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Galactosylation of Serum IgA1 O-Glycans in Celiac Disease

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Abstract

In celiac disease, gluten ingestion provokes small-bowel mucosal injury and production of IgA autoantibodies against transglutaminase 2 (TG2). It has been suggested that in celiac patients IgA could mediate the transepithelial passage of gluten peptides in a mechanism involving the transferrin receptor. As IgA1 with galactose-deficient O-linked glycans has elevated affinity for the transferrin receptor, we assessed whether total serum IgA1 and IgA1 anti-TG2 autoantibodies in celiac patients are aberrantly glycosylated. We report that males with celiac disease have higher total serum levels of galactose-deficient IgA1 than non-celiac males. Furthermore, O-glycans of the disease-specific TG2 IgA1 autoantibodies in celiac patients exhibited elevated galactose deficiency. A gluten-free diet had no effect on the total serum levels of galactose-deficient IgA1, whereas the amount of galactose-deficient anti-TG2 IgA1 decreased. Thus, the undergalactosylated IgA1 molecules are not pathognomonic for celiac disease, but galactose deficiency in IgA1 could be an aggravating factor.

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Acknowledgements

The Celiac Disease Study Group has been financially supported by the Academy of Finland, the Sigrid Juselius Foundation, the Pediatric Research Foundation, the Competitive Research Funding of Tampere University Hospital, the Research Fund of the Finnish Celiac Society and the European Commission (contract number MRTN-CT-2006-036032). HS and JN were supported in part by grants from the National Institute of Health DK078244, DK080301, DK082753, DK083663, DK071802, and DK077279.

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Authors and Affiliations

  1. Pediatric Research Center, University of Tampere and Tampere University Hospital, Finn-Medi 3, FIN-33014, Tampere, Finland

    Katri Lindfors & Markku Mäki

  2. Department of Microbiology, University of Alabama at Birmingham, Alabama, USA

    Hitoshi Suzuki & Jan Novak

  3. Department of Nephrology, Juntendo University Faculty of Medicine, Tokyo, Japan

    Hitoshi Suzuki

  4. Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, Tampere, Finland

    Pekka Collin & Katri Kaukinen

  5. Department of Medical Genetics and Research Program for Molecular Medicine, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland

    Päivi Saavalainen & Lotta L. E. Koskinen

  6. Medical School, University of Tampere, Finn-Medi 3, 33014, Tampere, Finland

    Katri Lindfors & Katri Kaukinen

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  1. Katri Lindfors
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  2. Hitoshi Suzuki
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  3. Jan Novak
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  4. Pekka Collin
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  5. Päivi Saavalainen
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  6. Lotta L. E. Koskinen
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  7. Markku Mäki
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  8. Katri Kaukinen
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Correspondence to Katri Lindfors.

Additional information

Katri Lindfors and Hitoshi Suzuki contributed equally to this study

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Lindfors, K., Suzuki, H., Novak, J. et al. Galactosylation of Serum IgA1 O-Glycans in Celiac Disease. J Clin Immunol 31, 74–79 (2011). https://doi.org/10.1007/s10875-010-9473-7

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  • DOI: https://doi.org/10.1007/s10875-010-9473-7

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