Total Serum IgG Research Articles

The effects of dietary supplementation with lotus leaf extract on the immune response and intestinal microbiota composition of broiler chickens

This study aimed to assess the effect of lotus leaf extract (LLE) on the immune response and intestinal microbiota composition of broiler chickens. One-day-old birds were assigned to 7 treatments. Two maize-based control diets were each given with or without 50 mg/kg chlortetracycline (antibiotics and blank control groups, respectively). Five experimental diets were each given with 1.0, 2.5, 5.0, 7.5, or 10.0 g/kg LLE. Average daily weight gain (ADG) was assessed, and the immune organ index was calculated. Serum cytokine and immunoglobulin levels were determined, and intestinal microbiota composition was analyzed via high-throughput sequencing of the 16S rRNA gene. Results showed that in the LLE5 group, ADG was higher than that of the antibiotics and blank control groups (P < 0.05) from d 7 to 21, the thymus index at d14, spleen index at d 21, and bursa index at d 14 and 21 were increased markedly (P < 0.05). In the LLE5 and LLE7.5 groups, serum total IgG and sIgA concentrations were higher than those of the antibiotics and blank control groups (P < 0.05) at d 7 and higher than those of the antibiotics group (P < 0.05) at d 14. No significant effect was observed for interferon-gamma concentrations between the antibiotics and LLE5 or LLE7.5 groups; compared with the antibiotics group, IL2 concentrations were increased in the LLE5 group at d 7 and in the LLE7.5 group at d 21 (P < 0.05). 16s rRNA sequencing analysis revealed that there were 1,704, 232, and 4,814 operational taxonomic unit in the blank control group, antibiotics group, and LLE groups, respectively. The intestinal microbiota consisted mainly of Firmicutes, Proteobacteria, Actinobacteria, and Bacteroidetes (>95%) at the phylum level; at the family level, the abundance of Clostridiaceae and Bacteroidales S24-7 was increased, whereas that of Peptostreptococcaceae was reduced in LLE5 group (P < 0.05). These findings suggest that LLE may be a good source of prebiotics, helping to modulate the immune response and boost the levels of beneficial bacteria.

Impact of asthma on bronchiectasis severity and risk of exacerbations

Objective Asthma is a frequent comorbidity of bronchiectasis, with possible implications for exacerbation and severity. We investigated the clinical impact of asthma on bronchiectasis in terms of disease severity and exacerbation risk. Methods We collected demographic, clinical, and functional characteristics of patients with a confirmed diagnosis of bronchiectasis. All patients were investigated for concomitant diagnosis of asthma. The Bhalla score was used to assess radiological severity of bronchiectasis, and the Bronchiectasis Severity Index (BSI) was used to assess the clinical severity. Blood and sputum samples were collected to assess blood cell count, erythrocyte sedimentation rate, c-reactive protein, immunological status (IgA, IgE, IgM, IgG, and IgG subclasses), and microbiological analysis. Results A total of 106 patients were enrolled in the study; 30.2% had concomitant asthma and were characterized by higher frequency of bronchiectasis exacerbation, despite higher Bhalla score and lower BSI compared to patients without asthma. Pseudomonas aeruginosa was more frequently isolated from the sputum of bronchiectasis patients without asthma. Total serum IgG, IgG1, and IgG3 were lower in patients with asthma. Blood eosinophils and exhaled nitric oxide were higher in patients with associated asthma. The presence of asthma and presence of Pseudomonas in sputum were the only significant determinants of frequent exacerbations in a binary logistic regression analysis. Conclusion The coexistence of asthma and bronchiectasis is associated with an independent increase in the risk of bronchiectasis exacerbation despite lower radiological and clinical severity indexes. Asthmatic airway inflammation could promote an enhanced “Cole’s Cycle” that is responsible for a higher frequency of exacerbations.

Hypertrophic pachymeningitis, IgG4-related disease: case report

ABSTRACT The IgG4-related disease (IgG4-RD) is a systemic disease recently characterized as an inflammatory condition generally related to the increase in serum IgG4 levels, a subclass of immunoglobulins (IgG) which corresponds to less than 6% of the total serum IgG, with singular histopathological features. The involvement of the central nervous system is rare and may be isolated or associated with other organs, mimicking tumors. Commonly, it involves the hypophysis, presenting hypophysitis as the main manifestation, but it can also affect the dura mater, presenting as IgG4-related hypertrophic pachymeningitis (IgG4-RHP). Neurological manifestations occur as a result of mass effect, typically due to vascular or nervous structures compression, resulting in functional deficits according to the anatomical site of the lesion. The main histopathological features are dense lymphoplasmacytic infiltrate, fibrosis arranged, at least focally, in a storiform pattern, and obliterative phlebitis, associated with increased numbers of IgG4+ plasma cells or an increased IgG4/IgG ratio in tissue. In this disease, the serum IgG4 levels are usually increased. The objective of this article is to report the case of a 37-year-old male patient who presented a pulsatile headache associated with diplopia and blurred vision. After radiological, histopathological and immunohistochemical studies, the diagnosis of IgG4-RHP was confirmed, besides presenting a literature review about IgG4-RD and IgG4-RHP.

The effect of various heat-treatment methods on colostrum quality, health and performance of dairy calves

To investigate the effect of feeding heat-treated colostrum at different duration on the health and performance, 48 Holstein calves were enrolled randomly into four treatment groups before first feeding and consumed untreated colostrum (H0, n = 12), heat-treated colostrum at 60ºC for 30 min. (H30, n = 12), heat-treated colostrum at 60ºC for 60 min. (H60, n = 12) and heat-treated colostrum at 60ºC for 90 min. (H90, n = 12). Blood samples were collected for analyses of IgG and protein profile at 0, 6, and 24h of age. The colostrum sample from treated and untreated batches and feces sample from each calf also were taken. The results showed heat-treatment of colostrum at 60ºC for 60 (p = 0.03) and 90 min. (p = 0.01) reduced total bacterial count, while colostral IgG concentration maintained up to 60 min. Serum total protein (p = 0.02), IgG concentrations (p = 0.03), and apparent efficiency of IgG absorption (p = 0.02) were significantly greater at 6 and 24h in calves that were fed heat-treated colostrum (H90) compared to calves fed unheated colostrum (H0). General health status of calves that were received heat-treated colostrum was better and the prevalence of diarrhea-induced pathogens was lower than calves were fed unheated colostrum. In conclusion, the consumption of heat-treated colostrum had a positive effect on health, growth characteristics, and performance of calves during the suckling period.

The effect of various heat-treatment methods on colostrum quality, health and performance of dairy calves

ABSTRACT. To investigate the effect of feeding heat-treated colostrum at different duration on the health and performance, 48 Holstein calves were enrolled randomly into four treatment groups before first feeding and consumed untreated colostrum (H0, n = 12), heat-treated colostrum at 60oC for 30 min. (H30, n = 12), heat-treated colostrum at 60oC for 60 min. (H60, n = 12) and heat-treated colostrum at 60oC for 90 min. (H90, n = 12). Blood samples were collected for analyses of IgG and protein profile at 0, 6, and 24h of age. The colostrum sample from treated and untreated batches and feces sample from each calf also were taken. The results showed heat-treatment of colostrum at 60oC for 60 (p = 0.03) and 90 min. (p = 0.01) reduced total bacterial count, while colostral IgG concentration maintained up to 60 min. Serum total protein (p = 0.02), IgG concentrations (p = 0.03), and apparent efficiency of IgG absorption (p = 0.02) were significantly greater at 6 and 24h in calves that were fed heat-treated colostrum (H90) compared to calves fed unheated colostrum (H0). General health status of calves that were received heat-treated colostrum was better and the prevalence of diarrhea-induced pathogens was lower than calves were fed unheated colostrum. In conclusion, the consumption of heat-treated colostrum had a positive effect on health, growth characteristics, and performance of calves during the suckling period.

Identification of biomarkers measured upon arrival associated with morbidity, mortality, and average daily gain in grain-fed veal calves

There is a strong need for management strategies that help reduce the incidence of disease and subsequent antimicrobial use in the veal industry. Biomarkers could serve as useful tools that allow producers to take preventative measures before clinical problems occur. The objective of this prospective cohort study was to identify biomarkers measured upon arrival associated with morbidity, mortality, and average daily gain (ADG) in grain-fed veal calves. Upon arrival at a grain-fed veal facility in Ontario, Canada, calves were weighed and health-scored using a standardized health-scoring system. Several metabolites were measured including creatine kinase (CK), cholesterol, haptoglobin, manganese, serum total protein, iron, cobalt, zinc, selenium, molybdenum, and IgG. Farm personnel treated calves according to their farm protocol and weighed them at 78 d after arrival. Performance, treatment, and mortality records from the facility were used for analysis. Multivariable Cox proportional hazard models were created to evaluate metabolic biomarkers associated with morbidity and mortality. A mixed linear regression model was created to determine biomarkers associated with ADG. A total of 992 male dairy calves were evaluated at arrival from January to December 2017. Of the calves evaluated, 74 calves (7.5%) died and 877 (88.4%) were treated for illness over the 11-wk period under observation. Higher levels of haptoglobin and molybdenum were associated with a greater hazard of morbidity, whereas higher weight upon arrival and higher levels of both CK and IgG were associated with a reduced hazard of morbidity. For mortality, higher weight upon arrival and higher levels of cholesterol and IgG were associated with a lower hazard of mortality occurring over the 78-d period of observation. Higher weight, cholesterol, copper, CK, iron, and IgG were associated with increased ADG, whereas increased zinc and haptoglobin were negatively associated with ADG. These results demonstrate that certain biomarkers could be used to identify high-risk calves when measured upon arrival at a veal facility. Future research should focus on determining the utility of these biomarkers to selectively target intervention strategies to improve ADG and reduce morbidity and mortality.

B7-H4 Inhibits the Development of Primary Sjögren's Syndrome by Regulating Treg Differentiation in NOD/Ltj Mice.

Background This study is aimed at exploring the role of B7-H4 in the pathogenesis of primary Sjögren's syndrome (pSS) in NOD/Ltj mouse. Methods B7-H4 expression in salivary glands was examined by IHC, and lymphocyte infiltration was showed by H&E. Next, anti-B7-H4 mAb or immunoglobulin isotype was injected into NOD/Ltj mice. Cytokine levels were measured by quantitative RT-PCR, and immunoglobulins were measured by ELISA. T cell subsets were analyzed by flow cytometry. Last, we treated NOD/Ltj mice with B7-H4Ig and control Ig. CD4+Foxp3+ T cells were assessed by immunohistochemistry. Two-tailed Student's t-tests were used to detect the statistical difference in various measures between the two groups. Results B7-H4 expression was remarkably reduced in salivary glands of NOD/Ltj mice at 15 weeks compared with the NOD/Ltj mice at 8 weeks. Anti-B7-H4 mAb treatment increased lymphocyte infiltration in salivary glands. Inflammatory cytokines including IL-12, IL-18, IL-1α, TNF-α, IFN-α, and BAFF were upregulated markedly in anti-B7-H4 mAb-treated mice compared to IgG isotype-treated mice. Flow cytometry analysis showed that anti-B7-H4 mAb-treated mice had lower levels of CD4+Foxp3+/CD4+ T cells in spleen. Moreover, Foxp3 mRNA levels of salivary glands were diminished in anti-B7-H4 mAb-treated mice. Flow cytometry analysis showed that anti-B7-H4 mAb inhibited CD4+Foxp3+/CD4+ T cell production, while B7-H4Ig would promote naïve CD4+ T into Treg differentiation. Administration with B7-H4Ig displayed significantly decreased lymphocyte infiltration in salivary glands and low levels of total IgM and IgG in serum. Analysis of inflammatory cytokines in salivary glands after B7-H4Ig treatment revealed that the mRNA levels of IL-12, IL-6, IL-18, IL-1α, TNF-α, and IFN-α were significantly downregulated in B7-H4Ig-treated mice compared to control Ig treatment. B7-H4Ig-treated mice had significantly higher levels of CD4+Foxp3+/CD4+ T cells in spleen. IHC in salivary gland revealed that CD4+Foxp3+ T cells of B7-H4Ig treatment mouse were more than control Ig treatment. Conclusions Our findings implicate that B7-H4 has a protective role for salivary gland epithelial cells (SGECs) and therapeutic potential in the treatment of pSS.

The Oxidative Stress Mediated Toxicity and Immunotoxic Effect of Copper Oxide Nanoparticles on Spleen of Adult Albino Rats

The escalated use of copper oxide nanoparticles (CuO NPs) in various fields increased risk of human and environmental exposure. Spleen accounts for a crucial role in both innate and adaptive immunity and represents a potential target for nanoparticles toxicity. The aim of this study was to investigate the immunotoxic effect of sub-acute oral exposure to CuO NPs on spleen of adult male albino rats. Thirty rats were divided into two main groups. Group (I) control which was subdivided into two groups (10 rats each): (IA) negative control and (IB) positive control (received deionized water). Group II received CuO NPs (125 mg/kg). Animals were orally gavaged with treatments on a daily base for 28 days. At the end of experiment, blood samples were used to assess number of red blood corpuscles (RBCs), hemoglobin (Hb%), platelets (PLT), white blood cells count (WBCs), and differential leucocyte count (neutrophils, monocytes, and lymphocytes). Serum samples were analyzed for total IgG and IgM levels. Thereafter, spleens were resected to assess levels of malondialdehyde (MDA), superoxide dismutase (SOD), tumor necrosis factor-alpha (TNF- α), and interleukin-4 (IL-4). Number of T-Lymphocyte subpopulation (CD4+, CD8+ and CD19+) and histopathology (H&E) were also determined. Results of the present study revealed that CuO NPs significantly decreased RBCs, Hb%, PLT, WBCs and lymphocytes% and significantly increased neutrophils% and monocytes%. Also, a significant reduction in total IgG and IgM in serum was detected. Furthermore, spleens of CuO NPs treated group demonstrated significant elevation in MDA, TNF- α., and CD8+. Meanwhile, SOD, IL4, CD4+, CD19+ and CD4+ /CD8+ ratio were significantly decreased. Structural damage was indicated by reduced number and cellularity of lymphoid follicles, as well as, congestion of red pulps. It can be concluded that the immune function of spleen was intoxicated by CuO NPs mostly due to oxidative stress mechanism and inflammation.

Significance of Anti-Nuclear Antibodies and Cryoglobulins in Patients with Acute and Chronic HEV Infection.

Background: Hepatitis E virus (HEV) has been associated with immunological phenomena. Their clinical significance, however, still needs to be clarified, that is, whether cryoglobulins or autoantibodies impact overt disease in HEV-infected individuals. To better understand, we analyzed these different immune phenomena in three cohorts, each representing different types of HEV infection. Methods: The cohorts included: (i) immunocompetent patients with acute hepatitis E, (ii) immunosuppressed patients with chronic hepatitis E, and (iii) individuals with asymptomatic HEV infection. Together, they consisted of 57 individuals and were studied retrospectively for the presence of anti-nuclear antibodies (ANAs), cryoglobulins, and serum total IgG. They were then compared with a control cohort of 17 untreated patients with chronic hepatitis B virus (HBV) infection or hepatitis C virus (HCV) infection. Results: Thirteen (23%) were immunocompetent patients with acute hepatitis E (median alanine aminotransferase (ALT) = 872 U/L), 15 (26%) were immunosuppressed patients with chronic hepatitis E (median ALT = 137 U/L), and 29 (51%) were blood donors with asymptomatic HEV infection (median ALT = 35 U/L). Overall, 24% tested positive for elevated ANA titers of >1:160, and 11% presented with a specific ANA pattern. ANA detection was not associated with the type of HEV infection, IgG levels, sex, or age. All individuals tested negative for anti-mitochondrial antibodies, anti-neutrophil cytoplasmic antibodies, liver-kidney microsomal antibodies, anti-myeloperoxidase-, and anti-proteinase-3 antibodies. Five patients (9%) tested positive for cryoglobulins. Notably, cryoglobulinemia was present in overt hepatitis E (Groups (i) and (ii); one acute and four chronic HEV infections), but was not present in any of the asymptomatic blood donors (p = 0.02). The frequency of cryoglobulins and elevated ANAs did not differ significantly between HEV and HBV/HCV patients. Conclusion: In line with findings on HBV and HCV infections, we frequently observed detection of ANAs (24%) and cryoglobulins (9%) in association with HEV infections. The presence of cryoglobulins was limited to patients with overt hepatitis E. We add to the findings on the immune phenomena of hepatitis E.

Kinetics of IgG Antibodies in Previous Cases of Dengue Fever-A Longitudinal Serological Survey.

Guangzhou is believed to be the most important epicenter of dengue outbreaks in southern China. In this study, a longitudinal serological investigation of previous cases of dengue fever in Guangzhou was conducted to explore the persistence of IgG antibodies and related factors affecting the changes of antibody level. We recruited 70 dengue virus type 1 (DENV-1) primary infection cases at two years post infection for serological investigation and conducted a second follow-up in the 5th year of prognosis. An enzyme-linked immunosorbent assay (ELISA) for DENV IgG antibody was examined in all study subjects. Potential factors associated with the concentration of serum total IgG antibody were determined by the generalized estimation equation (GEE). No significant difference in serum total IgG antibody positive rate between two follow-ups was observed (χ2 = 3.066, p = 0.080). However, there was a significant difference in the concentration of serum total IgG antibody between the two follow-ups (Z = 7.154, p < 0.001). The GEE showed that the antibody level in the five-year prognosis was mainly affected by the antibody level in the two-year prognosis (OR: 1.007, 95%CI: 1.005–1.009). In conclusion, the serum IgG antibodies of previous dengue fever cases can persist for a long time.

Plasma C3d levels as a diagnostic marker for complete complement factor I deficiency

Plasma C3d levels as a diagnostic marker for complete complement factor I deficiency

Protective effect of fungal extracellular vesicles against murine candidiasis.

Extracellular vesicles (EVs) are lipid bilayered compartments released by virtually all living cells, including fungi. Among the diverse molecules carried by fungal EVs, a number of immunogens, virulence factors and regulators have been characterised. Within EVs, these components could potentially impact disease outcomes by interacting with the host. From this perspective, we previously demonstrated that EVs from Candida albicans could be taken up by and activate macrophages and dendritic cells to produce cytokines and express costimulatory molecules. Moreover, pre-treatment of Galleria mellonella larvae with fungal EVs protected the insects against a subsequent lethal infection with C. albicans yeasts. These data indicate that C. albicans EVs are multi-antigenic compartments that activate the innate immune system and could be exploited as vaccine formulations. Here, we investigated whether immunisation with C. albicans EVs induces a protective effect against murine candidiasis in immunosuppressed mice. Total and fungal antigen-specific serum IgG antibodies increased by 21 days after immunisation, confirming the efficacy of the protocol. Vaccination decreased fungal burden in the liver, spleen and kidney of mice challenged with C. albicans. Splenic levels of cytokines indicated a lower inflammatory response in mice immunised with EVs when compared with EVs + Freund's adjuvant (ADJ). Higher levels of IL-12p70, TNFα and IFNγ were detected in mice vaccinated with EVs + ADJ, while IL-12p70, TGFβ, IL-4 and IL-10 were increased when no adjuvants were added. Full protection of lethally challenged mice was observed when EVs were administered, regardless the presence of adjuvant. Physical properties of the EVs were also investigated and EVs produced by C. albicans were relatively stable after storage at 4, -20 or -80°C, keeping their ability to activate dendritic cells and to protect G. mellonella against a lethal candidiasis. Our data suggest that fungal EVs could be a safe source of antigens to be exploited in vaccine formulations.

Neonatal infection and passive acquisition of serum total IgG and reactive with "Streptococcus" B, anti-LPS of "Klebsiella spp" and "Pseudomonas spp" antibodies in twins.

OBJECTIVE To describe the concentration of total and specific IgG antibodies anti-Streptococcus B, anti-lipopolysaccharide of Klebsiella spp, and anti-lipopolysaccharide of Pseudomonas spp in the umbilical cord of newborn(NB) twins and to analyze the association between neonatal infection and antibody concentration in the umbilical cord blood. METHODS A prospective cross-sectional study of a cohort of NB twins admitted during the period of 20 months. Patients with malformations and mothers with infection were excluded. Variables analyzed: gestational age(GA); birth weight(BW); antibody concentrations in umbilical cord blood; infection episodes. We used the paired Student t-test, Spearman correlation, and generalized estimation equation. RESULTS 57 pairs of twins were included, 4 excluded, making the sample of 110 newborns. GA=36±1.65weeks and BW=2304.8±460g(mean±SD). Antibody concentrations in twins(mean±SD): total IgG=835.71±190.73mg/dL, anti-StreptococcusB IgG=250.66±295.1 AU/mL, anti-lipopolysaccharide of Pseudomonas spp IgG=280.04±498.66 AU/mL and anti-lipopolysaccharide of Klebsiella spp IgG=504.75±933.93 AU/mL. There was a positive correlation between maternal antibody levels and those observed in newborns(p <0.005). The transplacental transfer of maternal total IgG and anti-LPS Pseudomonas IgG antibodies was significantly lower at NB GA <34 weeks(p <0.05). Five newborns were diagnosed with an infection. Infants with infection had significantly lower total IgG concentration(p <0.05). CONCLUSION This study showed a positive correlation between maternal and newborn antibodies levels. In infants younger than 34 weeks there is less transfer of total IgG and anti-LPS Pseudomonas IgG. The highest incidence of infection in the newborn group who had significantly lower total IgG serum antibodies reinforces the importance of anti-infectious protection afforded by passive immunity transferred from the mother.

IL-10-producing B cells play important role in the pathogenesis of recurrent pregnancy loss

Interleukin (IL)-10-producing B cells are recently known for their regulatory function in several disorders. However, the possible role of these cells remains unclear in recurrent pregnancy loss (RPL) pathogenesis. Total B cells from 24 RPL patients with cellular immune abnormalities, as well as that of 25 normal pregnant women were cultured and stimulated by Toll Like Receptor (TLR) agonists (CpG oligodeoxynucleotides (ODN) and imiquimod). Then, the frequency of IL-10+ CD19+ B cells was found out using flow cytometry. Enzyme-linked immunosorbent assay (ELISA) was used to assess the levels of IL-10 in supernatant medium and serum of stimulated B cells, as well as those of several serum autoantibodies. Real-Time PCR method was carried out for determining the IL-10 expression level and specific genes transcripts. RPL patients indicated a lower proportion of IL-10+ CD19+ B cells, and reduced levels of IL-10 in both serum and supernatant of the culture medium of the stimulated B cells. According to the results, total IgG levels was greater in serum of RPL patients in comparison with healthy pregnant women. Similarly, the percentage of these cells was negatively correlated with serum total IgG levels and the number of miscarriages. The expression levels of the mRNA of programmed death-ligand 1 (PD-L1) and IL-10 were lower in RPL patients, while those of x binding protein 1 (XBP-1), interferon regulatory factor 4 (IRF4), and B lymphocyte-induced maturation protein 1 (BLIMP1) were significantly increased. These observations indicated that the reduction in the population of peripheral blood IL-10-synthesizing B cells may prompt RPL pathogenesis, suggesting suppressive effects of these cells on autoantibody production and successful pregnancy outcomes.

Effect of Dietary Vitamin D3 on T Helper-Related Activities of Lupus-Prompt New Zealand Black/New Zealand White F1 Mice

We investigated the effect of dietary vitamin D3 on T helper-related activities and progress of lupus in NZB/NZW F1 mice. Mice were fed with 0.4 or 2 μg vitamin D3 dissolved in 50 μL olive oil every other day. Expression of T cell-related cytokine genes including those of IL-2, IL-4, IL-5, IL-6, IL-10, IL-12 and IFN-γ was monitored during the disease course by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). In addition, total serum IgG1 and IgG2a and anti-dsDNA antibody were measured. We observed a prolonged survival of mice receiving 2μg of vitamin D3 as compared with control mice. However, vitamin D3 did not significantly affect the anti-DNA antibody formation, IgG subtype proportion, or cytokine expression profile.

Development and evaluation of a new recombinant protein vaccine (YidR) against Klebsiella pneumoniae infection

Vaccination is a promising approach to prevent Klebsiella infection; however, the high heterogeneity of strains is a limiting factor. The best antigenic target for an anti-Klebsiella vaccine should be expressed by all or most of strains. We previously found YidR protein to be highly conserved among K. pneumoniae strains independently of antigen serotype. Therefore, in the present study, we developed a recombinant YidR protein vaccine and evaluated its protective efficacy against lethal challenge with K. pneumoniae in a mouse model. The yidR gene was cloned in Escherichia coli for recombinant expression. The lethal dose (LD100) of K. pneumoniae was determined and lethal challenge was carried out after immunization with recombinant purified YidR. After immunization, the concentration of total serum IgG was significantly higher in YidR-immunized mice than in non-immunized mice, indicating strong induction of antibodies. Mice were challenged with LD100 of K. pneumoniae, and significantly lower murine sepsis and higher body weight were observed in YidR-immunized mice compared to unvaccinated controls. Moreover, ∼90% of YidR-immunized mice survived beyond 10 days of observation, whereas none of the control mice survived past 48 h. The protective effect of YidR recombinant protein vaccine was demonstrated and YidR may be a promising vaccine candidate to prevent klebsiellosis.

Immunoglobulin G Subclass-Specific Glycosylation Changes in Primary Epithelial Ovarian Cancer.

Epithelial ovarian cancer (EOC) was previously shown to be associated with glycosylation changes of total serum and total IgG proteins. However, as a majority of previous studies analyzed released glycan profiles, still little is known about IgG subclass-specific alterations in ovarian cancer. Hence, in this study, we investigated EOC-related glycosylation changes of the three most abundant IgG subclasses, namely, IgG1, IgG2 and IgG3 isolated from sera of 87 EOC patients and 74 age-matched healthy controls. In order to separate IgG2 and IgG3, we performed a two-step affinity purification employing Protein A and Protein G Sepharose. After tryptic digestion, IgG glycopeptides were enriched and measured by MALDI-TOF-MS. Finally, EOC-related glycosylation changes were monitored at the level of total agalactosylation, monogalactosylation, digalactosylation, sialylation, bisection and fucosylation, which were calculated separately for each IgG subclass. Interestingly, aside from an EOC-related increase in agalactosylation/decrease in monogalactosylation and digalactosylation observed in all IgG subclasses, some subclass-specific trends were detected. Glycosylation of IgG1 was found to be most strongly affected in EOC, as it exhibited the highest number of significant differences between healthy controls and EOC patients. Specifically, IgG1 was the only subclass that showed a significant decrease in sialylation and a significant increase in fucosylation in EOC patients. Interestingly, IgG2 and IgG3 that were often investigated collectively in previous studies, were found to have distinct glycosylation patterns. IgG3 displayed stronger EOC-related increase in agalactosylation/decrease in digalactosylation and was characterized by notably higher sialylation, which consequently decreased in EOC patients. In conclusion, our study indicates that IgG subclasses exhibit subtly distinct glycosylation patterns of EOC-related alterations and that IgG1 and IgG3 agalactosylation show the strongest association with CA125, the routine diagnostic marker. Additionally, our results show that simultaneous analyses of IgG2 and IgG3 might lead to wrong conclusions as these two subclasses exhibit noticeably different glycosylation phenotypes.

Clinical and immunological features of 44 common variable immunodeficiency patients: the experience of a single center in Turkey

Introduction and objectivesCommon variable immunodeficiency (CVID) is one of the most prevalent forms of primary immunodeficiency characterized by hypogammaglobinemia. Its heterogeneous clinical features include recurrent respiratory tract infections and other complications such as gastrointestinal, autoimmunity, and lymphoproliferative disorders. The aim of this article is to evaluate the general characteristics of CVID patients. Materials and methodsClinical and immunological features of 44 CVID patients were evaluated retrospectively with long-term follow-up. Patients who participated in the study were diagnosed according to the criteria of the European Society for Immunodeficiency Diseases (ESID). ResultsThe median age at onset of symptoms was 2.75 years (range 6 months to 17 years), and the median age at diagnosis was 7.75 years (range 4–20 years). The average delay in diagnosis was 4.6 years (range 1–14 years). Positive family history was 18.2%. Before treatment, patients’ median total serum IgG was 271.5mg/dL, median IgA was 7.5mg/dL, and median IgM was 21mg/dL. Infections were the most common clinical manifestation, and 63.6% of patients presented with sinopulmonary infection as the first manifestation. Bronchiectasis developed in 23 CVID subjects, while bronchiectasis was detected prior to CVID diagnosis in eight patients. All patients received immunoglobulin replacement therapy, and one patient died because of granulomatous lymphocytic interstitial lung disease (GLILD). ConclusionsCVID is a heterogeneous group of immunologic disorders with unknown etiology. There are significant differences in the clinical presentation and prevalence of CVID-related complications among countries. Local guidelines for diagnosis and clinical follow-up are needed.

Comparison of immunoglobulin G absorption in calves fed maternal colostrum, a commercial whey-based colostrum replacer, or supplemented maternal colostrum

Successful passive transfer of antibodies in neonatal calves can be achieved by feeding an adequate quantity and quality of maternal colostrum (MC) or colostrum replacer (CR). An alternative could be feeding low-quality maternal colostrum (LMC) with added IgG from a CR. The objective of this study was to determine if a commercial whey-based CR product containing low levels of casein (Premolac PLUS Bovine IgG; Zinpro Corporation, Eden Prairie, MN) fed to replace MC or supplement LMC could lead to adequate serum IgG levels and apparent efficiency of absorption (AEA) in neonatal dairy calves. Holstein calves (n = 20 per treatment) were separated from their dam after birth and randomly assigned to be fed 3.79 L of MC (106 g/L of IgG; 401 g of IgG fed), LMC (30 g/L IgG) supplemented with CR (41 g/L IgG; 154 g of IgG total fed; LMC-CR), or 1.3 L of 1 of 2 levels of CR (110 or 150 g of IgG fed; CR-110 or CR-150) within 1.5 h of birth. Colostrum was obtained from the first (MC) or second and third milkings (LMC) of cows from Pennsylvania State University dairy and pooled by source into large batches. Blood samples were taken from calves before colostrum feeding and 24 h after birth and were analyzed for serum total protein, total IgG, hematocrit, and Brix percentage. Calves fed MC had higher 24-h IgG values (means ± SEM) than calves fed LMC-CR (27.04 ± 1.07 vs. 22.33 ± 1.08 mg/mL, respectively). Feeding 150 g of IgG from CR led to higher 24-h serum IgG values than feeding 110 g of IgG (16.90 ± 1.09 vs. 12.79 ± 1.08 mg/mL). Serum IgG levels were different between the CR-fed calves and the calves fed LMC-CR and MC, but all had average values >10 mg/mL IgG. Calves fed LMC-CR had greater AEA than calves fed MC (54.58 ± 2.39 vs. 24.38 ± 2.36%, respectively). Among calves fed CR-110 or CR-150, AEA did not differ. Serum total protein and Brix percentage had strong correlations with actual IgG values across the entire study. We found no differences in average daily gain or health variables measured, and no differences in final hip width, withers height, or body weight for calves fed MC, LMC-CR, CR-150, or CR-110. These results indicate that CR can be fed successfully as an alternative to MC or as a supplement to colostrum with low IgG.

Mixed polysaccharides derived from Shiitake mushroom, Poriacocos, Ginger, and Tangerine peel enhanced protective immune responses in mice induced by inactivated influenza vaccine

Influenza viruses are responsible for severe respiratory tract infections of individuals and may cause pandemics with a high risk of mortality and morbidity. Although vaccination is a primary means for prevention of influenza virus infections, poor vaccine performance or inadequate immune responses limits the efficacy of current vaccines and raises question regarding whether a better correlates of protection procedures should be performed. Here, we want to evaluate whether mixed polysaccharides (MPs) derived from shiitake mushroom, poriacocos, ginger, and dried tangerine peel could promote the immune response of inactivated influenza vaccine. Firstly, MPs were given to mice each day and for a total of 30 days, during which two immunizations were performed on mice on days 14 and 21. The results showed that serum total IgG and IgG2a levels were increased in MPs-treated mice on day 30. Following A/WSN/33 (H1N1) virus challenge, we found that MPs pretreatment in mice could increase mice weight gain and attenuate their clinical symptoms. Additional protective factors were also observed including prevention of excessive lung inflammation, promotion of CD19+ and CD278+ cell proportions in lung, elimination of virus in lung, and elevation of IFN-γ levels in serum. The current study demonstrate that MPs from shiitake mushroom, poriacocos, ginger, and dried tangerine peel could promote the immune efficacy and alleviate lung inflammation in mice with vaccines against H1N1 virus infection by activating both humoral and cellular immunity.