Please consider the following as to why there may not have be as many IgG4/C3D sensitivities:
- Total IgG vs IgG4: The distribution of IgG subclasses can vary depending on factors such as age, health status, and exposure to specific antigens Of the five immunoglobulin isotypes, immunoglobulin G (IgG) is most abundant in human serum. The four subclasses are: IgG1, IgG2, IgG3, and IgG4 [ref]. Among these subclasses, IgG1, IgG2, and IgG3 are typically more abundant than IgG4. IgG4 is the least common subclass, constituting a smaller proportion of the total IgG antibodies. Thus, having multiple IgG4 sensitivities is not as common compared to IgG/IgA.
- Missing C3D activators: The C3d complement pathway is a component of the complement system, which is a part of the immune system that enhances the ability of antibodies and phagocytic cells to clear pathogens from an organism. A self-antigen recognized by a natural antibody (i.e., autoimmunity) provides a chance for the initiation of the classical complement pathway, resulting in the deposition of C3d on the antigen (Mak & Saunders, 2006). Additionally, when food antigens are decreased as a result of an exclusion diet, a decrease in C3d/IgG food sensitivities can be seen (Clarke et. al, 2015). Thus, if the food antigen is not present because it is not eaten as often or no autoimmune response is prompted, the C3D pathway is less likely to be activated.
- Multiple downstream effects: While intestinal permeability may contribute to food sensitivities (which we have established is more likely to present with IgG/IgA antibodies than IgG4/C3d responses, unless the complement system is activated), perhaps leaky gut is manifesting itself in other areas.
The leakage in leaky gut may be responsible for a huge variety of health issues, ranging from minor (bloating, cramps, fatigue, food allergies and sensitivities, gas, and headaches) to “bigger things”: autoimmune conditions, depression and other mood disorders, diabetes, inflammatory bowel disease, and multiple sclerosis” (Camilleri, 2019).
