Conditional Autoantibodies in Urticaria Patients: A Unifying Hypothesis

Abstract

Chronic urticaria may be characterized by conditional autoantibodies against the alpha-chain of the high-affinity receptor for IgE (FcepsilonRI). These autoantibodies are termed conditional as they only recognize unoccupied FcepsilonRI. The same conditional reactivity pattern has also been found in sera of atopic and normal healthy donors. Any condition resulting in accessibility of FcepsilonRI will render these autoantibodies anaphylactogenic. This finding offers a unifying hypothesis for the manifestation of different forms of urticaria. Non-immunologic triggers may thereby influence directly or indirectly the number of accessible FcepsilonRI allowing the conditional autoantibodies to induce urticaria symptoms.

Natural anti-FcεRIα autoantibodies may interfere with diagnostic tests for autoimmune urticaria

“…Such assays do not account for the fact that urticaria most often appears on the skin as a local phenomenon and thus a serological profile may not be a true indicator of the in vivo pathology. Thus, local disturbances in the homeostatic balance between receptor and ligand might allow natural anti-FcεRI autoAbs access to the FcεRI resulting in a pathogenic interaction accompanied by a local release of mediators [57]. It is not known how many receptors need to be crosslinked to induce mediator release, maybe because the amount depends also on the affinity of the ligand [58].…”

Management of chronic urticaria in Asia: 2010 AADV consensus guidelines

“…These auto-antibodies are termed conditional as they only recognize unoccupied FcεRI [15]. The same conditional reactivity pattern has also been found in sera of atopic and normal healthy donors.…”

A review of recent journal highlights

“…10 The authors have proposed that a state of Ôconditional autoimmunityÕ may exist by which these autoantibodies only become functional when IgE is removed from its receptor, perhaps due to local conditions of urticaria in the skin. 11 In a very recent paper from this group, there was no apparent correlation between anti-FcRI or anti-IgE as detected on sandwich ELISA or basophil histamine release and the ASST response in COU patients. 12 Controversy concerning the usefulness of the ASST in defining groups of patients for clinical and research purposes and the role of autoantibodies seems set to continue.…”

“…Not, at any rate, until a more sensitive ELISA showed that natural anti‐FcεRI autoantibodies are present in low concentrations in healthy subjects and intravenous immunoglobulin preparations 10 . The authors have proposed that a state of ‘conditional autoimmunity’ may exist by which these autoantibodies only become functional when IgE is removed from its receptor, perhaps due to local conditions of urticaria in the skin 11 . In a very recent paper from this group, there was no apparent correlation between anti‐FcεRI or anti‐IgE as detected on sandwich ELISA or basophil histamine release and the ASST response in COU patients 12 .…”