Use of multi-parametric flow cytometry to study patterns of immune activation in peripheral blood in patients with drug hypersensitivity reactions

Drug hypersensitivity reactions (DHR) are frequently encountered in clinical practice, and often result in significant morbidity and mortality. Diagnosis of DHR is based upon clinical signs, symptomatology and biochemical parameters, and is frequently complicated by factors including polypharmacy and difficulty excluding conditions mimicking DHR. Currently available laboratory assays employed in the work-up of DHR include evaluation of lymphocytes, basophils and other cell types in peripheral blood specimens after ex-vivo stimulation with the culprit drug in the convalescent phase, several weeks after the initial reaction. There are no robust tests available for diagnosing DHR at the time of the reaction. The ability to diagnose and differentiate between various reaction types during the acute phase would facilitate early identification and specific management of affected patients. Up-regulation of several cell surface activation markers have been described in the context of Type 4 DHR, including CD69 which becomes up-regulated in various cell types, increased expression of CD40L, HLA-DR and CD25 on T cells, and up-regulation of CD107a and cytoplasmic perforin and granzyme in NK and cytotoxic T cells. 1 We present a case-based discussion of patterns of immune activation in the peripheral blood of patients presenting with acute DHR, and describe the differential up-regulation of various cell surface and cytoplasmic markers in different DHR sub-types.