Classification of anti-FcepsilonRI and anti-IgE autoantibodies in chronic idiopathic urticaria and correlation with disease severity.

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.
Journal of Allergy and Clinical Immunology (Impact Factor: 12.05). 10/2002; 110(3):492-9.
Source: PubMed

ABSTRACT 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.
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.
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.
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.
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.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Chronic urticaria (CU) is a widespread skin disease, characterized by the recurrence of transient wheals and itch for more than 6 weeks. Besides autoimmune mechanisms, coagulation factors, in particular tissue factor and thrombin, might also participate in the disease pathophysiology. Tissue factor expressed by eosinophils can induce activation of blood coagulation generating thrombin which in turn can increase vascular permeability both directly, acting on endothelial cells, and indirectly, inducing degranulation of mast cells with release of histamine, as demonstrated in experimental models. D-dimer, a fibrin degradation product, generated following activation of the coagulation cascade and fibrinolysis, has been found to be increased during urticaria exacerbations; moreover, it has been proposed as a biomarker of severity and resistance to H1-antihistamines in CU patients. The possible role of coagulation in CU is also supported by case reports, case series and a small controlled study showing the efficacy of anticoagulant therapy in this disease. The purpose of this review was to summarize the available data on the possible contribution of coagulation to the pathophysiology of CU focusing on clinical aspects and possible future therapeutic developments.
    Allergy 03/2014; · 5.88 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Urticaria is a skin disease that affects approximately 5% of the general population and manifests itself, not only as an acute but also as a chronic disease. The etiology of the disease varies as well as its clinical manifestations which extend from the presence of urticarial hives to the potentially mortal angioedema. There is a great interest to the disease not only due to its special clinical manifestation but also due to its pathogenetic mechanism. New data in the medical bibliography support the participation of interleukins (ILs) in the pathophysiology of urticaria. The aim of the study is to contribute in the comprehension of possible participation of certain ILs in the pathogenesis of acute urticaria. Our study concerns four ILs, IL-4, IL-6, IL-8 and IL-10, simultaneously and their quantitative changes during the acute phase of urticaria as well as 2 weeks after drug administration. Moreover, ILs levels of patients were compared with those of matched healthy controls. All measurements have been done by the ELISA method. The statistical analysis was done by SPSS. The results present increased levels (in 51 patients vs. 22 matched healthy controls) of all four ILs during the acute phase. Especially for IL-4 this increase was statistically very significant (P < 0.001). Statistically marginally significant decrease was also observed for IL-10 concentrations (P < 0.059), for the two blood samples (acute phase and 2 weeks later). It is suggested by the present study that certain ILs might play an important role in the pathogenetic mechanism of urticaria. IL-4 and IL-10 participation seems to be relatively more significant. Possibly, ILs, liberated by mast cells, induce an influx of leukocytes in the dermis, therefore participating in the development of acute urticaria inflammation.
    Journal of Clinical Medicine Research 04/2014; 6(2):133-7.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Chronic spontaneous urticaria (CU) is a common skin disorder, with an estimated prevalence of 0.5-1.8% in most populations. Around 30-50% of CU patients have an autoimmune etiology, with autoantibodies (autoAbs) against IgE, FcεRIα, and FcεRII/CD23. Although the in vivo autologous serum skin test (ASST) and in vitro histamine release/activation assay are the most frequently used screening methods, these two have many limitations and do not directly measure susceptible autoAbs. This study aimed to establish an in vitro rapid screening test using recombinant autoantigen FcεRIα(rFcεRIα) to improve the diagnosis of autoimmune urticaria.
    PLoS ONE 01/2014; 9(10):e109565. · 3.53 Impact Factor


Available from
May 21, 2014