Functional and clinical consequences of Fc receptor polymorphic and copy number variants

Receptors for immunoglobulins (Fc receptors) play a central role during an immune response, as they mediate the specific recognition of antigens of almost infinite diversity by leucocytes, thereby linking the humoral and cellular components of immunity. Indeed, engagement of Fc receptors by immunoglobulins initiates a range of immunoregulatory processes that might also play a role in disease pathogenesis. In the circulation, five main types of immunoglobulins (Ig) exist - namely IgG, IgA, IgE, IgM and IgD and receptors with the ability to recognize and bind to IgG (Fc gamma receptor family), IgE (Fc epsilon RI and CD23), IgA (CD89; Fc alpha/mu R) and IgM (Fc alpha/mu R) have been identified and characterized. However, it is astonishing that nearly all the known human Fc receptors display extensive genetic variation with clear implications for their function, thus representing a substantial genetic risk factor for the pathogenesis of a range of chronic inflammatory disorders.