B: Pharmacological and Nutritional Treatments to Improve Inflammatory IgG Fc Glycosylation
Background. Patients with inflammatory autoimmune diseases often begin to express IgG autoantibodies (autoAbs) years before they develop overt clinical disease. In addition, healthy individuals can express IgG autoAbs in the absence of disease symptoms. There is a correlation between the switch of the autoantigen-specific and total blood IgG Fc glycosylation pattern to more non-galactosylated forms prior to the development of inflammatory autoimmune diseases. Accordingly, non-galactosylated IgG Abs have been associated with inflammatory functions, whereas galactosylated plus terminal sialylated IgG Abs have less inflammatory or anti-inflammatory properties. Furthermore, in models of SLE and epidermolysis bullosa acquisita (EBA), we showed that only those IgG autoAb-positive mice that "switched" to more agalactosylated IgG autoAbs became sick. In addition, the level of total IgG galactosylation and sialylation in the blood is a biomarker of an individual's biological age. Accordingly, a healthy diet may increase the level of total blood IgG galactosylation and sialylation, thereby decreasing biological age.
Objectives. (i) To study the influence of different Biologica (blocking of inflammatory cytokines) on IgG galactosylation and sialylation and inflammatory (auto)immune conditions in mice and humans and their influence on vaccination against pathogens in corresponding patients. (ii) Explore the potential of selected nutrients to increase total blood IgG galactosylation and sialylation to ameliorate inflammatory (auto)immune conditions and the biological age in mice and humans.
Work program. We will treat mice prophylactically or therapeutically with different blocking/therapeutic Abs or selected nutrients in the drinking water to study IgG glycosylation, T and B cell responses and inflammatory (auto)immune conditions. Furthermore, we will analyze the effects of biologics and diets in patients with inflammatory (auto)immune conditions on IgG glycosylation, T and B cell responses and disease severity, as well as the influence of such treatments on immune responses after vaccination of these patients.
- Projects
- 1st Generation
- 2nd Generation
- A: Defining Autoimmune Pre-Disease
- B: Targeting of Autoimmune Pre-Disease
- B: Pharmacological and Nutritional Treatments to Improve Inflammatory IgG Fc Glycosylation
- MD projects