http://www.nejm.org/doi/full/10.1056/NEJM199306033282204
Michihiro Hide, David M. Francis, Clive Grattan, John Hakimi, Jarema P. Kochan, and Malcolm W. Greaves
N Engl J Med 1993; 328:1599-1604June 3, 1993DOI: 10.1056/NEJM199306033282204
Background
Most urticarias are induced by vasoactive mediators such as histamine released from mast cells. Although mast cells are activated by allergens through cross-linking of cell-surface-bound IgE, this mechanism does not appear to explain most cases of chronic urticaria, which, when allergic, infectious, drug-induced, or physical causes cannot be identified, are classified as idiopathic.
Mastopedia Research Feed 
Histamine-releasing IgG autoantibodies against the α subunit of the high-affinity IgE receptor are present in the circulation of some patients with chronic urticaria. Autoantibody-induced cross-linking of IgE receptors may be an important mechanism in the pathogenesis of chronic urticaria and other diseases mediated by mast cells.Hard to overstate the importance of this seminal article. “Histamine-releasing IgG autoantibodies against the α subunit of the high-affinity IgE receptor are present in the circulation of some patients with chronic urticaria. Autoantibody-induced cross-linking of IgE receptors may be an important mechanism in the pathogenesis of chronic urticaria and other diseases mediated by mast cells.” Dr. Asero and Milan colleagues have led the way in following up–finding this mechanism indeed can underlie other MCDs. Xolair is understood to be helpful in many asthma/CU cases with “Hyper-IgE”, but also many cases without such elevations. Jackie Vaughn of the ICUS pointed me to this article’s importance and that over a decade had seemingly passed w/out follow-up w/ SMCDs. We pressed the NIH, TMS in vain. Later, Dr. Asero and his Milan colleagues prolifically stepped up, productively followed up. I understand this to be a basis to administer immunosuppressants in severe, otherwise intractable CU/Angioedema–as the WAO and other authorities recommend. The same basis, I believe, why Drs. Greenberger, Castells at Harvard/Brigham, agreed and got insurance coverage ~ 2006 to administer Xolair off-label for my “MCAS.” This before the FDA had approved Xolair even for urticaria. Unfortunately I could not tolerate Xolair. A brutal blow.