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Aberrant O-glycosylation and anti-glycan antibodies in an autoimmune disease IgA nephropathy and breast adenocarcinoma

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Abstract

Glycosylation abnormalities have been observed in autoimmune diseases and cancer. Here, we compare mechanisms of aberrant O-glycosylation, i.e., formation of Tn and sialyl-Tn structures, on MUC1 in breast cancer, and on IgA1 in an autoimmune disease, IgA nephropathy. The pathways of aberrant O-glycosylation, although different for MUC1 and IgA1, include dysregulation in glycosyltransferase expression, stability, and/or intracellular localization. Moreover, these aberrant glycoproteins are recognized by antibodies, although with different consequences. In breast cancer, elevated levels of antibodies recognizing aberrant MUC1 are associated with better outcome, whereas in IgA nephropathy, the antibodies recognizing aberrant IgA1 are part of the pathogenetic process.

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Acknowledgments

This work was supported in part by grants from the National Institutes of Health DK082753, DK078244, DK083663, DK075868, DK077279, and GM098539, a grant from the IGA Nephropathy Foundation of America, and by grants and LH11046 Ministry of School, Youth, and Sport, GAP302/10/1055 Czech Science Foundation, NT11081 Grant Agency of the Ministry of the Health, Czech Republic.

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  1. Department of Immunology, Faculty of Medicine and Dentistry, Palacky University, Hněvotínská 3, 77515, Olomouc, Czech Republic

    Milada Stuchlová Horynová & Milan Raška

  2. Department of Microbiology, University of Alabama at Birmingham, 845 19th St. S., BBRB 762, Birmingham, AL, 35294, USA

    Milada Stuchlová Horynová & Milan Raška

  3. Center for Glycomics, Departments of Cellular and Molecular Medicine, University of Copenhagen, Blegdamsvej 3, 2200, Copenhagen N, Denmark

    Henrik Clausen

  4. Department of Microbiology, University of Alabama at Birmingham, 845 19th St. S., BBRB 761A, Birmingham, AL, 35294, USA

    Jan Novak

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Stuchlová Horynová, M., Raška, M., Clausen, H. et al. Aberrant O-glycosylation and anti-glycan antibodies in an autoimmune disease IgA nephropathy and breast adenocarcinoma. Cell. Mol. Life Sci. 70, 829–839 (2013). https://doi.org/10.1007/s00018-012-1082-6

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