M. Hide et al., AUTOANTIBODIES AGAINST THE HIGH-AFFINITY IGE RECEPTOR AS A CAUSE OF HISTAMINE-RELEASE IN CHRONIC URTICARIA, The New England journal of medicine, 328(22), 1993, pp. 1599-1604
Background. Most urticarias are induced by vasoactive mediators such a
s histamine released from mast cells. Although mast cells are activate
d by allergens through cross-linking of cell-surface-bound IgE, this m
echanism does not appear to explain most cases of chronic urticaria, w
hich, when allergic, infectious, drug-induced, or physical causes cann
ot be identified, are classified as idiopathic. Methods. We recruited
26 patients with chronic idiopathic urticaria, in whom intradermal inj
ection of autologous serum caused a wheal-and-flare response. Serum fr
om four patients that induced marked histamine release from basophils
from a donor with very low serum IgE levels was studied with respect t
o the IgE dependence of the histamine release, the activity of the IgG
fractions, and the neutralizing effect of a recombinant preparation o
f the soluble extracellular domain of the a subunit of the high-affini
ty IgE receptor (sFcepsilonRIalpha). Results. The histamine-releasing
activity of the serum was abolished by passive sensitization of basoph
ils with myeloma IgE, enhanced after dissociation of IgE by treatment
with lactic acid, and induced by IgG fractions from the serum of all f
our patients. Preincubation of the serum and isolated IgG with sFcepsi
lonRIalpha resulted in almost complete neutralization. Conclusions. Hi
stamine-releasing IgG autoantibodies against the a subunit of the high
-affinity IgE receptor are present in the circulation of some patients
with chronic urticaria. Autoantibody-induced cross-linking of IgE rec
eptors may be an important mechanism in the pathogenesis of chronic ur
ticaria and other diseases mediated by mast cells.