Autoimmune urticaria: chronic relapsing urticaria by autoreactive antibodies

Autoantibodies to the constant region of immunoglobulin E (IgE) or the alph a -chain of the high affinity IgE receptor (Fc epsilon RI) have been demons trated in 20% to 40% of patients with chronic urticaria (CU). Due to possib le continuous stimulation of mediator-containing effector cells (basophils, mastcells), these autoantibodies have established the concept of an autoim mune urticaria (AIU). Intracutaneous injection of autologous serum induces a weal and flare response, preferentially in subjects with chronic idiopath ic urticaria. However, autoantibodies of the IgG type to Fc epsilon RI alph a 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 product ion and release (histamine, sulfido leukotrienes) via aggregation of cell-b ound high affinity IgE receptors, representing a frequently used surrogate in vitro test for indirect demonstration of functional autoantibody activit y. The additional capacitiy of these autoantibodies to trigger the compleme nt cascade (C3a, C5a) might play an amplifying role in activating mediator- containing cells. Subjects demonstrating functional anaphylactogenic anti-F c epsilon RI alpha antibody activity are more likely to present with severe symptoms. Histology of hives and their cellular infiltrate from AIU patien ts is not remarkably different from other types of CU. Considering the smal l number of unoccupied high-affinity IgE receptors, it is not yet clear how anti-Fc epsilon RI alpha antibodies facilitate continuous or episodic medi ator 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 repertoir e and possible precursors of tetanus-toxoid antibodies upon affinity matura tion, the pathogenetic role and functional relevance of anti-Fc epsilon RI alpha -antibodies in CU remain to be confirmed by further, well controlled studies.