Aoki Valeria, Millikan Robert C, Rivitti Evandro A, Hans-Filho Gunter, Eaton Donald P, Warren Simon J P, Li Ning, Hilario-Vargas Julio, Hoffmann Raymond G, Diaz Luis A
Department of Dermatology, University of Sao Paulo, Sao Paulo, Brazil.
J Investig Dermatol Symp Proc. 2004 Jan;9(1):34-40. doi: 10.1111/j.1087-0024.2004.00833.x.
An ongoing sero-epidemiological study of the Terena reservation of Limao Verde, known to have a high prevalence and incidence of FS, has revealed important information about this autoimmune disease. During surveillance of this population of approximately 1,200, which began in 1994, we documented 43 FS cases and studied the transition from the normal state to the disease state in several of these individuals. Furthermore, we established that FS patients as well as a large number of normal individuals on the reservation possess anti-dsg1 autoantibodies. The following interesting observations were made: (1) the ectodomain of dsg1 contains epitopes recognized by both autoantibodies and T cells from FS patients; (2) pathogenic anti-dsg1 autoantibodies in FS belong to the IgG4 subclass; (3) nonpathogenic anti-dsg1 autoantibodies of the IgG1 subclass were detected in normal individuals from Limao Verde and in patients in the preclinical stage of the disease; (4) anti-dsg1 autoantibodies from normal individuals and patients in the preclinical stage of FS recognize the EC5 domain of dsg1, whereas pathogenic anti-dsg1 autoantibodies bind the EC1/EC2 domains; (5) houses of FS patients are rustic, with thatched roofs and walls and dirt floors; (6) there was a high frequency of hematophagous insects (bedbugs and kissing bugs) in the houses of FS patients; (7) previous studies revealed that the predominant black fly on this reservation belongs to the species Simunlium nigrimanum. These findings suggest that the environmental antigen(s) triggering the autoimmune response in FS may be linked to exposure to hematophagous insects.
对利毛韦尔德的特雷诺保留地进行的一项正在进行的血清流行病学研究显示了有关这种自身免疫性疾病的重要信息，该保留地已知扁平苔藓（FS）的患病率和发病率很高。在对这一约1200人的人群进行监测期间（始于1994年），我们记录了43例FS病例，并研究了其中一些个体从正常状态到患病状态的转变。此外，我们确定FS患者以及该保留地的大量正常个体都拥有抗桥粒芯糖蛋白1（dsg1）自身抗体。得出了以下有趣的观察结果：（1）dsg1的胞外域包含被FS患者的自身抗体和T细胞识别的表位；（2）FS中的致病性抗dsg1自身抗体属于IgG4亚类；（3）在来自利毛韦尔德的正常个体和疾病临床前期患者中检测到IgG1亚类的非致病性抗dsg1自身抗体；（4）来自正常个体和FS临床前期患者的抗dsg1自身抗体识别dsg1的EC5结构域，而致病性抗dsg1自身抗体结合EC1/EC2结构域；（5）FS患者的房屋很简陋，有茅草屋顶、墙壁和泥土地面；（6）FS患者房屋中有大量吸血昆虫（臭虫和锥蝽）；（7）先前的研究表明，该保留地的主要黑蝇属于黑腹蚋物种。这些发现表明，引发FS自身免疫反应的环境抗原可能与接触吸血昆虫有关。
