Evidence for cell-mediated immune mechanisms in the pathology of pemphigus

Pemphigus is an autoimmune blistering disease in which autoantibodies have clearly been shown to be pathogenic. Because autoantibodies are also found in uninvolved skin, further mechanisms may be important in the development of pemphigus lesions. In addition to granulocytes, mononuclear cells are commonly found in pemphigus lesions. To elucidate the role of mononuclear cells in the pathology of this disease, we determined the levels of soluble interleukin-2 receptor in blister fluid and serum samples from pemphigus patients prior to treatment. The interleukin-2 receptor (IL-2R) is expressed on activated mononuclear cells. Depending on its rate of synthesis, a portion is released from the cell surface in a soluble form (sIL-2R). In blister fluid, sIL-2R levels were 2186 ± 288 U/ml (± SD), which was significantly higher than levels in concurrently obtained serum samples (1299 ± 165 U/ml; P < 0.001). In suction blisters in volunteers, and in patients with second-degree burns or friction-induced bullae, sIL-2R levels were normal in both blister fluid and serum. In pemphigus patients, sIL-2R serum levels continuously declined during systemic therapy, correlating with disease activity. Immunohistological studies demonstrated a marked increase in IL-2R⁺ cells in both the epidermis and dermis of lesional skin compared with perilesional skin. In the dermis, CD3⁺ T cells predominated, whereas monocytes/macrophages were most frequent in the epidermis. In pemphigus vulgaris, monocytes/macrophages were restricted to the basal keratinocytes, whereas in pemphigus foliaceus, they were found throughout the lesional epidermis. Our data indicate that activated mononuclear cells are present in lesional skin of pemphigus patients, and may contribute to the pathology of this disease.