AUTOANTIBODIES AGAINST THE HIGH-AFFINITY IGE RECEPTOR AS A CAUSE OF HISTAMINE-RELEASE IN CHRONIC URTICARIA

被引:716
作者
HIDE, M
FRANCIS, DM
GRATTAN, CEH
HAKIMI, J
KOCHAN, JP
GREAVES, MW
机构
[1] HOFFMANN LA ROCHE INC,DEPT MOLEC GENET,NUTLEY,NJ 07110
[2] HOFFMANN LA ROCHE INC,DEPT IMMUNOPHARMACOL,NUTLEY,NJ 07110
关键词
D O I
10.1056/NEJM199306033282204
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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. Methods. We recruited 26 patients with chronic idiopathic urticaria, in whom intradermal injection of autologous serum caused a wheal-and-flare response. Serum from four patients that induced marked histamine release from basophils from a donor with very low serum IgE levels was studied with respect to the IgE dependence of the histamine release, the activity of the IgG fractions, and the neutralizing effect of a recombinant preparation of the soluble extracellular domain of the a subunit of the high-affinity IgE receptor (sFcepsilonRIalpha). Results. The histamine-releasing activity of the serum was abolished by passive sensitization of basophils with myeloma IgE, enhanced after dissociation of IgE by treatment with lactic acid, and induced by IgG fractions from the serum of all four patients. Preincubation of the serum and isolated IgG with sFcepsilonRIalpha resulted in almost complete neutralization. Conclusions. Histamine-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 receptors may be an important mechanism in the pathogenesis of chronic urticaria and other diseases mediated by mast cells.
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页码:1599 / 1604
页数:6
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共 28 条
[1]   GENETIC AND MUTATIONAL ANALYSIS OF THE T-CELL ANTIGEN RECEPTOR [J].
ASHWELL, JD ;
KLAUSNER, RD .
ANNUAL REVIEW OF IMMUNOLOGY, 1990, 8 :139-167
[2]  
BAMEZAI A, 1989, J IMMUNOL, V143, P3107
[3]   AUTOANTIBODIES TO CYTOKINES - FRIENDS OR FOES [J].
BENDTZEN, K ;
SVENSON, M ;
JONSSON, V ;
HIPPE, E .
IMMUNOLOGY TODAY, 1990, 11 (05) :167-169
[4]  
BLANK U, 1991, J BIOL CHEM, V266, P2639
[5]   IGM ANTI-FC-GAMMA-R AUTOANTIBODIES TRIGGER NEUTROPHIL DEGRANULATION [J].
BOROS, P ;
ODIN, JA ;
MURYOI, T ;
MASUR, SK ;
BONA, C ;
UNKELESS, JC .
JOURNAL OF EXPERIMENTAL MEDICINE, 1991, 173 (06) :1473-1482
[6]   A PRACTICAL APPROACH TO THE URTICARIAL SYNDROMES - A DERMATOLOGISTS VIEW [J].
CHAMPION, RH .
CLINICAL AND EXPERIMENTAL ALLERGY, 1990, 20 (02) :221-224
[7]  
ENGELMANN H, 1990, J BIOL CHEM, V265, P14497
[8]   A SEROLOGICAL MEDIATOR IN CHRONIC IDIOPATHIC URTICARIA - A CLINICAL, IMMUNOLOGICAL AND HISTOLOGICAL-EVALUATION [J].
GRATTAN, CEH ;
WALLINGTON, TB ;
WARIN, RP ;
KENNEDY, CTC ;
BRADFIELD, JW .
BRITISH JOURNAL OF DERMATOLOGY, 1986, 114 (05) :583-590
[9]   THE PATHOLOGY OF THE AUTOLOGOUS SERUM SKIN-TEST RESPONSE IN CHRONIC URTICARIA RESEMBLES IGE-MEDIATED LATE-PHASE REACTIONS [J].
GRATTAN, CEH ;
BOON, AP ;
EADY, RAJ ;
WINKELMANN, RK .
INTERNATIONAL ARCHIVES OF ALLERGY AND APPLIED IMMUNOLOGY, 1990, 93 (2-3) :198-204
[10]   DETECTION OF CIRCULATING HISTAMINE RELEASING AUTOANTIBODIES WITH FUNCTIONAL-PROPERTIES OF ANTI-IGE IN CHRONIC URTICARIA [J].
GRATTAN, CEH ;
FRANCIS, DM ;
HIDE, M ;
GREAVES, MW .
CLINICAL AND EXPERIMENTAL ALLERGY, 1991, 21 (06) :695-704