Intravenous immunoglobulin contains a broad repertoire of anticarbohydrate antibodies that is not restricted to the IgG2 subclass

• Published in: Journal of allergy and clinical immunology Vol. 123; no. 6; pp. 1268 - 1276.e15
• Main Authors: von Gunten, Stephan, MD, PhD, MME, Smith, David F., PhD, Cummings, Richard D., PhD, Riedel, Stefan, MD, PhD, Miescher, Sylvia, PD, PhD, Schaub, Alexander, PhD, Hamilton, Robert G., PhD, Bochner, Bruce S., MD
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier 01.06.2009; Elsevier Limited
• Subjects: Allergy and Immunology; Antibodies - immunology; Bacteria - immunology; Binding sites; Biological and medical sciences; Carbohydrates; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; Immunoglobulin G - immunology; Immunoglobulins, Intravenous - immunology; Immunopathology; Ligands; Medical sciences; Microarray Analysis; Polysaccharides - immunology; Proteins; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Bacterial Carbohydrate Structure Database; CFG; CPS; Lipoteichoic acid; Ganglioside GalNAcβ(1-4)[NeuAc(α2-3)]Galβ(1-4)Glcβ(1-1′)-ceramide; GM1; sTn; glycan microarray; GM2; glycans; Ganglioside NeuAc(α2-8)NeuAc(α2-3)Galβ(1-4)Glcβ(1-1′)-ceramide; Ganglioside Galβ(1-4)GalNAcβ(1-4)[NeuAc(α2-3)]Galβ(1-4)Glcβ(1-1′)-ceramide; Consortium for Functional Glycomics; sLe x; Sulfated; su; Ganglioside GalNAcβ(1-4)[NeuAc(α2-8)NeuAc(α2-3)]Galβ(1-4)Glcβ(1-1′)-ceramide; Intravenous immunoglobulin; IVIG; Sialyl Lewis X; IgG 2; BCSDB; GD2; Sialyl Tn (Thomsen-Friedenreich precursor) antigen: Neu5Ac(α2-6)GalNAcα-O-Ser/Thr; IgG subclasses; GD3; anticarbohydrate antibodies; LTA; γ-globulin; Capsular polysaccharide; Immunopathology; IgA; Immunoglobulins; Intravenous administration; Antibody; IgG; IgG2; Globulin; Glycan; Immunology; Immunologic repertoire
• ISSN: 0091-6749; 1097-6825; 1097-6825
• DOI: 10.1016/j.jaci.2009.03.013

Background Specificities for carbohydrate IgG antibodies, thought to be predominantly of the IgG2 subclass, have never been broadly examined in healthy human subjects. Objective To examine commercial intravenous immunoglobulin (IVIG) preparations for their ability to recognize a wide range of glycans and to determine the contribution of IgG2 to the binding pattern observed. Methods We used a glycan microarray to evaluate IVIG preparations and a control mix of similar proportions of human myeloma IgG1 and IgG2 for binding to 377 glycans, courtesy of the Consortium for Functional Glycomics Core H. Glycans recognized were categorized using public databases for their likely cellular sources. IgG2 was depleted from IVIG by using immunoaffinity chromatography, and depletion was confirmed by using nephelometry and surface plasmon resonance. Results Nearly half of the glycans bound IgG. Some of the glycans with the greatest antibody binding can be found in structures of human pathogenic bacteria (eg, Streptococcus pneumoniae, Mycobacterium tuberculosis, Vibrio cholera ) and nonpathogenic bacteria, including LPS and lipoteichoic acid, capsular polysaccharides, and exopolysaccharides. Surprisingly, depletion of IgG2 had only a modest effect on anticarbohydrate recognition patterns compared with the starting IVIG preparation. Little to no binding activity was detected to human endogenous glycans, including tumor-associated antigens. Conclusions This novel, comprehensive analysis provides evidence that IVIG contains a much wider range than previously appreciated of anticarbohydrate IgG antibodies, including those recognizing both pathogenic and non–pathogen-associated prokaryotic glycans.