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Immune activation of Bio-Germanium in a randomized, double-blind, placebo-controlled clinical trial with 130 human subjects: Therapeutic opportunities from new insights.
Cho, JM, Chae, J, Jeong, SR, Moon, MJ, Shin, DY, Lee, JH
PloS one. 2020;(10):e0240358
Abstract
[NCT03677921]; www.clinicaltrials.gov [KCT0002726]; https://cris.nih.go.kr.
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2.
Glycation and Oxidative Stress Increase Autoantibodies in the Elderly.
Khan, MWA, Al Otaibi, A, Sherwani, S, Khan, WA, Alshammari, EM, Al-Zahrani, SA, Saleem, M, Khan, SN, Alouffi, S
Molecules (Basel, Switzerland). 2020;(16)
Abstract
Aging causes gradual changes in free radicals, antioxidants, and immune-imbalance in the elderly. This study aims to understand links among aging, gluco-oxidative stress, and autoantibodies in asymptomatic individuals. In vitro glycation of human serum albumin (Gly-HSA) induces appreciable biochemical changes. Significant inhibition of advanced glycation end products (AGEs) formation was achieved using garlic extract (53.75%) and epigallocatechin-3-gallate from green tea (72.5%). Increased amounts of serum carbonyl content (2.42 ± 0.5) and pentosidine (0.0321 ± 0.0029) were detected in IV-S (S represent smokers) vs. IV group individuals. Direct binding ELISA results exhibited significantly high autoantibodies against Gly-HSA in group IV-S (0.55 ± 0.054; p < 0.001) and III-S (0.40 ± 0.044; p < 0.01) individuals as compared to the age matched subjects who were non-smokers (group IV and III). Moreover, high average percent inhibition (51.3 ± 4.1%) was obtained against Gly-HSA in IV-S group individuals. Apparent association constant was found to be high for serum immunoglobulin-G (IgG) from group IV-S (1.18 × 10-6 M) vs. serum IgG from IV group (3.32 × 10-7 M). Aging induced gluco-oxidative stress and AGEs formation may generate neo-epitopes on blood-proteins, contributing to production of autoantibodies in the elderly, especially smokers. Use of anti-glycation natural products may reduce age-related pathophysiological changes.
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3.
Repertoire and Neutralizing Activity of Antibodies Against Hepatitis C Virus E2 Peptide in Patients With Spontaneous Resolution of Hepatitis C.
Olbrich, A, Wardemann, H, Böhm, S, Rother, K, Colpitts, CC, Wrensch, F, Baumert, TF, Berg, T, Benckert, J
The Journal of infectious diseases. 2019;(7):1209-1218
Abstract
Neutralizing antibodies can prevent hepatitis C virus (HCV) infection, one of the leading causes of cirrhosis and liver cancer. Here, we characterized the immunoglobulin repertoire of memory B-cell antibodies against a linear epitope in the central front layer of the HCV envelope (E2; amino acids 483-499) in patients who were infected in a single-source outbreak. A reverse transcription polymerase chain reaction-based immunoglobulin gene cloning and recombinant expression approach was used to express monoclonal antibodies from HCV E2 peptide-binding immunoglobulin G-positive memory B cells. We identified highly mutated antibodies with a neutralizing effect in vitro against different genotype isolates sharing similar gene features. Our data confirm the importance of VH1-69 use for neutralizing activity. The data offer a promising basis for vaccine research and the use of anti-E2 antibodies as a means of passive immunization.
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4.
Relationship between serum levels of immunoglobulins and metabolic syndrome in an adult population: A population study from the TCLSIH cohort study.
Wang, X, Fu, J, Gu, Y, Chi, VTQ, Zhang, Q, Liu, L, Meng, G, Yao, Z, Wu, H, Bao, X, et al
Nutrition, metabolism, and cardiovascular diseases : NMCD. 2019;(9):916-922
Abstract
BACKGROUND AND AIMS Metabolic syndrome (MetS) is a combination of metabolic disorders that increase the risk of developing cardiovascular disease, and inflammation is considered as a pathological basis for MetS. Immunoglobulins (Igs) are the major secretory products of the adaptive immune system. However, no large-scale population study has focused on a possible relationship between Igs and MetS. We designed a cross-sectional study to investigate the relationship between Igs and prevalence of MetS in a large-scale adult population. METHODS AND RESULTS A total of 10,289 participants were recruited among residents in Tianjin, China. Metabolic syndrome was defined in accordance with the criteria of the American Heart Association scientific statements of 2009. Serum levels of Igs were determined by immunonephelometry. Multiple logistic regression models were used to assess the relationship between the quintiles of serum levels of Igs and the prevalence of MetS. The overall prevalence of MetS was 36.1%. The mean (standard deviation) values of Igs (IgG, IgE, IgM, and IgA) were 1205.7 (249.3) mg/dL, 93.1 (238.9) IU/mL, 105.7 (57.3) mg/dL, and 236.2 (97.6) mg/dL, respectively. The adjusted odds ratios (95% confidence interval) of MetS for the highest quintile of Igs (IgG, IgE, IgM, and IgA), when compared to the lowest quintile, were 0.81 (0.70, 0.95), 0.97 (0.83, 1.12), 1.13 (0.97, 1.33), and 1.52 (1.30, 1.77), respectively. CONCLUSIONS This study demonstrated that decreased IgG and increased IgA are independently related to a higher prevalence of MetS. The results indicate that the Igs might be useful predictive factors for MetS in the general adult population.
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5.
CMV-Specific Immune Response-New Patients, New Insight: Central Role of Specific IgG during Infancy and Long-Lasting Immune Deficiency after Allogenic Stem Cell Transplantation.
Zdziarski, P
International journal of molecular sciences. 2019;(2)
Abstract
Although the existing paradigm states that cytomegalovirus (CMV) reactivation is under the control of the cellular immune response, the role of humoral and innate counterparts are underestimated. The study analyzed the host⁻virus interaction i.e., CMV-immune response evolution during infection in three different clinical situations: (1) immunodeficient CMV-positive human leukocyte antigen (HLA)-matched bone marrow recipients after immunoablative conditioning as well as immunocompetent, (2) adult, and (3) infant with primary immune response. In the first situation, a fast and significant decrease of specific immunity was observed but reconstitution of marrow-derived B and natural killer (NK) cells was observed prior to thymic origin of T cells. The lowest CMV-IgG (93.2 RU/mL) was found just before CMV viremia. It is noteworthy that the sole and exclusive factor of CMV-specific immune response is a residual recipient antibody class IgG. The CMV-quantiferon increase was detected later, but in the first phase, phytohemagglutinin (PHA)-induced IFN-γ release was significantly lower than that of CMV-induced ("indeterminate" results). It corresponds with the increase of NK cells at the top of lymphocyte reconstitution and undetected CMV-specific CD8 cells using a pentamer technique. In immunocompetent adult (CMV-negative donor), the cellular and humoral immune response increased in a parallel manner, but symptoms of CMV mononucleosis persisted until the increase of specific IgG. During infancy, the decrease of the maternal CMV-IgG level to 89.08 RU/mL followed by clinical sequel, i.e., CMV replication, were described. My observations shed light on a unique host-CMV interaction and CMV-IgG role: they indicate that its significant decrease predicts CMV replication. Before primary cellular immune response development, the high level of residual CMV-IgG (about >100 R/mL) from mother or recipient prevents virus reactivation. The innate immune response and NK-dependent IFN-secretion should be further investigated.
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6.
The Core Fucose on an IgG Antibody is an Endogenous Ligand of Dectin-1.
Manabe, Y, Marchetti, R, Takakura, Y, Nagasaki, M, Nihei, W, Takebe, T, Tanaka, K, Kabayama, K, Chiodo, F, Hanashima, S, et al
Angewandte Chemie (International ed. in English). 2019;(51):18697-18702
Abstract
The core fucose, a major modification of N-glycans, is implicated in immune regulation, such as the attenuation of the antibody-dependent cell-mediated cytotoxicity of antibody drugs and the inhibition of anti-tumor responses via the promotion of PD-1 expression on T cells. Although the core fucose regulates many biological processes, no core fucose recognition molecule has been identified in mammals. Herein, we report that Dectin-1, a known anti-β-glucan lectin, recognizes the core fucose on IgG antibodies. A combination of biophysical experiments further suggested that Dectin-1 recognizes aromatic amino acids adjacent to the N-terminal asparagine at the glycosylation site as well as the core fucose. Thus, Dectin-1 appears to be the first lectin-like molecule involved in the heterovalent and specific recognition of characteristic N-glycans on antibodies.
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7.
The changes of immunoglobulin G N-glycosylation in blood lipids and dyslipidaemia.
Liu, D, Chu, X, Wang, H, Dong, J, Ge, SQ, Zhao, ZY, Peng, HL, Sun, M, Wu, LJ, Song, MS, et al
Journal of translational medicine. 2018;(1):235
Abstract
BACKGROUND Alternative N-glycosylation has significant structural and functional consequences on immunoglobulin G (IgG) and can affect immune responses, acting as a switch between pro- and anti-inflammatory IgG functionality. Studies have demonstrated that IgG N-glycosylation is associated with ageing, body mass index, type 2 diabetes and hypertension. METHODS Herein, we have demonstrated patterns of IgG glycosylation that are associated with blood lipids in a cross-sectional study including 598 Han Chinese aged 20-68 years. The IgG glycome composition was analysed by ultra-performance liquid chromatography. RESULTS Blood lipids were positively correlated with glycan peak GP6, whereas they were negatively correlated with GP18 (P < 0.05/57). The canonical correlation analysis indicated that initial N-glycan structures, including GP4, GP6, GP9-12, GP14, GP17, GP18 and GP23, were significantly correlated with blood lipids, including total cholesterol, total triglycerides (TG) and low-density lipoprotein (r = 0.390, P < 0.001). IgG glycans patterns were able to distinguish patients with dyslipidaemia from the controls, with an area under the curve of 0.692 (95% confidence interval 0.644-0.740). CONCLUSIONS Our findings indicated that a possible association between blood lipids and the observed loss of galactose and sialic acid, as well as the addition of bisecting GlcNAcs, which might be related to the chronic inflammation accompanying with the development and procession of dyslipidaemia.