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Antibody glycosylation: an emerging biomarker of disease activity/protection
Author(s) -
Alter Galit
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.405.4
Subject(s) - antibody dependent cell mediated cytotoxicity , glycosylation , antibody , biology , immune system , monoclonal antibody , immunology , fucosylation , virology , glycan , glycoprotein , biochemistry , microbiology and biotechnology
Beyond their role in neutralization, antibodies mediate a broad array of functions including phagocytosis, cytotoxicity and maintaining immune homeostasis. This range of activities is controlled by two modifications to the constant domain of the antibody; genomic selection of isotype/subclass and post‐translational glycosylation. Mounting evidence suggests that antibody glycosylation changes rapidly and widely in the setting of infectious diseases, acting as a critical biomarker of disease activity. For example, agalactosylation is a marker of active human immunodeficiency virus (HIV), Mycobacterium tuberculosis (MTb) and Ebola virus infections. However, other sugars are controlled more tightly, such as fucose levels, which control antibody dependent cellular cytotoxicity. In fact, fucose levels are selectively reduced in the setting of “controlled” HIV and MTb infections, strongly arguing for different mechanisms of control of particular antibody glycan profiles. Moreover, vaccination studies demonstrate that antibody glycosylation can be actively harnessed and directed by distinct adjuvants, likely offering the humoral immune system a means to tune a broad range of antibody bio‐activities. Thus the emerging studies aimed at dissecting and defining the specific antibody glycovariants that emerge in the setting of controlled infectious diseases offers a unique opportunity to not only design more effective monoclonal therapeutics but also to define the mechanism(s) underlying pathogen control and a path to the development of next generation vaccines that may harness the post‐translational tuning of antibody effector function.