IgE and IgE Receptors in ‘Allergic’ Skin Diseases
The Role of the IgE Receptor in Chronic Autoimmune Urticaria
Malcolm W Greaves
St Thomas' Hospital
London, United Kingdom
In 1993 we demonstrated that serum of a subset of patients with chronic "idiopathic" urticaria (CIU) contained IgG autoantibodies directed against the α - chain of FcεR1, or, less commonly, against IgE. These antibodies are functional, for example releasing histamine from basophils and dermal mast cells in vitro and causing whealing upon intradermal injection in vivo. Subsequently these results have, in essence, been reproduced by many investigators worldwide. Furthermore, removal or suppression of these antibodies by means of immunomodulatory therapies has been shown to bring about relief of symptoms, sometimes sustained, in selected patients with recalcitrant disease.
However a number of problems remain unsolved:
The cause of hives in around 50% of patients with CIU who don`t have detectable autoantibodies remains unclear. Insensitivity of available tests for autoantibodies seems an unlikely cause. Other possibilities include the presence of an, as yet, incompletely characterised serum "mast cell specific factor" described by us in 1996, and a recently reported defective p21 signaling pathway in some CIU patients.
Contrary to our original findings, complement appears to be involved in at least some patients with autoimmune urticaria.
Why do serum immunoreactive anti - FcεR1 autoantibodies fail to release histamine in some CIU patients (ie appear to be non – functional)? One possibility is that they may be bi – specific in some patients ie co – aggregate FcεR1 and FcγR 11B, causing inhibition of release.
The specificity of anti - FcεR1 autoantibodies in CIU has been questioned by one European group, although their findings have yet to be reproduced independently.
Diagnosis of autoimmune urticaria remains problematic; the autologous serum skin test is useful but of limited sensitivity and specificity, but other screening tests are being sought. In vitro, immunoassays have proved disappointing and at present the release of histamine or other indicators from target basophils or mast cells remains the gold standard for confirmation of autoimmune urticaria.
There seems no doubt that hives are caused by autoantibodies against the high affinity IgE receptor in some patients with CIU. However the search for additional pathomechanisms in other patients must continue.