Autoimmune urticaria: chronic relapsing urticaria by autoreactive antibodies

Autoantibodies to the constant region of immunoglobulin E (IgE) or the alpha -chain of the high affinity IgE receptor (Fc epsilon RI) have been demonstrated in 20% to 40% of patients with chronic urticaria (CU). Due to possible continuous stimulation of mediator-containing effector cells (basophils, mastcells), these autoantibodies have established the concept of an autoimmune urticaria (AIU). Intracutaneous injection of autologous serum induces a weal and flare response, preferentially in subjects with chronic idiopathic urticaria. However, autoantibodies of the IgG type to Fc epsilon RI alpha have been demonstrated only in some of these sera utilizing other methods (Westernblot, ELISA technique). Furthermore, immunologically reactive IgG antibodies might fail in activating basophils and inducing mediator production and release (histamine, sulfido leukotrienes) via aggregation of cell-bound high affinity IgE receptors, representing a frequently used surrogate in vitro test for indirect demonstration of functional autoantibody activity. The additional capacitiy of these autoantibodies to trigger the complement cascade (C3a, C5a) might play an amplifying role in activating mediator-containing cells. Subjects demonstrating functional anaphylactogenic anti-Fc epsilon RI alpha antibody activity are more likely to present with severe symptoms. Histology of hives and their cellular infiltrate from AIU patients is not remarkably different from other types of CU. Considering the small number of unoccupied high-affinity IgE receptors, it is not yet clear how anti-Fc epsilon RI alpha antibodies facilitate continuous or episodic mediator release preferentially from cutaneous mastcells. Since other findings implicate the existence of anti-Fc epsilon RI alpha -autoantibodies even in healthy subjects as part of the naturally occurring autoantibody repertoire and possible precursors of tetanus-toxoid antibodies upon affinity maturation, the pathogenetic role and functional relevance of anti-Fc epsilon RI alpha -antibodies in CU remain to be confirmed by further, well controlled studies.