cancer undergoing chemotherapy. Pak J Med Sci. 2024;40(10):2344-2349. doi: https://doi.org/10.12669/pjms.40.10.9032 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Effects of Boron Supplementation in Dairy Cow Close-Up Rations on Colostrum Quality and Certain Blood Metabolites in Calves.

In this study, we aimed to investigate the effects of different levels of boron supplementation to the diet during the close-up period and the first postpartum day on postpartum colostrum quality, immunoglobulin levels in colostrum, and certain calf blood parameters in dairy cattle (n = 21). Two experimental groups and one control (C) group were formed. Boron at 300ppm (T-300) and 600ppm (T-600) was added to the experimental rations. The daily dry matter intake (DMI), body condition score (BCS) of dairy cattle, and body weight (BW) of calves were recorded. Colostrum samples were collected during the first 2 postpartum milkings, and their components were determined. Blood samples were collected from calves at 24 and 48hours after colostrum feeding. The addition of boron to rations during the close-up dry period increased the DMI of cows and the BW of calves born to the T-600 group (p < 0.05). The addition of boron to the rations changed the total protein (TP) and nonesterified fatty acid (NEFA) values in the calf blood samples taken 48hours after birth from those of the control group (p < 0.05). The differences between the blood boron values of the experimental and control groups at 24 and 48hours after colostrum and colostrum feeding were significant (p < 0.05). At the first milking after birth, the colostrum DM value and density were highest in the T-600 group (p < 0.05). In conclusion, due to the high density value of colostrum according to the quality classification of colostrum in the first postpartum milking and the increase in calf blood IgG levels at 48 hours compared to the control group, it may be considered to add up to 600 ppm boron to the rations of cows close-up period in order to improve calf health and prevent calf losses due to colostrum quality.

Immunological Changes and Complement Proteins in Major Thalassemia Patients Proteins Post-Splenectomy

Background: Thalassemia is one of the most prevalent genetic disorders worldwide, with infections being a leading cause of mortality due to compromised immune function. Specific Background: Prior studies suggest that major thalassemia patients are highly susceptible to microbial infections, possibly due to altered immunological profiles, particularly immunoglobulin (IgG, IgM) and complement (C3, C4) levels. Knowledge Gap: However, the specific immunological changes pre- and post-splenectomy in these patients remain underexplored. Aims: This study aims to assess the levels of immunoglobulins (IgG and IgM) and complement proteins (C3 and C4) in major thalassemia patients both before and after splenectomy compared to healthy controls. Results: Our analysis of 50 thalassemia patients (34 males, 16 females) and 30 healthy individuals revealed that thalassemia patients exhibited significantly lower levels of C3 and C4 (88.52±24.49, 21.20±6.66) compared to healthy controls (123.50±19.04, 32.87±9.77). IgG and IgM were elevated in patients (1288.12±467.87, 153.46±51.29) compared to controls (1129.93±295.96, 148.67±50.17). Post-splenectomy, patients showed a significant decline in IgG (1001.56±154.14) and IgM (110.08±25.83) levels, along with further decreases in C3 (83.28±24.13) and C4 (17.48±4.86). Novelty: This study provides novel evidence of the immunological shifts in thalassemia patients post-splenectomy, demonstrating significant reductions in both immunoglobulins and complement proteins, thereby elevating the risk of infection. Implications: These findings highlight the spleen's crucial role in maintaining immune competence and suggest that splenectomy in thalassemia patients requires careful post-operative immune monitoring to mitigate infection risks. Highlights: Splenectomy lowers IgG, IgM, C3, and C4 levels in thalassemia patients. Post-splenectomy patients face higher infection risk due to immune weakening. Highlights spleen's crucial role in immune defense for thalassemia patients. Keywords: Thalassemia, Splenectomy, Immunoglobulins, Complement Proteins, Immune Competence