Health, Medicine

Immunoglobulin Glycosylation Effects in Allergy and Immunity

Abstract


Purpose of Review

The aim of this review will be to familiarize the reader with the general area of antibody (Ab) glycosylation and to summarize the known functional roles of glycosylation and how glycan structure can contribute to various disease states with emphasis on allergic disease.


Recent Findings

Both immunoglobulin (Ig) isotype and conserved Fc glycosylation sites often dictate the downstream activity of an Ab where complexity and degree of glycosylation contribute to its ability to bind Fc receptors (FcRs) and activate complement. Most information on the effects of glycosylation center on IgG in cancer therapy and autoimmunity. In cancer therapy, glycosylation modifications that enhance affinity for activating FcRs are utilized to facilitate immune-mediated tumor cell killing. In autoimmunity, disease severity has been linked to alterations in the presence, location, and composition of Fc glycans. Significantly less is understood about the role of glycosylation in the setting of allergy and asthma. However, recent data demonstrate that glycosylation of IgE at the asparagine-394 site of Cε3 is necessary for IgE interaction with the high affinity IgE receptor but, surprisingly, glycosylation has no effect on IgE interaction with its low-affinity lectin receptor, CD23.


Summary

Variations in the specific glycoform may modulate the interaction of an Ig with its receptors. Significantly more is known about the functional effects of glycosylation of IgG than for other Ig isotypes. Thus, the role of glycosylation is much better understood in the areas of autoimmunity and cancer therapy, where IgG is the dominant isotype, than in the field of allergy, where IgE predominates. Further work is needed to fully understand the role of glycan variation in IgE and other Ig isotypes with regard to the inhibition or mediation of allergic disease.

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http://ift.tt/2dWu2on

Health, Medicine

Interleukin-5 Antagonists Usher in a New Generation of Asthma Therapy

Abstract

Asthma is the most common chronic respiratory disease in the USA. A subset of patients with asthma have refractory symptoms, persistent eosinophilic inflammation, and recurrent exacerbations despite maximal medical therapy. The monoclonal antibodies targeting the IL-5 pathway are a new class of medications designed to target severe eosinophilic asthma. There are two medications clinically available: mepolizumab and reslizumab, both of which target IL-5. A third medication, benralizumab, is currently under development and targets the IL-5 receptor. Clinical data suggest these medications can reduce asthma exacerbations and improve lung function in patients with peripheral eosinophilia and poorly controlled asthma despite maximal medical therapy. The anti-IL-5 medications are among the first targeted molecular therapies for asthma and will usher in an exciting new era in the treatment of severe asthma.

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Health, Medicine

The Reemergence of the Asthma-COPD Overlap Syndrome: Characterizing a Syndrome in the Precision Medicine Era

Abstract


Purpose of Review

The asthma-COPD overlap syndrome (ACOS) has reemerged in the medical literature. This review addresses our current understanding of ACOS as a clinical and biological entity and how new and existing therapies may be targeted to this group.


Recent Findings

Many studies suggest that ACOS is common and associated with more morbidity than asthma and COPD in general. However, there is no consensus on an ACOS definition, likely due to the heterogeneity of the disease. Variable definitions have led to variable results in ACOS studies. Given this clinical variability, biomarkers (e.g., eosinophils and type 2 inflammatory markers) are increasingly being used to identify an ACOS molecular phenotype which appears to be more responsive to inhaled corticosteroids.


Summary

Although ACOS has become a popular diagnosis, it is unclear whether identifying ACOS as a separate disease entity is clinically useful. Future studies should focus on identifying key clinical features and biomarkers that characterize vulnerable and treatment-responsive patients.

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Health, Medicine

Oral mucosal epithelial cells express the membrane anchored mucin MUC1

S00039969.gif

Publication date: January 2017
Source:Archives of Oral Biology, Volume 73
Author(s): Helena Ukkonen, Paula Pirhonen, Maria Herrala, Jopi J.W. Mikkonen, Surya P. Singh, Raija Sormunen, Arja M. Kullaa
ObjectiveThe presence of a stable salivary pellicle (SP) is essential to provide a wet surface for the oral mucosal epithelia. The oral mucosa is covered by the SP which is suggested to be a mixed film of both salivary and epithelial components. Our aim was to analyse the presence of membrane-anchored mucin MUC1 in the oral mucosal epithelia.DesingThe presence of MUC1 was studied by immunohistochemical and immunoelectron microscopical methods in 19 buccal mucosal specimens. The localization and intensity of the epithelial expression were analyzed.ResultsStrong staining of MUC1 was found in the epithelial cells of intermediate and superficial layers. Some basal cells were shown faint expression. In the intermediate and superficial layers, the MUC1 expression was seen mainly on the upper cell surface. Furthermore, the expression of MUC1 was noted in the cytoplasm near the nucleus and in the rough granules. By electron microscopy, extracellular domain of membrane-anchored molecules extruded about 15–30nm above the cell surface in the apical cells of the oral epithelium. Immunoelectron microscopic examination shows that MUC1 is mainly localized in the plasma membrane of epithelial cells and also in small vesicles (75–100nm) just below the plasma membrane.ConclusionThe membrane-anchored MUC1 is expressed in the superficial layer of the oral mucosal epithelium, especially on the upper surface of epithelial cells. MUCI may be the anchoring protein of the salivary pellicle stabilization.

http://ift.tt/2eVoEyr

http://ift.tt/2egp3NI

Health, Medicine

Oral mucosal epithelial cells express the membrane anchored mucin MUC1

S00039969.gif

Publication date: January 2017
Source:Archives of Oral Biology, Volume 73
Author(s): Helena Ukkonen, Paula Pirhonen, Maria Herrala, Jopi J.W. Mikkonen, Surya P. Singh, Raija Sormunen, Arja M. Kullaa
ObjectiveThe presence of a stable salivary pellicle (SP) is essential to provide a wet surface for the oral mucosal epithelia. The oral mucosa is covered by the SP which is suggested to be a mixed film of both salivary and epithelial components. Our aim was to analyse the presence of membrane-anchored mucin MUC1 in the oral mucosal epithelia.DesingThe presence of MUC1 was studied by immunohistochemical and immunoelectron microscopical methods in 19 buccal mucosal specimens. The localization and intensity of the epithelial expression were analyzed.ResultsStrong staining of MUC1 was found in the epithelial cells of intermediate and superficial layers. Some basal cells were shown faint expression. In the intermediate and superficial layers, the MUC1 expression was seen mainly on the upper cell surface. Furthermore, the expression of MUC1 was noted in the cytoplasm near the nucleus and in the rough granules. By electron microscopy, extracellular domain of membrane-anchored molecules extruded about 15–30nm above the cell surface in the apical cells of the oral epithelium. Immunoelectron microscopic examination shows that MUC1 is mainly localized in the plasma membrane of epithelial cells and also in small vesicles (75–100nm) just below the plasma membrane.ConclusionThe membrane-anchored MUC1 is expressed in the superficial layer of the oral mucosal epithelium, especially on the upper surface of epithelial cells. MUCI may be the anchoring protein of the salivary pellicle stabilization.

http://ift.tt/2eVoEyr

http://ift.tt/2f2J2AG

Health, Medicine

Immunoglobulin Glycosylation Effects in Allergy and Immunity

Abstract

Purpose of Review

The aim of this review will be to familiarize the reader with the general area of antibody (Ab) glycosylation and to summarize the known functional roles of glycosylation and how glycan structure can contribute to various disease states with emphasis on allergic disease.

Recent Findings

Both immunoglobulin (Ig) isotype and conserved Fc glycosylation sites often dictate the downstream activity of an Ab where complexity and degree of glycosylation contribute to its ability to bind Fc receptors (FcRs) and activate complement. Most information on the effects of glycosylation center on IgG in cancer therapy and autoimmunity. In cancer therapy, glycosylation modifications that enhance affinity for activating FcRs are utilized to facilitate immune-mediated tumor cell killing. In autoimmunity, disease severity has been linked to alterations in the presence, location, and composition of Fc glycans. Significantly less is understood about the role of glycosylation in the setting of allergy and asthma. However, recent data demonstrate that glycosylation of IgE at the asparagine-394 site of Cε3 is necessary for IgE interaction with the high affinity IgE receptor but, surprisingly, glycosylation has no effect on IgE interaction with its low-affinity lectin receptor, CD23.

Summary

Variations in the specific glycoform may modulate the interaction of an Ig with its receptors. Significantly more is known about the functional effects of glycosylation of IgG than for other Ig isotypes. Thus, the role of glycosylation is much better understood in the areas of autoimmunity and cancer therapy, where IgG is the dominant isotype, than in the field of allergy, where IgE predominates. Further work is needed to fully understand the role of glycan variation in IgE and other Ig isotypes with regard to the inhibition or mediation of allergic disease.

http://ift.tt/2eTePRL

http://ift.tt/2foBYQf

Health, Medicine

Interleukin-5 Antagonists Usher in a New Generation of Asthma Therapy

Abstract

Asthma is the most common chronic respiratory disease in the USA. A subset of patients with asthma have refractory symptoms, persistent eosinophilic inflammation, and recurrent exacerbations despite maximal medical therapy. The monoclonal antibodies targeting the IL-5 pathway are a new class of medications designed to target severe eosinophilic asthma. There are two medications clinically available: mepolizumab and reslizumab, both of which target IL-5. A third medication, benralizumab, is currently under development and targets the IL-5 receptor. Clinical data suggest these medications can reduce asthma exacerbations and improve lung function in patients with peripheral eosinophilia and poorly controlled asthma despite maximal medical therapy. The anti-IL-5 medications are among the first targeted molecular therapies for asthma and will usher in an exciting new era in the treatment of severe asthma.

http://ift.tt/2eZPMPR

http://ift.tt/2e6PTEA