1. Glycans and glycan-specific IgE in clinical and molecular allergology: Sensitization, diagnostics, and clinical symptoms 
Arne Homann, PhD, Gabriele Schramm, PhD, Uta Jappe, MD, MSc 
Journal of Allergy and Clinical Immunology 
Volume 140, Issue 2, Pages (August 2017)
DOI: /j.jaci
Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

2. Fig 1
Groups of subjects with different sensitization patterns after contact with glycosylated allergens. Many subjects do not have IgE, whereas others form significant allergen-specific IgE. This IgE is directed against glycans (group A) and/or peptides (group B). Although allergy diagnoses for subjects of group B are more frequently covered by molecular allergy diagnostics for several important allergen sources, the interpretation of anti-glycan IgE in patient serum is not clear for the allergologist. After the discovery of the allergen α-Gal, patients with IgE against α-Gal (group A1) can receive correct diagnoses, whereas in the past, the delayed-type anaphylaxis to meat and innards was missed by using allergy in vitro diagnostic tests. However, the allergy diagnosis for patients with IgE to classical CCDs of a different specificity (group A2) remains challenging.
Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci )
Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

3. Fig 2
Structure of N-glycans on allergens. A, Chemical structure (left) and symbol simplification according to Consortium for Functional Glycomics conventions are shown for the N-glycan core glycan. Note that the substitutions of the N-glycan core on allergens are either nonhuman carbohydrates (xylose) or nonhuman carbohydrate linkages and positions (α-1,3 fucosylation on the first GlcNAc of the chitobiose core). B, IgE against classical CCDs are known to cause no or minor allergy symptoms. C, IgE against α-Gal can cause severe allergy symptoms. Nonhuman carbohydrate substitutions of the N-glycan core are indicated by red brackets. The monosaccharide residues in brackets are present or not in different species. PLA2, Phospholipase A2.
Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci )
Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

4. Fig 3
Selection of nonhuman IgE-binding glycan structures from insects, plants, parasites, and nonhuman mammals. Glycans from different species show a high degree of similarity that results in the often observed human anti-CCD IgE cross-reactivity. Small differences in the carbohydrate structure have pronounced immunologic effects, either foreign monosaccharides, such as xylose and Neu5Gc, or nonhuman carbohydrate linkages, as in the case of α-Gal.
Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci )
Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

5. Fig 4
Immunologic scenarios for clinical significance or nonsignificance of IgE. A, Model for the development of high- versus low-affinity IgE through differential B-cell class-switching.4 B, Activation of FcεR+ cells through receptor cross-linking is dependent on multivalent antigens (allergens). C, The therapeutic mAb CTX is particularly effective in IgE binding and FcεR cross-linking.1 D, IgE binding to allergens might be blocked by allergen-specific IgG.2,3 Consequences of IgG binding to allergens depend on the IgG subclass.
Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci )
Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

6. Fig 5
Association of structure and function of foreign and human-like glycans from allergens and parasites. Top, Representative structures of the predominant N-glycans from S mansoni egg antigens (SEA). Although IPSE/alpha-1 and omega-1 direct the immune system toward TH2, the N-glycan core of kappa-5 is a target of glycan-specific IgE. No IgE is formed against IPSE/alpha-1 or omega Bottom, Glycans mirroring or mimicking human glycan structures and have an effect on the human immune system are indicated in the table. h, Human; i, insect p, plant; s, schistosome. LeX,5,6,11-13 di-N-acetyl-lactosamine (LDN),5,14-21 LDNF,5,6,17,20,22-24 FLDN,5,25-28 and LDNdF “F” indicates conjugated fucose as shown in the respective oligosaccharide structure.
Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci )
Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

7. Fig 6
Immunologic effects of selected carbohydrate receptors on human immune cells. Known carbohydrate ligands and resulting immunologic effects are indicated. Top scheme, Simplified examples of cellular cross-talk on receptor interaction with glycans. Attachment and uptake of glycoproteins with specific N-glycans is mediated, for example, by MR or the DC-SIGN receptor. Cross-linking of IgE, such as by allergens containing α-Gal, and Toll-like receptor (TLR) stimulation by glycan-containing LPS induces proinflammatory cellular responses. MR,33 DC-SIGN,27 sialic acid–binding immunoglobulin-like lectin (SIGLEC),32 selectin,34 macrophage galactose lectin 1 (MGL1),20 epidermal growth factor–like module-containing mucin-like hormone receptor-like 2 (EMR2),35 Toll-like receptor (TLR),30,36 and FcγR.31,37
Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci )
Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions