The architecture of the IgG anti-carbohydrate repertoire in primary antibody deficiencies (PADs).

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 IgG exhibits modular organization related to glycan epitope structure. The current study compares the glycan-specific IgG repertoires among different PAD entities. Distinct repertoire profiles with extensive qualitative glycan-recognition defects were observed, characterized by the common loss of Gala- and GalNAc-reactivity and disease-specific recognition of microbial, self-antigens and tumor-associated carbohydrate antigens. Antibody repertoire analysis may provide a useful tool to elucidate the dimension and clinical implications of the immune system failure in individual patients.