Zillikens D, Ambach A, Zentner A, Dummer R, Schüssler M, Burg G, Bröcker E B
Department of Dermatology, University of Würzburg, Germany.
Br J Dermatol. 1993 Jun;128(6):636-43. doi: 10.1111/j.1365-2133.1993.tb00259.x.
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.
天疱疮是一种自身免疫性水疱病，其中自身抗体已被明确证明具有致病性。由于在未受累皮肤中也发现了自身抗体，因此其他机制可能在天疱疮皮损的发生发展中起重要作用。除了粒细胞外，单核细胞也常见于天疱疮皮损中。为了阐明单核细胞在该疾病病理中的作用，我们测定了天疱疮患者治疗前水疱液和血清样本中可溶性白细胞介素-2受体的水平。白细胞介素-2受体（IL-2R）在活化的单核细胞上表达。根据其合成速率，一部分以可溶性形式（sIL-2R）从细胞表面释放。水疱液中sIL-2R水平为2186±288 U/ml（±标准差），显著高于同期获得的血清样本水平（1299±165 U/ml；P<0.001）。在志愿者的抽吸疱、二度烧伤患者或摩擦性水疱患者中，水疱液和血清中的sIL-2R水平均正常。在天疱疮患者中，全身治疗期间sIL-2R血清水平持续下降，与疾病活动度相关。免疫组织学研究表明，与皮损周围皮肤相比，皮损皮肤的表皮和真皮中IL-2R+细胞显著增加。在真皮中，CD3+T细胞占主导，而在表皮中单核细胞/巨噬细胞最为常见。在寻常型天疱疮中，单核细胞/巨噬细胞局限于基底角质形成细胞，而在落叶型天疱疮中，它们遍布皮损表皮。我们的数据表明，活化的单核细胞存在于天疱疮患者的皮损皮肤中，并可能促成该疾病的病理过程。
