自身免疫性副肿瘤性天疱疮发病机制的研究进展

副肿瘤性天疱疮(paraneoplastic pemphigus,PNP)是由Anhalt等[1,2]于1990年命名的一种自身免疫性皮肤黏膜疾病,该病特点为伴发肿瘤及血清中存在能识别表皮蛋白成分的独特的IgG自身抗体.我科自1999年诊断了我国首例PNP患者后[3],至今已收治了12例.本文就我科所见PNP结合文献对临床特点作一介绍,并重点探讨其发病机制.

The new development on pathogenesis of autoimmune paraneoplastic pemphigus

Paraneoplastic pemphigus (PNP) is an autoimmune mucocutaneous disease first named by Anhalt, et al. in 1990. The disease is characterized by such distinctive clinical symptoms and signs as severe, painful mucosal erosions, polymorphous skin lesions, histopathology hallmarks, and immunological findings. The situation typically presents in patients with lymphoproliferative diseases and primarily malignancies. A main challenge of the study is the relationship between the existence of associated tumors and the autoimmune reaction to the skin. Some researchers suspected that the possible expression of foreign antigens on the tumor can cross react with epidermal antigens inducing the auto-reactive clones of T-lymphocytes. Some speculated that the type of tumors associated with PNP may produce plakin proteins that result in initiation of the immune response. Other reports believed the autoimmune reaction is related to the epitope spreading or to the changing of cytokines. We analyzed 12 PNP patients diagnosed in our department in the past few years. An intensive study to the B cells in the PNP associated with tumors demonstrated that the tumors have structural basis to produce antibody. The similar immunoglobulin heavy chain genes of tumor B-cells in 7 patients strongly suggested that the B cell clones were functional and recognized the same antigen epitope. The autoantibodies secreted by the tumor can react against specific plakin proteins in epidermis, lead to the impairment of cell-cell adhesion, and cause the mucocutanous lesions. The clinical significance of the results indicates the importances of early finding and total resection of the associated tumors, and the usage of IVIG pre or during operation to prevent Bronchitis Obliterans. The new finding is also important for the study of other antibody mediated autoimmune diseases.