Up-regulated perforin expression of CD8+ blood lymphocytes in generalized non-anaphylactic drug eruptions and...

Perforin expressed in CD8+ cytotoxic T cells is known to mediate the lysis of target cells carrying microbial as well as tumor-associated antigens, and to be involved in autoimmune and transplant reactions. The aim of the present investigation was to study the role of perforin- and CD8-expressing effector lymphocytes from peripheral blood in patients with generalized inflammatory skin diseases. Mononuclear cells were separated from peripheral venous blood and permeabilized by 0.1% saponin. The co-expression of cytoplasmatic perforin and cell membrane-residing CD8 was determined in lymphocytes by immuno-flow cytometry. Patients affected by generalized macular-papular drug eruptions (n = 14), drug-unrelated acute urticaria (n = 10) and drug-independently exacerbated psoriasis (n = 11, PASI scores ranging from 25 to 35), as well as control individuals not affected by any inflammatory skin disease (n = 10) were enrolled. Additionally, n = 5 patients with drug-induced Stevens-Johnson syndrome (SJS) were included. The average proportion of CD8+ peripheral lymphocytes co-expressing perforin in generalized drug eruptions (68.8+/-24.9%) and exacerbated psoriasis (67.2+/-17.1%) differed significantly from the controls (43.5+/-11.6%; p 0. 05), whereas no significant difference for acute urticaria (58.2+/-23.1%) could be measured. In each of the 5 SJS patients treated by high dose systemic steroids the parameter substantially declined during the first 7 days after admission from an average value of 81. 6% down to 33.0%. Thus, as compared to controls we observed an increased perforin+ proportion of CD8+ lymphocytes in generalized drug eruptions and in exacerbated psoriasis but not in acute urticaria. Therefore the parameter showed some specificity as a marker of distinct inflammatory skin disorders, and proved to be useful in monitoring the disease activity of SJS under anti-inflammatory medication. Furthermore, the findings point to a possible crucial role of CD8+ lymphocytes in the pathogenesis of psoriasis.