Ooi Joshua D, Holdsworth Stephen R, Kitching A Richard
Monash University Department of Medicine, Monash Medical Centre, Clayton, VIC 3168, Australia.
J Autoimmun. 2008 Nov;31(3):295-300. doi: 10.1016/j.jaut.2008.04.005. Epub 2008 May 27.
Goodpasture's disease, an "organ-specific" autoimmune disease is manifest by rapidly progressive glomerulonephritis and pulmonary hemorrhage. Studies into the pathogenesis of this disease have shed light on the autoantigen (the non-collagenous domain of the alpha3 chain of type IV collagen, alpha3(IV)NC1) and its epitopes, as well as the involvement of autoantibodies and cellular effectors in disease. The discovery of alpha3(IV)NC1 lead to studies that defined the structure and biology of type IV collagen and are defining B and T cell epitopes. Goodpasture autoantibody epitopes are "cryptic" in that they are structurally sequestered by adjacent non-collagenous domains of alpha4 and alpha5 type IV collagen. T cell epitope studies in rats demonstrated that a 13-mer could induce experimental autoimmune glomerulonephritis. T cells from patients with Goodpasture's recognize two epitopes, in regions which are highly susceptible in antigen processing by endosomal proteases. Goodpasture's disease is strongly associated with HLA DRB1 genes, whereby DRB11501 confers susceptibility and the DRB10701 and DRB1*0101 are dominantly protective. Experimental data implicate both autoantibodies and cell mediated immunity as disease effectors. Observations in humans suggest that regulatory T cells are associated with the development of self-immunoregulation in the convalescent phase of disease.
肺出血肾炎综合征是一种“器官特异性”自身免疫性疾病，表现为快速进展性肾小球肾炎和肺出血。对该疾病发病机制的研究揭示了自身抗原（IV型胶原α3链的非胶原结构域，α3(IV)NC1）及其表位，以及自身抗体和细胞效应因子在疾病中的作用。α3(IV)NC1的发现促使了对IV型胶原结构和生物学的研究，并确定了B细胞和T细胞表位。肺出血肾炎自身抗体表位是“隐蔽的”，因为它们在结构上被IV型胶原α4和α5的相邻非胶原结构域所隔离。对大鼠的T细胞表位研究表明，一个13聚体可诱导实验性自身免疫性肾小球肾炎。肺出血肾炎综合征患者的T细胞识别两个表位，位于内体蛋白酶对抗原加工高度敏感的区域。肺出血肾炎综合征与HLA DRB1基因密切相关，其中DRB11501赋予易感性，而DRB10701和DRB1*0101具有主要保护作用。实验数据表明自身抗体和细胞介导的免疫均为疾病效应因子。对人类的观察表明，调节性T细胞与疾病恢复期自身免疫调节的发展有关。
