Carbohydrate-specific antibodies are widespread among all classes of immunoglobulins. Despite their broad occurrence, little is known about their formation and biological significance. Carbohydrate-specific antibodies are often classified as natural antibodies under the assumption that they arise without prior exposure to exogenous antigens. On the other hand, various carbohydrate-specific antibodies, including antibodies to ABO blood group antigens, emerge after the contact of immune cells with the intestinal microbiota, which expresses a vast diversity of carbohydrate antigens. Here we explore the development of carbohydrate-specific antibodies in humans, addressing the definition of natural antibodies and the production of carbohydrate-specific antibodies upon antigen stimulation. We focus on the significance of the intestinal microbiota in shaping carbohydrate-specific antibodies not just in the gut, but also in the blood circulation. The structural similarity between bacterial carbohydrate antigens and surface glycoconjugates of protists, fungi and animals leads to the production of carbohydrate-specific antibodies protective against a broad range of pathogens. Mimicry between bacterial and human glycoconjugates, however, can also lead to the generation of carbohydrate-specific antibodies that cross-react with human antigens, thereby contributing to the development of autoimmune disorders.

hFABP3, 4 and 5 are expressed at the human BBB and bind differentially to a diverse range of lipophilic drugs. The unique expression and binding patterns of hFABPs at the BBB may therefore influence drug disposition into the brain.

Inflammatory bowel disease is associated with intestinal dysbiosis and with elevated antibody production toward microbial epitopes. The underlying processes linking the gut microbiota with inflammation are still unclear. Considering the constant induction of antibodies by gut microbial glycans, the aim of this study was to address whether the repertoire of carbohydrate-specific antibodies is altered in Crohn's disease or ulcerative colitis. IgG and IgM reactivities to oligosaccharides representative of mucosal glycans were tested in blood serum from 20 healthy control subjects, 17 ulcerative colitis patients, and 23 Crohn's disease patients using glycan arrays. An increased IgG and IgM reactivity toward fucosylated oligosaccharides was detected in Crohn's disease but not in ulcerative colitis. To address the antibody reactivity to the gut microbiota, IgG binding to members of a complex intestinal microbiota was measured and observed to be increased in sera of patients with Crohn's disease. Based on the elevated reactivity to fucosylated oligosaccharides, gut bacteria were tested for recognition by the fucose-binding Aleuria aurantia lectin. Bacteroides stercoris was detected in IgG-and lectin-positive fractions and reactivity of A. aurantia lectin was demonstrated for additional Bacteroides species. IgG reactivity to these Bacteroides species was significantly increased in inflammatory bowel disease patients, indicating that the increased reactivity to fucosylated oligosaccharides detected in Crohn's disease may be induced by fucose-carrying intestinal bacteria. Enhanced antibody response to fucosylated epitopes may have systemic effects by altering the binding of circulating antibodies to endogenous glycoproteins.

Despite the prominence of carbohydrate-specific antibodies in human sera, data on their emergence and antigen specificities are limited. Whereas maternal IgG are transferred prenatally to the fetal circulation, IgM present in cord blood originate from fetal B lymphocytes. Considering the limited exposure of the fetus to foreign antigens, we assessed the repertoire of carbohydrate-specific antibodies in human cord blood and matched maternal blood samples using glycan arrays. Carbohydrate-specific IgM was absent in cord blood, whereas low cord blood IgG reactivity to glycans was detectable. Comparing IgG reactivities of matched pairs, we observed a general lack of correlation in the antigen specificity of IgG from cord blood and maternal blood due to a selective exclusion of most carbohydrate-specific IgG from maternofetal transfer. Given the importance of intestinal bacteria in inducing carbohydrate-specific antibodies, we analyzed global antibody specificities toward commensal bacteria. Similar IgG reactivities to specific Bacteroides species were detected in matched cord and maternal blood samples, thus pointing to an efficient maternal transfer of anti-microbial IgG. Due to the observed selectivity in maternofetal IgG transfer, the lack of fetal antibodies to carbohydrate epitopes is only partially compensated by maternal IgG, thus resulting in a weak response to carbohydrate antigens in neonates.

Background:The skin is primarily affected by aging, especially when it is exposed to particulate matter present in the environment. It has been hypothesized that consumption of products with known antioxidant properties would help combat factors associated with both intrinsic and extrinsic aging factors. Objective:The aim of the present study was to evaluate the effect of the formulation Blue Fenugreek Kale Extract (BFKE) on skin aging. Methods: In this study, the effect of BFKE on protein oxidation was determined in human dermal fibroblasts by analysis of the level of protein carbonylation after cells were stressed with either H 2 O 2 or urban pollution consisting of particulate matter and UV-A. Furthermore, a randomized, double-blind, placebo-controlled clinical study that evaluated the effect of BFKE consumption over a period of 56 days in 59 volunteers was performed. The major parameter studied was skin barrier dysfunction through the assessment of Transepidermal Water Loss (TEWL). Additional parameters analyzed clinically include skin moisture content, participant selfassessment of skin parameters, wrinkle severity, skin sagging and elasticity. Furthermore, low grade and allergic inflammatory biomarker levels were measured at the start and end of the treatment period, along with oxidative stress assessment using blood malondialdehyde levels. Results: BFKE significantly reduced protein carbonylation in human dermal fibroblasts stressed with urban pollution. In the clinical study, the TEWL level reduced significantly and at the same time the skin moisture content levels increased by end of the treatment period. No significant changes were observed in wrinkle severity, skin sagging, elasticity, inflammatory and oxidative stress biomarker levels. Participant and investigator perception of treatment was significantly greater after product consumption, as was the improvement in skin parameters based on participant self-assessment. Conclusion: BFKE reduces protein oxidation induced by H 2 O 2 and restores skin barrier function and skin hydration, while also combating early signs of aging.

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