Classification of anti-FcepsilonRI and anti-IgE autoantibodies in chronic idiopathic urticaria and correlation with disease severity.
BACKGROUND
Circulating autoantibodies against FcepsilonRI, IgE, or both occur in approximately one third of patients with chronic idiopathic urticaria (CIU), but not all autoantibodies initiate histamine release.


OBJECTIVE
We sought to classify patients with CIU into subsets on the basis of serum bioactivity and immunoreactivity and to examine the relationship between newly defined subtype and disease severity.


METHODS
Sera from patients with CIU (n = 78), dermog-raphism (n = 15), and cholinergic urticaria (n = 10) and sera from healthy subjects (n = 39) were analyzed by means of Western blot analysis for anti-FcepsilonRI autoantibodies and for histamine release from basophils and dermal mast cells. In vivo reactivity of autologous serum was tested by means of intradermal injection, and CIU severity was determined on the basis of clinical interview.


RESULTS
We classified sera from patients with CIU into 5 subsets: immunoreactive histamine-releasing anti-FcepsilonRI autoantibodies (n = 20 [26%]); immunoreactive anti-FcepsilonRI autoantibodies without histamine-releasing activity (n = 12 [15%]); anti-IgE-like autoantibodies (n = 7 [9%]); serum containing a mast cell-specific histamine-releasing factor (n = 7 [9%]); and sera with no identifiable factor (n = 32 [41%]). Patients with serum histamine-releasing activity had more severe urticaria than patients without such activity. Positive skin test responses to autologous sera were associated with histamine-releasing anti-FcepsilonRI autoantibodies but not with non-histamine-releasing anti-FcepsilonRI autoantibodies. Neither healthy subjects nor patients with dermographism or cholinergic urticaria had his-tamine-releasing anti-FcepsilonRI autoantibodies.


CONCLUSIONS
These data support the specificity of functional anti-FcepsilonRI autoantibodies to CIU. The identification of distinctive subsets of patients suggests that other pathogenic mechanisms occur in CIU in addition to direct ligation of FcepsilonRI by autoantibodies causing dermal mast cell degranulation. Elucidating these mechanisms might lead to new treatments for CIU.
St John's Institute of Dermatology and the Department of Obstetrics and Gynaecology, Guy's, King's and St Thomas' School of Medicine, King's College London, St Thomas' Hospital, London.
Ruth A
RA
Sabroe
Edda
E
Fiebiger
David M
DM
Francis
Dieter
D
Maurer
Paul T
PT
Seed
Clive E h
CE
Grattan
Anne Kobza
AK
Black
Georg
G
Stingl
Malcolm W
MW
Greaves
Robert M
RM
Barr
D000293:Adolescent; D000328:Adult; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D015153:Blotting, Western; D002908:Chronic Disease; D006636:Histamine Release; D006801:Humans; D008875:Middle Aged; D017455:Receptors, IgE / Q000276:immunology*; D012882:Skin Tests; D014581:Urticaria / Q000145:classification* / Q000175:diagnosis* / Q000276:immunology
D000888:Antibodies, Anti-Idiotypic; D001323:Autoantibodies; D017455:Receptors, IgE; C026408:anti-IgE antibodies