Jaume J C, Portolano S, Prummel M F, McLachlan S M, Rapoport B
Thyroid Molecular Biology Unit, Veterans Administration Medical Center, San Francisco, California 94121.
J Clin Endocrinol Metab. 1994 Feb;78(2):348-52. doi: 10.1210/jcem.78.2.8106623.
Graves' ophthalmopathy is a distressing autoimmune disease of unknown etiology. Analysis of the genes for antibodies secreted by orbital tissue-infiltrating plasma cells might provide insight into the pathogenesis of this disease. We, therefore, constructed an immunoglobulin heavy (H) chain and an immunoglobulin kappa light (L) chain cDNA library from the orbital tissue of a patient with active Graves' ophthalmopathy. Analysis of 15 H (IgG1) and 15 L (kappa) chains revealed a restricted spectrum of variable region genes. Fourteen of 15 variable kappa genes were about 94% homologous to the closest known germline gene, KL012. Thirteen of 15 H chain genes were 91% and 90% homologous to the closest germline genes, DP10 and hv1263, respectively. Remarkably, these germline genes also code for other autoantibodies to striated muscle (KL012) and thyroid peroxidase (KL012 and hv1263). These studies raise the possibility that particular germline genes may be associated with autoimmunity in humans. Further, the present study opens the way to identifying ocular autoantigens that may be the target of an humoral immune response.
格雷夫斯眼病是一种病因不明的令人痛苦的自身免疫性疾病。分析眼眶组织浸润浆细胞分泌的抗体基因可能有助于深入了解这种疾病的发病机制。因此，我们从一名患有活动性格雷夫斯眼病患者的眼眶组织构建了免疫球蛋白重链（H）和免疫球蛋白κ轻链（L）cDNA文库。对15条H（IgG1）链和15条L（κ）链的分析揭示了可变区基因的有限谱。15条可变κ基因中的14条与最接近的已知种系基因KL012的同源性约为94%。15条H链基因中的13条分别与最接近的种系基因DP10和hv1263的同源性为91%和90%。值得注意的是，这些种系基因还编码针对横纹肌（KL012）和甲状腺过氧化物酶（KL012和hv1263）的其他自身抗体。这些研究提出了特定种系基因可能与人类自身免疫相关的可能性。此外，本研究为鉴定可能是体液免疫反应靶点的眼部自身抗原开辟了道路。
