A critical review of IgG immunoglobulins and food allergy—implications in systemic health

Townsend Letter for Doctors and Patients, August-Sept, 2003 by Raymond M. Suen, Shalima Gordon

Like all immune mediated reactions, food allergies depend on the intimate association between mature T-helper cells and B-lymphocytes with the production and release of inflammatory mediators and activation of food-specific antibodies. After B-cells are stimulated by antigen, they are terminally differentiated into plasma cells which secrete antigen-specific immunoglobulins.

A review of T-helper 2 (TH2) and T-helper 1 (TH1)-induced antibody production reminds us that interleukin-2 (IL2), interferon gamma (IFN gamma), and tumor necrosis factor beta (TNF beta), via TH1 T-helper cell activity, favors B-lymphocyte class switching to the production of IgG2a. Conversely, IL-4 and IL-5 secreted by TH2 T-helper cells induce class switching to IgE and IgG1. The exact role of the different subclasses of IgG remains to be understood. Studies suggest sequential switching as a prerequisite for B-cell differentiation, most prominent in cells that switch to IgE. For instance, B-cells cultured with interleukin4 show IgG1/IgE double-positive staining, which appear after 3 days of culture, after which they predominantly secrete IgE on reculture. This serves as an interesting note suggesting an essential switch from IgG1 with possible prerequisite involvement in IgE production. (27) The amount of antigen absorbed, the quantity of antibody required, the chronicity of antigen exposure, and the specific role of IgG subclasses in the pathogenesis of food allergic illness, clearly influence progression of disease, and define the magnitude of the immune response to dietary antigen, warrant further investigation.

A key feature of food allergies that deserves close attention is its implications in the development and maintenance of immune cell memory from chronic and repeated exposure to food allergens, with resultant clinical consequences. Food-induced immune reaction favors maturation and proliferation of naive T-cells into CD4 and CD8 effector T-cell lines. Under chronic antigen exposure CD4 populations generate distinct populations, as mentioned above, TH1 and TH2 of which TH2 promotes the activation of cytokines favoring immunoglobulin production. From chronic antigen exposure there is a pronounced alteration in the ratio between TH1 and TH2, suggesting immune imbalance, polyclonal B-cell activation, and an exaggerated immunoglobuiin response. This mechanism of action has been argued for autoimmune disease due to chronic antigen exposure, and has interesting implications in food allergies, which also represent a state of chronic antigen exposure. As such, the role of IgG in delayed-onset food allergies deserves close attention for its implications in systemic disease.

There is no argument regarding the presence of serum IgG reactive with different dietary proteins. Specific serum IgG antibodies to different food proteins have been reported in significant numbers of adults and children in cases of celiac disease, dermatitis herpetiformis, and atopic eczema. (28,29) Moreover, higher total and specific serum IgG4 levels to common foods are raised in cases of atopic eczema compared to the healthy population. (30,31) The presence of elevated levels of IgG antibodies to food antigens have been observed substantially in diseases with increased intestinal permeability, in particular, IgA deficiency (32) and inflammatory bowel disease. (33)