Immune Globulin G Research Articles

Changes in the N-glycosylation of porcine immune globulin G during postnatal development.

N-glycosylation influences the effectiveness of immune globulin G (IgG) and thus the immunological downstream responses of immune cells. This impact arises from the presence of N-glycans within the Fc region, which not only alters the conformation of IgG but also influences its steric hindrance. Consequently, these modifications affect the interaction between IgG and its binding partners within the immune system. Moreover, this posttranslational modification vary according to the physiological condition of each individual. In this study, we examined the N-glycosylation of IgG in pigs from birth to five months of age. Our analysis identified a total of 48 distinct N-glycan structures. Remarkably, we observed defined changes in the composition of these N-glycans during postnatal development. The presence of agalactosylated and sialylated structures increases in relation to the number of N-glycans terminated by galactose residues during the first months of life. This shift may indicate a transition from passively transferred antibodies from the colostrum of the sow to the active production of endogenous IgG by the pig's own immune system.

Effects and Mechanisms of Cage versus Floor Rearing System on Goose Growth Performance and Immune Status.

Currently, FRS and CRS are the two predominant dryland rearing systems in the goose industry. However, the effects of these two systems on goose growth performance and health, as well as the underlying mechanisms, have not been fully clarified. Thus, this study aimed to compare growth performance and immune status, as well as investigate the genome-wide transcriptomic profiles of spleen in geese, between CRS and FRS at 270 d of age. Phenotypically, the body weight and body size traits were higher in geese under FRS, while the weight and organ index of spleen were higher in geese under CRS (p < 0.05). Noticeably, the bursa of Fabricius of geese under FRS was degenerated, while that under CRS was retained. At the serum level, the immune globulin-G (IgG) and interleukin-6 (IL-6) levels were higher in geese under CRS (p < 0.05). At the transcriptomic level, we identified 251 differentially expressed genes (DEGs) in the spleen between CRS and FRS, which were mainly enriched in scavenger receptor activity, inflammatory response, immune response, neuroactive ligand-receptor interaction, phenylalanine metabolism, ECM receptor interaction, calcium signaling pathway, phenylalanine, tyrosine, and tryptophan biosynthesis, regulation of actin cytoskeleton, and MAPK signaling pathways. Furthermore, through protein-protein interaction (PPI) network analysis, ten candidate genes were identified, namely, VEGFA, FGF2, NGF, GPC1, NKX2-5, FGFR1, FGF1, MEIS1, CD36, and PAH. Further analysis demonstrated that geese in CRS could improve their immune ability through the "phenylalanine metabolism" pathway. Our results revealed that the FRS improved growth performance, whereas the CRS improved goose immune function by increasing levels of IL-6 and IgG in serum. Moreover, the phenylalanine metabolism pathway could exert positive effects on immune function of geese under CRS. These results can provide reliable references for understanding how floor and cage rearing systems affect goose growth performance and immune capacity.

Melatonin reduced colon inflammation but had no effect on energy metabolism in ageing Mongolian gerbils (Meriones unguiculatus)

In photoperiod-sensitive wild animals, the secretion of melatonin (MT) is modulated by external photoperiod, and MT affects inflammation and the ageing process. The beneficial effects of MT in delaying the progress of ageing have been reported in laboratory mice and rats. However, little is known about MT in wild mammals. In the current study, we investigated energy metabolism, microbial community structure and colon homeostasis in ageing Mongolian gerbils (Meriones unguiculatus) through exogenous supplementation of MT to test the hypothesis that MT has beneficial effects on gut homeostasis in ageing gerbils. Exogenous MT supplementation had no effect on energy metabolism in Mongolian gerbils but reduced the levels of circulating tumor necrosis factor-α (TNF-α), immune globulin G (IgG) and corticosterone (CORT). The increase in the level of inflammation in ageing animals was related to changes in the structure and diversity of the gut microbiota. At the genus level, the relative abundance of Prevotella, Treponema, Corynebacterium, and Sphingomonas was increased in ageing animals and decreased significantly by the treatment of MT. Christensenella and Lactobacillus were attenuated in ageing animals, and tended to be enhanced by MT treatment. Functions related to glycosphingolipid biosynthesis-ganglio series and lipopolysaccharide biosynthesis (metabolisms of cofactors, vitamins and glycan) were increased in ageing animals and decreased significantly by the treatment of MT. Our data suggest that a supplement of MT could improve colon homeostasis through changing the composition of gut microbiota and reducing inflammation in ageing gerbils.

2115. Long Term Follow-up and Correlates of Success in Patients on Immune Globulin for Antibody Deficiency

Abstract Background Antibody deficiencies range from mild deficits of antibody subclasses to more severe deficiencies of all immune globulins. Patients with deficiencies of immune globulin G (IgG) are predisposed to recurrent sinopulmonary infections, often necessitating multiple courses of antibiotics and frequent hospitalizations and provider visits. Treatment with intravenous immune globulin (IVIG) replacement therapy is currently indicated for patients with severe primary immune deficiencies but is less well studied in patients with more mild deficits that nonetheless experience recurrent infections. Methods A retrospective chart review was conducted on 71 patients from the Temple University Infectious Disease Department (15 transplant recipients) with varying levels of antibody deficiency that had been treated with monthly IVIG for at least six months. Available patients (N=49) were interviewed by phone about their experiences on IVIG, side effects, and quality of life changes on therapy. Results Mean age sx onset was 40 y,68% were women, 87% Caucasian, 49% had pneumonia, 65% purulent bronchitis, 65% sinusitis. Patients reported a mean reduction in infection frequency of 78% and average patient-reported improvement in quality of life was 4.7/5.0. Antibody deficiency levels at baseline were not correlated with infection reduction (R=-.05, p=0.71), Figure 1 and neither was response to pneumococcal polysaccharide vaccine (vaccine responder median infection reduction 83%; non responder 87%, p= 0.60) Figure 2. Adverse events on treatment were experienced by 59% of patients and caused 9 patients (13%) to stop treatment. There was no difference in incidence of adverse events between men and women (p= 0.076), but women had a 50% higher rates of severe headache than men (p= 0.038); 10% pts required a port or PICC, 32% IV fluids, 48% IV steroids, 31% IVIG brand change; 17% changed to subcutaneous IG. Figure 1:Pre-treatment Antibody Deficit and Infection Reduction by IVIGPlot of percent deficit of most deficient antibody subclass against infection reduction by IVIG (% of yearly pre-IVIG infections)Infection Reduction by IVIG According to Vaccine Responsiveness Box plot of percent infection reduction after IVIG according to response to polysaccharide vaccine Conclusion Even patients with relatively mild immunoglobulin deficiencies can experience a significant reduction in recurrent infections and improved quality of life when treated with immunoglobulin. IVIG is usually well tolerated for many years but may require adjunctive steroids, IV hydration, or brand change to limit adverse side effects. Disclosures All Authors: No reported disclosures.

Multiple myeloma diagnosed due to development of amyloid arthritis

Here, we present the case of a 72-year-old male who presented with swelling, stiffness, and dysesthesia in the bilateral fingers, wrists, and ankles. Although rheumatoid arthritis was initially suspected, laboratory tests were negative for rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) antibody. Based on the findings of immune globulin G (IgG)-λ M proteins and 26% plasma cells in the bone marrow, multiple myeloma was diagnosed. Joint sonography revealed thickening of the tendon synovial sheaths around the bilateral wrist joints, palmar flexor tendon sheaths, and extensor digitorum tendon sheaths, and magnetic resonance imaging (MRI) revealed soft tissue masses around the bilateral hip joints. Carpal tunnel syndrome associated with amyloid arthritis was suspected. Amyloid deposits were observed in synovectomy specimens, and the patient was then diagnosed with amyloid arthritis. He had concurrent pulmonary fibrosis, and treatment with lenalidomide/dexamethasone (Ld therapy) was initiated. The symptoms in the bilateral fingers, wrists, and ankles improved with the treatment course, and joint sonography revealed that thickening of tendon sheath and soft tissue masses disappeared after seven courses of Ld therapy. However, MRI still revealed soft tissue masses around the bilateral hip joints. In patients with joint symptoms that do not fulfill the diagnostic criteria for rheumatoid arthritis, differentiation with amyloid arthritis is necessary.

Effect of molecular weight and ratio of poly ethylene glycols’ derivatives in combination with trehalose on stability of freeze-dried IgG

The influence of poly ethylene glycol (PEG) at different molecular weights (MWs) and ratios was studied on the stability of freeze-dried immune globulin G (IgG). PEGs (600–4000 Dalton) at concentrations of 0.5 and 5% W/V were applied in the presence of 40 and 60% W/W of trehalose to prepare freeze-dried IgG formulations. Size-exclusion chromatography, infra-red spectroscopy, differential scanning calorimeter, and gel electrophoresis were performed to characterize lyophilized samples. Pure IgG demonstrated the highest aggregation of 5.77 ± 0.10% after process and 12.66 ± 0.50% as well as 44.69 ± 0.50% upon 1 and 2 months of storage at 45 °C, respectively. 5% W/V of PEGs 4000 in combination with 40% W/W trehalose, significantly suppressed aggregation, 0.05 ± 0.01%, with minimum aggregation rate constant of 0.32 (1/month). The integrity of IgG molecules and secondary conformation were properly preserved in all formulations comparing native IgG. It could be concluded that appropriate concentration and MW of PEGs, prominently augmented stabilizing effect of trehalose on freeze-dried antibody through inserting additional supportive mechanisms of actions.

Quantitative Fluorescence Quenching on Antibody-conjugated Graphene Oxide as a Platform for Protein Sensing

We created an immunosensing platform for the detection of proteins in a buffer solution. Our sensing platform relies on graphene oxide (GO) nanosheets conjugated with antibodies to provide quantitative binding sites for analyte proteins. When analyte proteins and standard fluorescein-labelled proteins are competing for the binding sites, the assay exhibits quantitative fluorescence quenching by GO for the fluorescein-labelled proteins as determined by the analyte protein concentration. Because of this mechanism, measured fluorescence intensity from unquenched fluorescein-labelled protein was shown to increase with an increasing analyte protein concentration. As an alternative to the conventional enzyme-linked immunosorbent assay (ELISA), our method does not require an enzyme-linked second antibody for protein recognition and the enzyme for optical signal measurement. Thus, it is beneficial with its low cost and fewer systematic errors caused by the series of antigen-antibody recognition steps in ELISA. Immune globulin G (IgG) was introduced as a model protein to test our method and our results showed that the limit of detection for IgG was 4.67 pmol mL−1 in the buffer solution. This sensing mechanism could be developed into a promising biosensor for the detection of proteins, which would broaden the spectrum of GO applications in both analytical biochemistry and clinical diagnosis.

The use of amino acids to prepare physically and conformationally stable spray-dried IgG with enhanced aerosol performance

This study investigated the effect of various amino acids on the molecular and thermodynamic stability of IgG (immune globulin G) as well as its aerosol performance. The antibody was spray-dried in the presence of different amino acids (leucine, phenylalanine, cysteine, glycine, lysine and arginine) using 20% and 50% (w/w) amino acid. SEC-HPLC, SDS-PAGE and IR-spectroscopy were performed to evaluate the stability of spray-dried IgG. The in-vitro aerosol performance of the well-stabilized formulations was subsequently assessed. IgG containing phenylalanine at 20 and 50% w/w produced the lowest content of aggregated antibody (1.35 ± 0.24%) and (1.12 ± 0.15%). The application of phenylalanine and cysteine at 50% (w/w) demonstrated the best storage stability (2 month at 45°C) with a rate constant of 0.006/month and enhanced fine particle fractions of 62.43 ± 0.34% and 70.51 ± 0.23%, respectively. Samples containing 50% arginine exhibited significantly perturbed conformation and, consequently, the highest aggregation rate constant of 0.019/month following storage. These results indicate that phenylalanine and cysteine serve as efficacious amino acids for the preparation of IgG dry powder with regard to stability and aerodynamic properties.

Mycoplasma pneumonia in Cerebrospinal Fluids of Febrile Children With Neurologic Manifestations: A Cross Sectional Study: Tehran, Iran

Background: The clinical spectrum of Mycoplasma pneumoniae CNS diseases had a wide range. Encephalitis and meningoencephalitis are the most frequent neurological manifestations, but cases of optic neuritis, transverse myelitis, Guillain-Barre syndrome (GBS), etc. have been reported Objectives: To determine the role of M. pneumonia (using PCR and serologically test) in Cerebro Spinal Fluid (CSF) in febrile children with neurologic manifestations (in comparison with normal CSF). Materials and Methods: This cross sectional study was done in pediatric wards of Rasoul hospital in Tehran between 2008 - 2010 upon 55 febrile cases with neurological signs and 10 controls with normal CSF (simple febrile seizure). The CSF samples tested for M. pneumonia DNA (PCR); and Immune Globulin G (IgG) level. Chi square values < 0.05 were considered statistically significant. Results: Positive PCR found in 1 case with Guillan Barre syndrome (1/53; 2%) and none of controls; IgG-CSF level (Cut off 0.0025) had significant difference between cases and controls (Kappa = 0.27, P Value = 0.000). The lowest and highest IgG level observed in aseptic meningitis, and convulsive cases respectively. 73% sensitivity; 90% specificity; 100% Variance (PPV); 28.8% Net Present Value (NPV) determined for IgG-CSF test. Conclusions: Even, very low amount of CSF-IgG with good specificity (90%); could differentiate cases and controls (P = 0.000). The CSF-IgG test (sensitivity 70%, NPV 28.8%) was weak for ruling out the M. pneumonia in cases. positive PCR was rare (2%) in CSF of cases and controls but is more reliable for diagnosing the recent M. pneumonia infection. We prefer to assay the CSF for both serology and PCR in highly suspicious cases. Anti-microbial or immune modulating therapies had possible benefits.

AB0591 Analysis of rheumatoid arthritis patients who were treated with abatacept with rapid effectiveness from japanese multicenter registry system of biological therapy

BackgroundAbatacept (ABT) is an effective biological agent which has unique mechanism to reduce disease activity of rheumatoid arthritis (RA). Although good continuation rate and safety in ABT treatment was reported,...

AB0339 A retrospective study on rapidness of efficacy in abatacept terapy in patients with rheumatoid arthritis from japanese multicenter registry system

BackgroundAbatacept (ABT) is an effective biological agent which has unique mechanism to reduce disease activity of rheumatoid arthritis (RA). Although good continuation rate and safety in ABT treatment was reported,...

Preparation of a novel skeleton weak anion-exchange monolith by single electron transfer-living radical polymerization for protein separation in high performance liquid chromatography

A novel skeleton weak anion-exchange monolith was prepared by single electron transfer-living radical polymerization (SET-LRP) for high performance liquid chromatography (HPLC). In this study, vinyl ester resin was used as the monomer, ethyleneglycol dimethacrylate as the cross linking agent, carbon tetrachloride as the initiator, ferrous powder as the catalyst, and N,N,N′,N′-tetramethylethylenediamine as the ligand to supply amine-groups. The polymerization conditions were optimized. The characters of the monolith were investigated by scanning electron microscopy, Fourier transform infrared spectroscopy and mercury porosimeter, respectively. Good skeleton structure properties were obtained. Moreover, the prepared monolith was used as HPLC stationary phase to separate immune globulin G (IgG) from human plasma with high efficiency. The influences of buffer concentration and pH of the mobile phase on the separation of IgG were investigated. In addition, the monolith was also used to separate the mixture of beef serum albumin (BSA), IgG and lysozyme (Lys) successfully.

Preparation of a strong-cation exchange monolith by a novel method and its application in the separation of IgG on high performance liquid chromatography

A strong cation-exchange poly(vinyl carboxylate-co-ethyleneglycol dimethacrylate) (poly(VC-co-EDMA)) monolithic column for high performance liquid chromatography (HPLC) has been prepared firstly by atom transfer radical polymerization (ATRP) without the expensive complexing ligand, in which vinyl carboxylate was used as the monomer, ethyleneglycol dimethacrylate as the cross linking agent, carbon tetrachloride as the initiator and ferrous chloride as the catalyst. Conditions of the polymerization have been studied and optimized. Morphology of monolithic materials was studied by scanning electronic microscopy. Chemical groups of the monolith were assayed by infrared spectra method and the pore size distribution was determined by a mercury porosimeter. Moreover, the monolith was modified to bear strong-cation exchange groups and tested on the separation of human immune globulin G (IgG) from human plasma in conjunction with HPLC. Good resolution was obtained in a short time (10min) in the separation. The effects of pH and buffer concentration on the elution of IgG have been investigated. Moreover, frontal analytical method was used to get the IgG dynamic banding capacity of the monolith that was 3.0mgg−1. Besides, the monolith was also used to separate lysozyme from egg white and separate the mixture of papain, snailase and IgG.

Tapered Optical Fiber Sensor for Label-Free Detection of Biomolecules

This paper presents a fast, highly sensitive and low-cost tapered optical fiber biosensor that enables the label-free detection of biomolecules. The sensor takes advantage of the interference effect between the fiber’s first two propagation modes along the taper waist region. The biomolecules bonded on the taper surface were determined by demodulating the transmission spectrum phase shift. Because of the sharp spectrum fringe signals, as well as a relatively long biomolecule testing region, the sensor displayed a fast response and was highly sensitive. To better understand the influence of various biomolecules on the sensor, a numerical simulation that varied biolayer parameters such as thickness and refractive index was performed. The results showed that the spectrum fringe shift was obvious to be measured even when the biolayer was only nanometers thick. A microchannel chip was designed and fabricated for the protection of the sensor and biotesting. Microelectromechanical systems (MEMS) fabrication techniques were used to precisely control the profile and depth of the microchannel on the silicon chip with an accuracy of 2 μm. A tapered optical fiber biosensor was fabricated and evaluated with an Immune globulin G (IgG) antibody-antigen pair.

Intravenous Immune Globulin Has Effects on Superantigen-Induced Cytokine Synthesis

Increased incidences of invasive group A streptococcal infections occurred in the Western Society in the 1980s, and the number of streptococcal toxic shock syndrome (STSS) cases continue to rise. Among the hypotheses entertained to explain the pathogenesis of STSS has been the concept that streptococcal superantigens (Sags), including streptococcal pyrogenic exotoxins (SPEs), can trigger potent inflammatory responses and release of cytokines of TH 1 type (TNF-oc, IL-1 IFN-γ and TNF-β). These may mediate tissue damage, organ failure, and shock.Pooled human immune globulin G (IgG) preparations for intravenous administration (ivIgG) have been used in many inflammatory conditions due to their immunomodulatory potential. The effector mechanisms are incompletely understood. This study dealt with the effects of ivIgG on cytokine production in vitro. Cytokine synthesis was identified at the single-cell level using cytokine-specific monoclonal antibodies (mAb) and indirect immunocytochemical techniques. The super-antigen streptococcal Pyrogenic exotoxin-A (SPE-A) induced vigorous cell activation and extensive cytokine synthesis. ivIgG was added either at the beginning or 24 h after the initiation of cultures of peripheral blood mononuclear cells (PBMNC) in order to elucidate the importance of direct toxin neutralization. Addition of IVlg (6 mg/ml) from the beginning of cultures induced a strong reduction of blast transformation and an almost complete inhibition of lymphokine production, in particular of IFN-γ and TNF-β. Supplementation of ivIgG 24 h after initiation of cultures also led to a significant decrease

Immune Globulin Characterization of Complement Fixing Antibodies in Histoplasmic Infection

Complement fixing antibody activity against mycelial phase and yeast phase antigen of H capsulatum has been studied in immune globulin fractions of serum from 13 patients with proved histoplasmosis. Immune globulin G (IgG) specific complement fixing activity was predominant in the human serum regardless of which antigen was used in both acute and nonacute cases. Immune globulin M (IgM) activity was noted in the three cases of primary histoplasmosis, the two epidemic cases and in two of three disseminated cases. No IgM activity was noted in three of five chronic cases. It appears as if infection with Histoplasma capsulatum elicits an immune globulin response in humans which qualitatively is similar to that seen in acute and chronic brucellosis and acute and recrudescent typhus. Complement fixing antibody activity against mycelial phase and yeast phase antigen of H capsulatum has been studied in immune globulin fractions of serum from 13 patients with proved histoplasmosis. Immune globulin G (IgG) specific complement fixing activity was predominant in the human serum regardless of which antigen was used in both acute and nonacute cases. Immune globulin M (IgM) activity was noted in the three cases of primary histoplasmosis, the two epidemic cases and in two of three disseminated cases. No IgM activity was noted in three of five chronic cases. It appears as if infection with Histoplasma capsulatum elicits an immune globulin response in humans which qualitatively is similar to that seen in acute and chronic brucellosis and acute and recrudescent typhus.