Dataset Information

Tissue-Specific Expression of the Low-Affinity IgG Receptor, Fc?RIIb, on Human Mast Cells.

ABSTRACT: Immediate hypersensitivity reactions are induced by the interaction of allergens with specific IgE antibodies bound via Fc?RI to mast cells and basophils. While these specific IgE antibodies are needed to trigger such reactions, not all individuals harboring IgE exhibit symptoms of allergy. The lack of responsiveness seen in some subjects correlates with the presence of IgG antibodies of the same specificity. In cell culture studies and in vivo animal models of food allergy and anaphylaxis such IgG antibodies have been shown to exert suppression via Fc?RIIb. However, the reported absence of this inhibitory receptor on primary mast cells derived from human skin has raised questions about the role of IgG-mediated inhibition of immediate hypersensitivity in human subjects. Here, we tested the hypothesis that mast cell Fc?RIIb expression might be tissue specific. Utilizing a combination of flow cytometry, quantitative PCR, and immunofluorescence staining of mast cells derived from the tissues of humanized mice, human skin, or in fixed paraffin-embedded sections of human tissues, we confirm that Fc?RIIb is absent from dermal mast cells but is expressed by mast cells throughout the gastrointestinal tract. IgE-induced systemic anaphylaxis in humanized mice is strongly inhibited by antigen-specific IgG. These findings support the concept that IgG, signaling via Fc?RIIb, plays a physiological role in suppressing hypersensitivity reactions.

SUBMITTER: Burton OT

PROVIDER: S-EPMC5997819 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Tissue-Specific Expression of the Low-Affinity IgG Receptor, FcγRIIb, on Human Mast Cells.

Burton Oliver T OT Epp Alexandra A Fanny Manoussa E ME Miller Samuel J SJ Stranks Amanda J AJ Teague Jessica E JE Clark Rachael A RA van de Rijn Matt M Oettgen Hans C HC

Frontiers in immunology 20180606

Immediate hypersensitivity reactions are induced by the interaction of allergens with specific IgE antibodies bound <i>via</i> FcεRI to mast cells and basophils. While these specific IgE antibodies are needed to trigger such reactions, not all individuals harboring IgE exhibit symptoms of allergy. The lack of responsiveness seen in some subjects correlates with the presence of IgG antibodies of the same specificity. In cell culture studies and <i>in vivo</i> animal models of food allergy and ana ...[more]

PMID: 29928276

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Project description:Essentials Systemic lupus erythematosus (SLE) patients are at increased risk for premature CVD. Platelet activity, vascular dysfunction and carotid artery plaque are associated with FcγRIIA genotype in SLE. FcγRIIA genotype was not associated with platelet activity or carotid plaque in healthy controls. FcγRIIA represents a link that connects platelet activity, vascular health and CVD in SLE. SUMMARY: Background Systemic lupus erythematosus (SLE) is a complex autoimmune disease associated with an elevated risk of premature cardiovascular disease. Platelets express receptors contributing to inflammation and immunity, including FcγRIIA, the low affinity receptor of the Fc portion of IgG antibodies. The variation at a single amino acid substitution, H131R, in the extracellular binding domain alters the affinity for IgG, which may account for individual variation in platelet activity and platelet-mediated disease. Objectives This study was performed to investigate the association between FcγRIIA genotype, preclinical atherosclerosis, platelet reactivity and vascular health. Methods FcγRIIA was genotyped in 80 SLE patients and 30 healthy controls. Carotid ultrasound plaque, soluble E-selectin and platelet aggregability were evaluated in SLE and matched controls. Results Carotid plaque was significantly more prevalent in SLE patients carrying a variant allele compared to those with a homozygous ancestral allele (58% vs. 25%, P = 0.04). In contrast, prevalent carotid plaque was not associated with genotype in controls. Consistently, SLE variant FcγRIIA carriers vs. ancestral allele carriers had a significant increase in the levels of soluble E-selectin, which was not observed in controls. Monocyte and leukocyte-platelet aggregation and platelet aggregation in response to submaximal agonist stimulation were significantly elevated in SLE patients with the variant vs. ancestral genotype. Conclusions Carotid ultrasound plaque, soluble E-selectin levels and platelet activity were more frequently prevalent in SLE patients carrying variant FcγRIIA. The interplay between FcγRIIA-mediated platelet activation and endothelial cells might represent a mechanism underlying the pathogenesis of cardiovascular disease in SLE patients.

Dataset Information

Tissue-Specific Expression of the Low-Affinity IgG Receptor, Fc?RIIb, on Human Mast Cells.

Publications

Tissue-Specific Expression of the Low-Affinity IgG Receptor, FcγRIIb, on Human Mast Cells.

Similar Datasets

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