Marcadores de ativação de linfócitos T e de suas citocinas como ferramentas diagnósticas na hipersensibilidade alérgica a fármacos

Abstract

Drug allergy reactions represent one third of adverse drug reactions, and although they are infrequent, they present high rates of morbidity and mortality, revealing a major public health problem. The main challenges related to drug hypersensitivity result from its unpredictability, no animal model for research and individual variability with regard to drug metabolism. Drug allergy reactions are difficult to be diagnosed once there is a lack of laboratorial tests for their investigation. The present study aimed to establish some immunological in vitro methods for diagnosing drug allergy. Patients (n=20) attending a dermatology outpatient clinic, Hospital Universitario Walter Cantídio, Universidade Federal Ceara, with mucocutaneous and systemic manifestations due to drug hypersensitivity were investigated by clinical history, laboratory findings, and in vivo and in vitro tests. The lymphocyte activation markers, CD25 and CD69, were evaluated by flow cytometry on the peripheral blood mononuclear cells previously incubated with different concentrations of the suspected drug, and analysis of interferon γ and interleukin 5 was done in the culture supernatant by enzyme immunoassay. Eighteen patients were tested by skin tests; nine patients showed positive results to one or more drugs. Fifteen patients showed positivity for at least one of activation markers in response to the suspected drug. The markers CD69 and/or CD25 were expressed by T cells CD4+ and CD8+, both in immediate and delayed reactions. Comparing stimulation index of the markers between patients and healthy no allergic individuals, it was observed a significant difference for CD4+CD69+ in the three suspected drug concentrations and CD4+CD25+ only in the lower drug concentration. No significant differences were found for the cytokines IFN-γ and IL-5 between patients and healthy individuals. The detection of both activation markers CD69 and CD25 increased the diagnostic sensitivity of the test. The use of both markers represents a promising tool in drug allergy diagnosis. Nonetheless, this hypothesis needs to be confirmed with a greater number of patients and controls.