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

It is important to note that intestinal hyperpermeability is not necessarily a prerequisite for penetration of food antigens into the lamina propria and systemic circulation. Kleinman and Walker mention that small, nutritionally insignificant amounts of antigenically intact macromolecules may be transferred across the gut lining through simple mechanisms. (44) With this in mind, when we consider the absorption of pounds of foods on a daily basis, continuous exposure between food antigen, most often of the foods eaten regularly, and stimulation of intestinal lymphoid follicles, may very well provide the impetus for the development of a systemic immune response with circulating antibody complexes and atopic reactions.

In Type III, immune complex-mediated hypersensitivity, IgG antibodies combine with food antigen forming circulating immune complexes to which complement is fixed. These immunocomplexes may circulate throughout the periphery and deposit in various tissues promoting an Arthus-like inflammatory reaction with vasculitis and tissue damage. Intestinal biopsy studies have shown evidence of this type of immune-mediated reaction in the pathogenesis of cow's milk sensitive colitis. (45) In another study, Lee et al. have demonstrated deposition of human

IgG and precipitins to cow's milk in lung tissue specimens of infants with pulmonary hemosiderosis. Immunofluorescence of snap-frozen biopsy tissue in these infants exceeded that in control lung biopsies. The researchers suggest a Type III mediated mechanism to explain the presence of the milk-related pulmonary infiltrates. Absorption of the milk antigens through the intestine with subsequent deposition of the circulating immune complexes could not be discounted as there was no evidence to suggest aspiration, and symptoms appeared within the hour following consumption of cow's milk with notable immune complexes appearing in the serum. (46)

Since immunocomplexes, through Type III hypersensitivity are free in circulation, the implications of multiple end organ pathology are not without possible justifications. It may be possible to correlate such phenomena to the pathogenesis and etiology of certain autoimmune disease, (47) connective tissue disorders, and perhaps malignancy.

In addition to IgG involvement in Type I and III hypersensitivity reactions, there are concrete studies demonstrating the role of specific IgG antibodies to food allergens in Type II immune mechanisms as well. In Type II, antibody-dependent cytotoxic hypersensitivity, specific IgG recognize and bind to food antigens that have adhered to the surface of cells. Antigen-antibody bound complex activates the complement cascade and the release of cytotoxic substances from activated killer cells, with eventual cell death. Cow's milk-induced thrombocytopenia has been implicated by this type of reaction. (48)

Through Type IV, cell-mediated delayed hypersensitivity, IgG antibody activity plays an integral role in this type of immune response as well Type IV mechanisms represent a major immunological pathway in conditions such as cow's milk-induced enteropathy and celiac disease. (49) Food induced gastro-enteropathy, specifically celiac disease, has been clearly defined through Type IV mechanisms with the involvement of IgG specific antibodies to wheat gliadin. In this condition, abnormalities in intestinal permeability are associated with both inflammatory processes and loss of jejunal microvilli favoring the absorption of large molecules that pose an allergenic threat. Kemeny et al. have demonstrated increased IgG1 antibody levels to gliadin, ovalbumin, and casein in addition to elevated IgG4 to casein in untreated celiac patients compared to healthy control subjects. (50) In addition, in immediate-type egg allergic patients, these investigators found raised IgG1 antibody levels to ovalbumin, compared to healthy control subjects. (51) In the celiac subjects, in particular, both IgG1 and IgG4 antibody levels to gluten fell with a gluten-free diet.