Immunoglobulin Levels Research Articles

Assessing human B cell responses to influenza virus vaccines and adjuvants in a PBMC-derived in vitro culture system

In vitro systems based on human peripheral blood mononuclear cells (PBMCs) can bridge the gap between preclinical and clinical vaccine evaluation but have so far mainly been exploited to assess vaccine effects on antigen-presenting cells and T cells. Our study aimed to assess whether B cells present in PBMCs also respond to vaccines and reflect the effects of different vaccine formulations and adjuvants. We stimulated PBMCs with whole inactivated virus (WIV) or split virus (SIV) H5N1 influenza vaccine, with or without the addition of the adjuvant cytosine phosphoguanine (CpG) ODN 2395, and collected the cells and supernatants at different timepoints. B cell subsets were measured by flow cytometry, immunoglobulin (IgG) levels by ELISA, B cell-related genes by qPCR, and cytokine levels by intracellular staining. B cells differentiated more readily to plasmablasts and plasma cells and produced more IgG when PBMC cultures were stimulated with WIV than when stimulated with SIV. In line, PRDM1, XBP1, and AICDA, genes associated with the differentiation of B cells to antibody-secreting cells, were expressed at higher levels in WIV- than in SIV-stimulated PBMCs. The combination of WIV and CpG consistently induced the highest levels of antibody-secreting cell differentiation, IgG production, and B-cells secreting IL-6 and IL-10. Taken together, B cells in human PBMC cultures show distinct responses to different types of vaccines and vaccine/CpG combinations. This underlines the suitability of unfractionated PBMCs for evaluating vaccine effects on different types of human immune cells before running costly clinical trials.

EBNA-1 and VCA-p18 immunoglobulin markers link Epstein-Barr virus immune response and brain’s myelin content to fatigue in a community-dwelling cohort

Given the association of Epstein-Barr virus (EBV) with subjective perception of fatigue and demyelination in clinical conditions, the question about potential subclinical effects in the adult general population remains open. We investigate the association between individuals’ EBV immune response and perceived fatigue in a community dwelling cohort (n=864, age 62 ± 10 years old; 49% women) while monitoring brain tissue properties. Fatigue levels are assessed with the established fatigue severity scale, the EBNA-1 and VCA p18 immunoglobulin G (IgG) chronic response – with multiplex serology and the estimates of local brain volume, myelin content, and axonal density - using relaxometry- and multi-shell diffusion-based magnetic resonance imaging (MRI). In our analysis we adjust for the effects of demographic and cardiovascular risk factors, sleep apnea, depression, and polygenic risk score for multiple sclerosis. We demonstrate that EBNA-1 IgG levels are positively associated with perceived levels of fatigue, whilst VCA p18 IgG levels show a positive correlation with myelin content and a negative one with an estimate of axonal g-ratio in male participants. In the context of EBVs immune response, the polygenic risk for multiple sclerosis is not associated with increased fatigue levels, brain myelination or atrophy. Our findings bring empirical evidence about the potential role of EBVs chronic immune response in perceived fatigue and hint towards a protective role of myelination specific for men. They underscore the added value of advanced assessment of brain tissue microstructure in uncovering the mechanisms behind frequent fatigue complaints associated with EBV infection and multiple sclerosis.

Dietary sanguinarine supplementation improves the growth performance and intestinal immunity of broilers

Dietary sanguinarine (SAN) can enhance the growth performance of poultry and livestock, but the regulatory mechanism of the SAN monomer on intestinal homeostasis and how it promotes growth performance has not yet been clarified. In this study, 200 chickens were divided into four groups and fed different doses of SAN (0, 0.225, 0.75, 2.25mg/kg) for transcriptome and microbiota analysis. The data showed that different doses of SAN supplementation increased the feed conversion rate (FCR) of 22 to 42 d old and 1 to 42 d old broilers (P < 0.01), and 0.225 mg/kg SAN reduced the contents of alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine (CREA) and blood urea nitrogen (BUN) in serum (P < 0.01). Dietary SAN increased the villus height and the villus height/crypt depth (V/C) ratio in the ileum (P < 0.01). The levels of tight junction proteins (zonula occludens-1, occludin and claudin-1) were up-regulated in the ileum and cecum (P < 0.01) and the levels of immunoglobulin (Ig) A, IgM, IgG, interleukin (IL)-4, IL-10 and interferon (IFN)-γ were up-regulated in the serum and ileum (P < 0.01). RNA-seq analysis revealed 385 differentially expressed genes (DEGs) (|log2 fold change| ≥ 1, FDR < 0.05) between the SAN group and CON group. Kyoto Encyclopedia of Genes and Genomes pathway analysis showed 15 pathways mostly associated with the immune system. Additionally, the reverse transcription-PCR results showed that the relative mRNA expression of β-defensin and mucin 2 were up-regulated (P < 0.01) and Toll-like receptor (TLR) 2 and TLR 4 mRNA were down-regulated by SAN (P < 0.01), which was consistent with the transcriptomic analysis. Western blot analysis also showed that SAN reduced the expression of inflammatory proteins such as TLR4, nuclear factor-kappa B and IL-1β in the ileum (P < 0.01). In addition, at the genus level, SAN significantly increased the relative abundance of bacteria (Bacteroides, unclassified_f__Lachnospiraceae, Lactobacillus and Romboutsia) involved in acetate and butyrate production in the cecum, which are associated with enhanced intestinal immune function and maintaining intestinal health. In conclusion, SAN ameliorates the growth performance of broilers, enhances intestinal immune function, regulates the structure of microbiota and maintains intestinal health.

Estimation of Resistin and Immunoglobulins (IgA and IgM) Levels in the Serum of Iraqi Patients with Type 1 and Type 2 DiabetesMellitus

Resistin (RE) is a cysteine rich polypeptide. It has been established that in humans adipocytes, pancreatic cells, muscle, and mononuclear cells all express this 108 amino acid polypeptide. It is important to note that resistin is primarily produced by peripheral blood mononuclear cells (PBMCs) in humans. Its part in the inflammatory processes has been proven. Immunoglobulins IgA and IgM are crucial elements of humoralimmunity. They increase inflammatory responses and the removal of immunological complexes by activating the complement system, sensitizing natural killer cells, phagocytes, and mast cells, and regulating cytotoxic cellular activity. The aim of this study was to determine resistin and immunoglobulin IgA and IgM levels in the serum of type 1 diabetic (T1DM) and type 2 diabetic (T2DM) patients and the healthy control. This respective study was carried out at the National Center for Diabetes Treatment and Research and the consulting clinics in Al-Muqdadiya District and Baquba District in Iraq during the period from January 2022 to April 2022. It included 153 participants; divided into 3 groups (51 patients with T1DM and 52 patients with T2DM, and 50 healthy control). The result of serum resistin showed that there was a highly significant difference when comparing the mean of serum resistin of T1DM with that of T2DM patients group and the control group. While no significant difference was detected when the mean of serum resistin ofthe T2DM patients group with that of the control group was compared. The mean of immunoglobulins IgA and IgM were compared in T1DM , T2DM patients and the healthy controls with significant differences between the three groups. It can, therefore, be concluded that increased serum resistin levels were recorded in T1DM patients than T2DM patients and healthy control. Increased serum immunoglobulins IgA and IgM levels were also noticed in T1DM and T2DM patients compared with control.

Synergistic fermentation of Cordyceps militaris and herbal substrates boosts grower pig antioxidant and immune function

BackgroundPathogenic infections can significantly impact the health of livestock. Traditionally, antibiotic growth promoters (AGPs) have been used in feed to enhance growth performance and disease control. However, concerns regarding antibiotic resistance have led to the exploration of traditional herbal medicine as a natural alternative, guided by the principle of medicine-food homology. The Taguchi method was employed to optimize the culture formula for cordycepin production, an active component of Cordyceps militaris (C. militaris). The influences of C. militaris supplementing solid-state fermentation (CMSSF) in feed on the growth performance and immune responses of grower pigs were evaluated in the present study.ResultsThe C. militaris ethanol extract (CME) displayed potent free radical scavenging activity against 2, 2-Diphenyl-1-picrylhydrazyl (DPPH) and 2,2’-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) after undergoing fermentation. Additionally, the antibacterial testing revealed that CME effectively inhibits the growth of common pig pathogens such as Glaesserella parasuis, Pasteurella multocida, Staphylococcus hyicus, and Streptococcus suis. In lipopolysaccharide (LPS)-treated intestinal porcine enterocyte cell line (IPEC-J2), CME significantly suppressed the production of pro-inflammatory cytokines, including tumor necrosis factor (TNF)-α and interleukin (IL)-6. In addition, higher antioxidative activity was detected as indicated by elevated concentration of superoxide dismutase (SOD) in pig serum. The levels of immunoglobulin M (IgM), IgA, and IgG antibodies, as well as classical swine fever virus (CSFV) antibodies (S/P ratio) in serum were all increased. Growth performance of pigs fed with dietary CMSSF supplementation was improved in comparison with the control.ConclusionsResults demonstrated that CMSSF has the potential to be used as a natural growth promoter to enhance immunity, antioxidation, as well as overall health and growth performance of grower pigs.

Efficacy of ofatumumab combined with corticosteroids in the treatment of autoimmune encephalitis: a 6-month cohort study.

This study investigated the efficacy of ofatumumab (OFA) combined with corticosteroids in autoimmune encephalitis (AE) patients refractory to conventional treatment. Eighteen AE patients admitted to Ruijin Hospital between June 2022 and September 2023 received four subcutaneous 20-mg OFA injections at 0, 1, 6, and 12 weeks combined with standard corticosteroid therapy. Clinical symptoms, modified Rankin scale (mRS) scores, Clinical Assessment Scale for Autoimmune Encephalitis (CASE) scores, serum immunoglobulin (Ig) levels (IgG and IgM), and peripheral blood CD20 + B cell levels were documented before OFA administration and at 1, 2, 6, 12, and 24 weeks post-treatment. OFA treatment significantly improved psychiatric symptoms (P = 0.025), cognitive dysfunction (P = 0.008), and seizure frequency (P = 0.014). The mRS and CASE scores improved after two injections in patients with anti-NMDAR encephalitis (P = 0.041), but not in patients with anti-LGI1 encephalitis (P > 0.05). The mRS scores significantly improved at 12 weeks post-treatment in antibody-negative encephalitis. Blood CD20 + B cell levels dropped to zero after an average of 2.5 injections. No significant changes could be observed in serum IgG and IgM levels (P > 0.05). Seven patients had mild fever or pulmonary infections post-treatment. This study suggests that OFA is a safe and effective treatment for a subset of AE patients, particularly in cases of anti-NMDAR encephalitis, though further research is needed on long-term outcomes and recurrence.

Effect of Blood Orange (Citrus sinensis L. Osbeck) Peel Waste as a Feed Additive on the Growth Performance, Digestive Enzyme Activity, Antioxidant Capacity, and Immune Response in Juvenile Black Rockfish (Sebastes schlegelii)

This study evaluated bioactive compounds in blood orange (Citrus sinensis (L.) Osbeck) peel (BOP) as dietary additives. An 8-week feeding trial was conducted to investigate the effects of dietary supplementation on the growth performance, body composition, digestive enzyme activity, antioxidant capacity, and immune response of juvenile black rockfish. A total of 1260 juvenile rockfish (1.4 ± 0.01 g) were randomly distributed into seven treatment groups, each with 50 fish per circular tank. The groups were fed seven different diets containing graded levels of 0 (control, BOP0), 1 (BOP1), 2 (BOP2), 3 (BOP3), 5 (BOP5), 7 (BOP7), and 10 (BOP10) g kg−1, respectively. The BOP10 diet significantly enhanced the final weight, weight gain, specific growth rate, protein efficiency ratio, and protein retention in fish. The BOP treatments notably affected the fishes’ whole-body crude protein and lipid contents. Plasma total cholesterol levels of fish fed the BOP0 and BOP1 diets were significantly higher than those fed the BOP7 and BOP10 diets. The activities of trypsin and lipase were significantly affected by dietary BOP levels. The antioxidant enzyme activity in the plasma of fish fed the BOP10 diet was significantly higher than those fed the BOP0 diet. The lysozyme activity and levels of immunoglobulin M and G in fish fed the BOP0 diet were significantly lower than those in fish fed the BOP10 diet. In conclusion, dietary supplementation of BOP at 10 g kg−1 improved the growth performance and overall health of juvenile black rockfish.

Current and emerging tools for simultaneous assessment of infection and rejection risk in transplantation

Infection and rejection are major complications that impact transplant longevity and recipient survival. Balancing their risks is a significant challenge for clinicians. Current strategies aimed at interrogating the degree of immune deficiency or activation and their attendant risks of infection and rejection are imprecise. These include immune (cell counts, function and subsets, immunoglobulin levels) and non-immune (drug levels, viral loads) markers. The shared risk factors between infection and rejection and the bidirectional and intricate relationship between both entities further complicate transplant recipient care and decision-making. Understanding the dynamic changes in the underlying net state of immunity and the overall risk of both complications in parallel is key to optimizing outcomes. The allograft biopsy is the current gold standard for the diagnosis of rejection but is associated with inherent risks that warrant careful consideration. Several biomarkers, in particular, donor derived cell-free-DNA and urinary chemokines (CXCL9 and CXCL10), show significant promise in improving subclinical and clinical rejection risk prediction, which may reduce the need for allograft biopsies in some situations. Integrating conventional and emerging risk assessment tools can help stratify the individual’s short- and longer-term infection and rejection risks in parallel. Individuals identified as having a low risk of rejection may tolerate immunosuppression wean to reduce medication-related toxicity. Serial monitoring following immunosuppression reduction or escalation with minimally invasive tools can help mitigate infection and rejection risks and allow for timely diagnosis and treatment of these complications, ultimately improving allograft and patient outcomes.

Fc-Afucosylation of VAR2CSA-Specific Immunoglobulin G and Clinical Immunity to Placental Plasmodium falciparum Malaria.

Acquired immunity to Plasmodium falciparum malaria is mainly mediated by immunoglobulin G (IgG) targeting erythrocyte membrane protein 1 (PfEMP1). These adhesins mediate infected erythrocyte (IE) sequestration, protecting IEs from splenic destruction. PfEMP1-specific IgG is therefore thought to protect mainly by inhibiting IE sequestration. VAR2CSA-type PfEMP1 mediates placental IE sequestration, putting pregnant women exposed to P falciparum parasites at risk of placental malaria (PM). Levels and Fc-afucosylation of VAR2CSA-specific plasma IgG were measured by a modified enzyme-linked immunosorbent assay (FEASI). We also measured the ability of the IgG to inhibit IE adhesion and to induce natural killer (NK) cell degranulation. The results were related to parity and clinical pregnancy outcomes. Parity was positively correlated with levels and Fc-afucosylation of VAR2CSA-specific IgG, and with birth weight and plasma IgG inhibition of IE adhesion in vitro. Fc-afucosylation of VAR2CSA-specific IgG increased NK-cell degranulation. Women with Fc-afucosylated VAR2CSA-specific IgG had a reduced risk of delivering a low birth weight (LBW) baby, but not of PM or anemia. Fc-afucosylated VAR2CSA-specific IgG effectively induced NK-cell degranulation and was associated with protection against LBW, independent of IgG levels. Our study has implications for the development of VAR2CSA-based subunit vaccines, which exclusively induce Fc-fucosylated IgG.

Immunological Responses, Expression of Immune-Related Genes, and Disease Resistance of Rainbow Trout (Oncorhynchus mykiss) Fed Diets Supplied with Capsicum (Capsicum annuum) Oleoresin

A 45-day feeding study was carried out to assess the immune-stimulatory effects of capsicum oleoresin when added to rainbow trout diets. A total of 450 fish (mean weight: 155.20 ± 1.96 g) were distributed into 400 L tanks (30 fish/tank) across five experimental groups: control (CT, 0%), C7 (0.7%), C14 (1.4%), C21 (2.1%), and C28 (2.8%). Each group consisted of three replicate tanks. At the end of this period, hemato-biochemical parameters, innate immune responses, and immune-related gene expression levels were evaluated, and a histological examination of head kidney and liver sections was conducted. Finally, fish in all groups were challenged with Lactococcus garvieae and observed for an additional 20 days. The results revealed that oleoresin supplementation enhanced the immune responses of the treated fish, which was evidenced by the increased globulin, total protein, respiratory burst activity, and total immunoglobulin levels. The highest expression levels of the il-8, il-1β, TGF-β, and SAA genes was noticed in the C7 group, as compared with the results for the other groups. The IgT gene expression levels were higher in all experimental groups than in the CT group, and this increase was at the highest level in the C28 group. Following the bacterial challenge, all experimental groups displayed higher survival rates compared to that of the CT group. These values were 75.93, 72.22, 46.30, 33.33, and 29.63% in the C7, C14, C21, C28, and CT groups, respectively, with the C7 group displaying the highest survival rate among the groups. The histological examination of liver and head kidney tissues revealed that higher doses (in the C21 and C28 groups) showed an increase in cytoplasmic vacuolization, which causes adverse effects on fish health. However, the C7 group displayed normal histological structure in both tissues. Taken together, the most favorable immune responses were achieved in the C7 group, suggesting that 0.7% oleoresin could be applied to rainbow trout to boost immunity and protect the fish from diseases.

Characteristics of patients with low serum IgE levels and selective IgE deficiency: Data from an immunodeficiency referral center

Low immunoglobulin E (IgE) levels are defined as values below 2.5 IU/mL. Selective IgE deficiency (sIgED) refers to reduced serum IgE levels in patients with normal IgA/G/M levels. We evaluated 677 patients with low IgE levels. Recurrent infections (78.8 %), a history of allergy (27.3 %), and autoimmune/inflammatory diseases (18.3 %) are common. The primary immunodeficiency disease (PID) (n = 483, 71.3 %) diagnoses include 313 (46.2 %) patients with antibody deficiency and 119 (17.6 %) with combined immunodeficiency. Genetic pathogenic variants were present in 154 out of 207 PID patients. Within sIgED group, 23 (19.8 %) had primary immunodeficiencies. We observed a high prevalence of autoimmune/inflammatory diseases, allergies, malignancies, and PID among patients with low IgE levels. Therefore, clinicians should be vigilant when evaluating patients with low IgE levels, as this finding may indicate an underlying systemic disease or PID.

Dietary 25-Hydroxycholecalciferol Supplementation from Day 85 of Gestation to Farrowing Enhances Performance, Antioxidant Capacity, and Immunoglobulins of Sows and Newborn Piglets

In this study, the aim was to evaluate the effects of dietary 25-hydroxycholecalciferol supplementation from day 85 of gestation on performance, antioxidant capacity, and immunoglobulin level of sows and newborn piglets. On day 85 of gestation, forty Landrace × Yorkshire gestating sows (average body weight of 241 ± 6.8 kg; average parity of 3.47 ± 0.6) were allotted into two treatments (20 replicates per treatment) based on parity, body weight, and back fat thickness. From day 85 of gestation to farrowing, sows were fed a normal vitamin D3 diet as control (containing 50 μg/kg vitamin D3; CON), or a 25-hydroxycholecalciferol-supplemented diet (containing 50 μg/kg 25-hydroxycholecalciferol). Compared with CON, dietary 25-hydroxycholecalciferol supplementation increased (p &lt; 0.05) protein and fat content in colostrum and the average birth body weight of newborn piglets. Sows fed 25-hydroxycholecalciferol showed increased (p &lt; 0.05) apparent total tract digestibility of crude protein compared with CON. Diets supplemented with 25-hydroxycholecalciferol also increased (p &lt; 0.05) the content of superoxide dismutase (SOD), and tended to increase (p = 0.06) the total antioxidant capacity content and reduce (p = 0.09) the malondialdehyde (MDA) level in colostrum. An increase (p &lt; 0.05) in the content of SOD and a reduction (p &lt; 0.05) in the content of MDA in the serum of newborn piglets was also observed in the 25-hydroxycholecalciferol treatment compared with CON. Dietary 25-hydroxycholecalciferol supplementation also enhanced (p &lt; 0.05) the immunoglobulin G content and reduced (p &lt; 0.05) the concentration of tumor nuclear factor-α in the serum of sows, as well as reducing (p &lt; 0.05) the content of immunoglobulin G and immunoglobulin A in the serum of newborn piglets compared with CON. Supplementation of 25-hydroxycholecalciferol in sow diets increased (p &lt; 0.05) the content of alkaline phosphatase in the serum and colostrum of sows, the concentration of insulin and crosslap in serum of sows, and the serum calcium content of newborn piglets compared with CON. In conclusion, dietary 25-hydroxycholecalciferol supplementation from day 85 of gestation could enhance performance, antioxidant capacity, and immunoglobulin in sows and newborn piglets.

Protective effect of Curcuma longa L. leaves and pseudostems extract against 1-chloro-2,4-dinitrobenzene-induced atopic dermatitis in BALB/c mice

Ethnopharmacological relevanceThe perennial herbaceous plant, Curcuma longa L. (turmeric) is primarily grown and harvested for pharmacological purposes in China, Korea, and various tropical regions in South Asia. Turmeric has been used for centuries as an indigenous medicine. In particular, Ayurveda has been extensively used to treat, prevent, and manage multiple illnesses, including inflammation, allergies, arthritis, cancer, diabetes, diarrhea, psoriasis, and digestive issues. Importantly, various studies have confirmed the presence of numerous active compounds with health-enhancing biological properties in turmeric leaves and pseudostems. Aim of the studyAtopic dermatitis (AD) is a long-lasting inflammatory disorder that is associated with abnormalities in the immune system, such as T-helper (Th) cell dysregulation, elevated immunoglobulin (Ig) levels, inflammatory cell infiltration, and skin barrier damage. This study aimed to explore the therapeutic effects of turmeric leaves and pseudostems (CLHW) extract against AD in a BALB/c mouse disease model established using 1-chloro-2,4-dinitrobenzene (DNCB). Materials and methodsAD-like symptoms were induced by topically applying DNCB to the dorsal skin of the mice, which were monitored over five weeks. Fourteen days after induction, the mice were randomly divided into different groups, and the treatment groups received daily oral gavage of CLHW for three weeks. Throughout the monitoring period, we assessed AD-like symptoms, including skin severity score, transepidermal water loss (TEWL), and scratching behavior of the mice. After measuring the body weight and ear thickness, the mice were euthanized. Furthermore, serum Ig and cytokine production levels were measured. Finally, the degrees of spleen and lymph node enlargement were evaluated, and the tissues were used for histopathological and molecular analyses. ResultsCLHW improved AD-like symptoms, including skin severity score, TEWL, scratching frequency, and ear thickness in DNCB-induced AD mice. Additionally, serum levels of IgE, IgG1, and IgG2a, along with various inflammatory cytokines (interleukin [IL]-4, IL-5, and IL-13) and chemokines (Eotaxin and RANTES), were significantly reduced in CLHW-treated mice. CLHW decreased inflammatory cell infiltration and mast cell degranulation while downregulating mRNA expression levels of AD-related innate cytokines (thymic stromal lymphopoietin [TSLP], IL-25, IL-33), inflammatory cytokines (IL-4, IL-10, IL-13), and chemokines (thymus and activation-regulated chemokine [TARC], macrophage-derived chemokine [MDC]) in the dorsal skin. Furthermore, CLHW reduced spleen and lymph node enlargement and downregulated mRNA expression levels of inflammatory cytokines in these tissues in a dose-dependent manner. ConclusionThe results demonstrated that CLHW can effectively suppress DNCB-induced AD-like symptoms by reducing the skin severity score, TEWL, scratching, ear thickness, serum Ig levels, inflammatory cell infiltration, and degranulation of mast cells, as well as the enlargement of the spleen and lymph nodes. Our findings highlight the ethnopharmacological potential of CLHW for treating abnormal immune responses associated with AD.

IFN-associated B cell hyperactivity is highly enriched in SLE patients harboring Sm/RNP antibodies.

ABSTRACTSystemic Lupus Erythematosus (SLE) is an autoimmune disease characterized by an array of autoantibodies, in particular anti-nuclear antibodies (ANA). The disease is also hallmarked by an expansion of plasmablasts (PB) in peripheral blood. How these relate to autoantibody production is not clear. Here, we aimed to understand B cell alterations in SLE and their relationship to immunoglobulin levels and autoantibody production.We demonstrate that a subgroup of SLE patients is characterized by a high frequency of PB relative to memory B cells (high PB/M). Patients with this phenotype more frequently had high disease activity. Despite low overall frequencies of memory B cells, these patients exhibited an increased activation in the switched CD27+ memory compartment and a strong IFN signature in PB. Repertoire analysis revealed a highly polyclonal expansion and enrichment for IgG1 expressing PB in patients with a high PB/M ratio which was reflected in increased serum IgG levels. Importantly, the hyperactive B cell phenotype was highly enriched in patients harboring Sm/RNP autoantibodies (OR: 9.17 (2.97-26.0)). In summary, we show for the first time a direct relationship between IFN and PB expansion in a subgroup of SLE patients, highly enriched in those harboring Sm/RNP antibodies. These results provide insight into the pathways leading to B cell hyperactivity and autoantibody production which may guide the tailoring of B cell- and IFN-targeted therapies.Graphical abstract

Efficacy of Pulmicort Respules Combined with Azithromycin in the Treatment of Children with Recurrent Respiratory Tract Infection Caused by Mycoplasmal Pneumonia.

Aims/Background The drug treatment of recurrent respiratory tract infection caused by mycoplasma pneumonia (MP) has a complex background, involving the characteristics of pathogens, drug resistance, and multiple treatment methods. This study aimed to analyze the therapeutic effect of pulmicort respules and azithromycin on children with recurrent respiratory tract infection caused by MP. Methods The clinical data of 106 children with recurrent respiratory tract infection caused by MP diagnosed in Huoqiu First People's Hospital from July 2021 to July 2023 were retrospectively analyzed. Based on different therapeutic methods, 56 children treated with azithromycin were included in the reference group, and 50 children treated with pulmicort respules and azithromycin were included in the observation group. The disappearance time of clinical symptoms, levels of inflammatory factors, immunoglobulin levels, and complications in both groups were observed and compared. Results After treatment, the disappearance time of fever, cough, pulmonary rales, and expectoration was shorter in the observation group, compared with the reference group (p < 0.001). No significant difference was observed in levels of tumor necrosis factor-α (TNF-α), interleukin-2 (IL-2), or interleukin-6 (IL-6) between the two groups on the first day of admission (p > 0.05). After 1 week of treatment, the observation group had significantly higher levels of TNF-α, IL-2, and IL-6 compared with the reference group (p < 0.05). No significant difference was observed in levels of immunoglobulin G (IgG), immunoglobulin A (IgA) and immunoglobulin M (IgM) between the two groups on the first day of admission (p > 0.05). After 1 week of treatment, the observation group had significantly lower levels of IgG, IgA, and IgM than the reference group (p < 0.01). This study revealed that the incidence of complications in the observation group was 16.00%, which was significantly lower than the 37.50% in the reference group (p < 0.05). Conclusion In the short-term clinical treatment, the combination application of pulmicort respules and azithromycin can effectively improve the immune function of children with recurrent respiratory tract infection caused by MP and relieve their clinical symptoms.

Effects of dietary Brassica rapa L. polysaccharide on growth performance, immune and antioxidant functions and intestinal flora of yellow-feathered quail

This study aimed to explore the impact of Brassica rapa L. polysaccharides (BRP) on the growth, immune response, antioxidant capacity, and cecal microbiota in yellow-feathered quails. A total of 250 one-day-old yellow-feathered quails, evenly divided by sex, were randomly assigned to five groups, with each group comprising ten replicates of five quails each. The control group (CON) received a basic diet, while the antibiotic control group (CTC) was fed a basic diet supplemented with chlortetracycline (0.05 g/kg). BRP was administered at concentrations of 0.25 g/kg (Low dose BRP, LBRP), 0.5 g/kg (Medium dose BRP, MBRP), and 1 g/kg (High dose BRP, HBRP). The duration of the experiment was 42 days. The results indicated that, compared to the CON group, the final body weight of quails in the MBRP group significantly increased (P < 0.05), and there was a significant difference in body weight between the LBRP group and the CTC group (P < 0.05). At 21 days of age, the average weights of the thymus and bursa of Fabricius in the MBRP group were significantly greater than those in the CON group (P < 0.05), with no significant difference observed when compared to the CTC group (P > 0.05); at 42 days of age, the average weight of the thymus in the MBRP group was significantly greater than that in the CON group (P < 0.05), with no significant difference observed compared to the CTC group (P > 0.05). At 21 days of age, the levels of IgA and IgG in the MBRP group were significantly elevated compared to the CON group (P < 0.05), with no significant difference noted compared to the CTC group (P > 0.05). Additionally, the MBRP group showed significant increases in CAT, T-SOD, and GSH-Px levels (P < 0.05) compared to the CON group; the levels of IL-1β and TNF-α were significantly reduced (P < 0.05), and the level of IL-10 was significantly elevated (P < 0.05) compared to the CON group. Furthermore, 16 S rRNA sequencing revealed that BRP supplementation increased the populations of beneficial cecal bacteria such as Lactococcus, Weissella, Parabacteroides, and norank_f_Ruminococcaceae, and decreased the population of the harmful bacterium Campylobacter, indicating that BRP modulates the microbial community structure in the cecum of yellow-feathered quails. In summary, BRP enhanced the growth performance, serum immunoglobulin levels, antioxidant functions, and improved the intestinal microbiota in yellow-feathered quails.

Analytical interference on measurement of immunoglobulins in monoclonal gammopathy

Monoclonal gammopathy has been reported to interfere with several laboratory measurement results. We investigated potential interference in monoclonal gammopathy on immunoglobulin A (IgA), immunoglobulin G (IgG), and immunoglobulin M (IgM) concentrations using three different routine chemistry instruments: Alinity (Abbott Laboratories), Cobas 8000 (Roche Diagnostics) and Optilite (Binding Site) at the Department of Clinical Biochemistry, Aalborg University Hospital, Denmark. Blood samples collected from 216 patients with known monoclonal gammopathy were analyzed on Alinity, Cobas and Optilite. Diagnoses were ascertained from clinical records. Scatter plots with Passing-Bablok regression were used to investigate associations between concentrations of IgA, IgG and IgM measured with each of the different instruments. Furthermore, comparison of IgG analyses on Alinity, Optilite and Cobas according to monoclonal IgM concentration was explored with Bland-Altman plots. A total of 81 patients were identified with IgM type monoclonal gammopathy and 8 of these patients (10%) had analytical interference as reflected by more than 25% decrease in the level of IgG measured on Alinity as compared to Optilite and Cobas. All blood samples with interference on IgG measurement using Alinity were from patients with lymphoplasmacytic lymphoma/Waldenströms macroglobulinemia and all of them had monoclonal IgM concentrations above 10 g/L. This study identified a source of interference from IgM monoclonal gammopathy on IgG measurement performed using Alinity. The interferences caused falsely low results of IgG which is important to recognize to ensure proper patient management.

Safety of Oral Food Challenges for Individuals with Low Levels of Cow's Milk-Specific Immunoglobulin E Antibodies.

Cow's milk (CM) is one of the most common food allergens in Japan. The oral food challenge (OFC) of CM is important for the definite diagnosis of children with CM allergy and it is recommended to be actively and safely performed in individuals with low CM-sIgE levels. This study aimed to investigate the safety of low-dose CM-OFC in individuals with low CM-sIgE levels and discuss the prognostic factors and appropriate approaches for assessing the starting doses of CM-OFC in these individuals. We retrospectively analyzed 6,929 OFC tests conducted between January 1, 2017 and December 31, 2021; of which, 1,390 were CM-OFC tests. The characteristics, OFC-positive rates, CM loading, and related factors were analyzed in 138 cases involving low CM-sIgE levels. Stepwise OFC tests were conducted according to the FA guidelines in Japan using an open and unblinded method. Among 138 individuals with low CM-sIgE levels, 110 (79.7%) passed the OFC test without any symptoms. Among the cases with OFC-positive status, 50.0% (14/28) cases showed symptoms with low-dose OFC (30-105 mg CM protein). Moreover, complete CM elimination was associated with a significantly high OFC-positive rate, and 60.0% (12/20) of the cases involving complete CM elimination showed symptoms with low-dose OFC. Eighty percent of the patients with low CM-sIgE levels safely completed the OFC test. Nevertheless, careful observation is essential during low-dose OFC test in cases with low CM-sIgE levels, especially in the cases with complete elimination. The starting dose of the OFC test should be re-evaluated and modified using baked milk or a lower dose of CM to ensure safety and early outgrowth of CM allergy.

Effect of acupuncture combined with bloodletting therapy on mast cell degranulation in urticaria rats

To observe the effects of acupuncture combined with bloodletting on the expression of inflammatory factors in serum, the morphology of sensitized skin tissue and the mast cell degranulation in urticaria rats, and to explore the potential mechanism of this therapy for urticaria. Among 42 SD rats of SPF grade, 6 rats were randomly collected for the preparation of sensitized antiserum; and the rest 36 rats were randomized into a blank group, a model group, a positive drug group, an acupuncture group, a bloodletting group and a combined treatment group (acupuncture + bloodletting), 6 rats in each one. The rat model of urticaria was established by passive cutaneous anaphylaxis. In the positive drug group, loratadine (1 mg•kg-1) by gavage was administered once a day. In the acupuncture group, 1 h after gavage with 0.9% NaCl (1 mL), acupuncture was delivered at "Baihui" (GV 20), "Zhongwan" (CV 12), and bilateral "Quchi" (LI 11) and "Xuehai" (SP 10) for 15 min, once daily . In the bloodletting group, 1 h after gavage with 0.9% NaCl (1 mL), bloodletting was operated at "Dazhui" (GV 14) and bilateral "Geshu" (BL 17), around 0.1 mL of bleeding volume at each point, once daily. In the combined treatment group, 1 h after gavage with 0.9% NaCl (1 mL), the interventions as the acupuncture group and the bloodletting group were adopted, once daily. All the interventions started on day 6 of modeling, lasting 2 weeks. After intervention completion, antigenic stimulation was performed in the rats of each group. Using ELISA, the levels of serum immunoglobulin E (IgE), tryptase (TPS), interleukin-4 (IL-4), interleukin-5 (IL-5), tumor necrosis factor-α (TNF-α) were detected. The diameter of the blue spots of the sensitized skin on the back was measured with ruler in each rat. The morphology of sensitized skin tissue was observed using HE staining, and the degranulation of mast cells was observed using Toluidine blue staining. Compared with the blank group, in the model group, the levels of serum IgE, TPS, IL-4, IL-5 and TNF-α increased (P<0.01), the diameter of blue spot on the sensitized part of the rat back was larger (P<0.01), the degranulation rate of mast cells was elevated (P<0.01), and there were obvious inflammatory cell infiltration and edema in the dermis of sensitized skin tissue on the rat back. Compared with the model group, the serum levels of IgE, TPS, IL-4, IL-5 and TNF-α were reduced in the positive drug group, the acupuncture group, the bloodletting group and the combined treatment group (P<0.01, P<0.05); skin blue spot diameter was smaller in the positive drug group and the combined treatment group (P<0.05); the degranulation rate of mast cells decreased in the positive drug group, the acupuncture group, the bloodletting group and the combined treatment group (P<0.01); and the dermal edema, inflammatory infiltration were attenuated in the positive drug group, the acupuncture group, the bloodletting group and the combined treatment group. Compared with the acupuncture group and the bloodletting group, the serum levels of IgE, TPS, IL-4, IL-5 and TNF-α, as well as the degranulation rate of mast cells in the sensitized tissue were lower in the positive drug group and the combined treatment group (P<0.05). Acupuncture combined with bloodletting effectively suppress mast cell degranulation in the sensitized skin tissue on the back of urticaria rats, and ameliorate the histopathological morphology. Its effect mechanism may be related to inhibiting the differentiation and proliferation of helper T cells 2 and regulating the humoral immune response.

The association of Helicobacter pylori with adverse pregnancy outcomes in three European birth cohorts

BackgroundHelicobacter pylori is a prevalent infection that may complicate pregnancy, but evidence remains limited, controversial and may not apply to all pregnant women.ObjectiveThis study aims to evaluate whether Helicobacter pylori is a risk factor for adverse pregnancy outcomes and to identify vulnerable subpopulations.Study designMultiplex serology was utilized to measure blood levels of immunoglobulin G against eight Helicobacter pylori antigens in 1372 pregnant women from three European birth cohorts: BiB (United Kingdom), Rhea (Greece) and INMA (Spain). Outcomes of interest included gestational diabetes mellitus, gestational hypertension, preeclampsia, preterm birth and small for gestational age neonates, as well as prenatal anxiety and depression. Adjusted logistic regression models were used to evaluate the association between Helicobacter pylori seropositivity (overall and by antigen) and antigen specific antibody levels with the outcomes. We examined effect modification of the associations by ethnicity.ResultsHelicobacter pylori seropositivity was detected in 18.8% (258/1372) of pregnant women. Preeclampsia was the least common outcome (26/830). Helicobacter pylori seropositivity was associated with the development of two or more adverse pregnancy outcomes (gestational hypertension, gestational diabetes, preterm birth, small gestational age and preeclampsia) [OR:1.32 (95% CI: 1.06–1.65), p-value: 0.01], especially in women with high antibody levels to OMP antigen [OR: 2.12 (95% CI: 1.62–2.76), p-value: 0.001]. Women with high antibody levels to Helicobacter pylori antigens GroEL and NapA were more likely to develop preeclampsia [OR: 2.34 (95% CI: 1.10–8.82), p-value: 0.03; OR: 4.09 (95% CI: 1.4-11.93), p-value 0.01)]. Helicobacter pylori seropositivity increased the odds of developing any hypertensive disorder during pregnancy among women of western ethnicity (948/1372) [OR:3.35 (95% CI: 1.29–8.74), p-value 0.03].ConclusionOur study suggests that Helicobacter pylori seropositivity is a risk factor for multiple adverse pregnancy outcomes and particularly in women of western origin for hypertensive disorders during pregnancy. Moreover, pathogen specific characteristics reflected in the antibody responses against OMP, GroEL and NapA seem to determine disease associations.