The architecture of the IgG anti-carbohydrate repertoire in primary antibody deficiencies

Immune system failure in primary antibody deficiencies (PADs) has been linked to recurrent infections, autoimmunity, and cancer, yet clinical judgment is often based on the reactivity to a restricted panel of antigens. Previously, we demonstrated that the human repertoire of carbohydrate-specific im...

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Bibliographic Details
Published in:Blood 2019-11, Vol.134 (22), p.1941-1950
Main Authors: Jandus, Peter, Boligan, Kayluz Frias, Smith, David F., de Graauw, Elisabeth, Grimbacher, Bodo, Jandus, Camilla, Abdelhafez, Mai M., Despont, Alain, Bovin, Nicolai, Simon, Dagmar, Rieben, Robert, Simon, Hans-Uwe, Cummings, Richard D., von Gunten, Stephan
Format: Article
Language:English
Subjects:
Autoantigens - immunology
Carbohydrates - immunology
Epitopes - immunology
Female
Humans
Immunobiology and Immunotherapy
Immunoglobulin G - immunology
Male
Primary Immunodeficiency Diseases - immunology
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Summary:Immune system failure in primary antibody deficiencies (PADs) has been linked to recurrent infections, autoimmunity, and cancer, yet clinical judgment is often based on the reactivity to a restricted panel of antigens. Previously, we demonstrated that the human repertoire of carbohydrate-specific immunoglobulin G (IgG) exhibits modular organization related to glycan epitope structure. The current study compares the glycan-specific IgG repertoires between different PAD entities. Distinct repertoire profiles with extensive qualitative glycan-recognition defects were observed, which are characterized by the common loss of Galα and GalNAc reactivity and disease-specific recognition of microbial antigens, self-antigens, and tumor-associated carbohydrate antigens. Antibody repertoire analysis may provide a useful tool to elucidate the degree and the clinical implications of immune system failure in individual patients. •Repertoire analysis by microarray technology constitutes a powerful tool to evaluate immune system failure in PADs. [Display omitted]
ISSN:0006-4971
1528-0020
DOI:10.1182/blood.2019001705