Basophils activation profile and evidence of histamine release factor in Chronic Idiopathic Urticaria / Perfil de ativação de basófilos e evidência de fatores liberadores de histamina na urticária crônica idiopática

AUTOR(ES)

Francinelson Duarte Lourenço

DATA DE PUBLICAÇÃO

2009

RESUMO

INTRODUCTION: Chronic Urticaria is characterized by recurrent, transitory, pruritic and erythematous wheals present for at least six weeks. In most patients the cause is unknown, defined as idiopathic (CIU), however, a sub-group has autoantibodies against the alfa chain of the high affinity IgE receptor (FceRIa) expressed on mast cells and basophils surface making it the target cells in this disease. OBJECTIVES: To evaluate in CIU patients, undergone autologous serum skin test (ASST), the activation profile of the basophils assessed by the expression of activation/degranulation markers and by the ability to release histamine in response to IL-3 priming and cross-linking with anti-IgE antibodies. Furthermore, the presence of histamine releasing factor in sera of patients was evaluated. METHODS: CIU patients (n = 37) were selected from the Dermatological Outpatient Clinic of the Hospital das Clínicas de São Paulo (HC-FMUSP) and submitted to the ASST. The control group consisted of healthy subjects (n=38). The analysis of the expression of FceRI, CD63, CD123 and CD203c on basophils from peripheral blood was assessed by flow cytometry. For the in vitro stimulation with anti-IgE antibodies, the cells were previously primed with human recombinant IL-3. The histamine release assay mediated by sera from patients with CIU was performed with three different donors of leukocytes and released histamine measured by competition ELISA. RESULTS: There is a low number of basophils in peripheral blood of patients with CIU, reflecting a low serum levels of histamine. The scarce basophils in peripheral blood show high expression of FceRI and an up-regulation of CD203c and CD63 marker expression, independently of the ASST. The functional analysis of basophils, revealed that recombinant IL-3 per se induces a significant increase in CD203c expression and the histamine release from basophils of patients with CIU, which are enhanced followed for 15 and 40 minutes of anti-IgE estimulation. The expression of CD63 in basophils upon anti-IgE stimulation, increased only in basophils of healthy individuals, since the baseline levels of CD63 expression on basophils of patients was already up-regulated. The presence of histamine release factors was examined in sera from CIU patients. Three independent experiments were performed, showing the occurrence of 17% of positivity. CONCLUSION: The results show that in CIU, the basophils are primed in vivo due to factor other than autoantibodies anti-FceRI and they have an hyperactive status to the immunological stimuli. The presence of serum histamine releasing factors, independent of the ASST, emphasizes that the intradermal test is suggestive of autorreactivity and not for autoimmunity in UC

ASSUNTO(S)

histamine basophils chronic idiopathic urticaria/immunology autoanticorpos anti-receptor de ige basófilos autologous serum skin test teste intradérmico de soro autólogo autoantibody anti-ige receptor cd203c histamina urticária crônica idiopática/imunologia cd203c

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