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Sialic Acid Residues Are Essential for the Anaphylactic Activity of Murine IgG1 Antibodies¹

Sandriana R. Silva^*, Adriana Casabuono, Jacqueline F. Jacysyn^*, Bruna C. Favoretto^*, Irene Fernandes, Mahasti S. Macedo^*, Alicia S. Couto and Eliana L. Faquim-Mauro^2,

^* Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil; Centro de Investigaciones en Hidratos de Carbano, Department of Organic Chemistry, Buenos Aires University, Buenos Aires, Argentina; and Butantan Institute, São Paulo, Brazil

Glycosylation of the Ab molecule is essential for maintaining the functional structure of Fc region and consequently for Ab-mediated effector functions, such as binding to cells or complement system activation. Alterations in the composition of the sugar moiety can dramatically influence Ab activity; however, it is not completely clear how differences in the N-linked oligosaccharide structure impact the biological function of Abs. We have described that murine IgG1 Abs can be separated according to their ability to elicit in vivo anaphylaxis in a fraction of anaphylactic and other of non-anaphylactic molecules. Furthermore, we showed that the N-linked oligosaccharide chain is essential for the structural conformation of the anaphylactic IgG1, the binding to FcRIII on mast cells, and, consequently, for the ability to mediate anaphylactic reactions. In this study, we evaluated the contribution of individual sugar residues to this biological function. Differences in the glycan composition were observed when we analyzed oligosaccharide chains from anaphylactic or non-anaphylactic IgG1, mainly the presence of more sialic acid and fucose residues in anaphylactic molecules. Interestingly, the enzymatic removal of terminal sialic acid residues in anaphylactic IgG1 resulted in loss of the ability to trigger mast cell degranulation and in vivo anaphylactic reaction, similarly to the deglycosylated IgG1 Ab. In contrast, fucose removal did not affect the anaphylactic function. Therefore, we demonstrated that the ability of murine IgG1 Abs to mediate anaphylaxis is directly dependent on the amount of sialic acid residues associated to the oligosaccharide chain attached to the Fc region of these molecules.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by Fundacao de Amparo a Pesquisa do Estado de Sao Paulo Conselho Nacional de Pesquisa, Comissao de Aperfeicoamento de Pessoal de Nival Superior, Universidad de Buenos Aires, and Consejo Nacional de Investigaciones Cientificas y Tecnicas de Argentina (Argentina).

² Address correspondence and reprint requests to Dr. Eliana L. Faquim-Mauro, Av. Vital Brasil, 1500, 05503-900 São Paulo, SP, Brasil. E-mail address: elianafaquim{at}butantan.gov.br

³ Abbreviations used in this paper: HPAEC-PAD, high pH anion exchange chromatography; PCA, passive cutaneous anaphylactic; PNGase F, N-glycosidase F; SNA, Sambucus nigra.