Esch T R, Poveromo J D, Aikins M C, Levanos V A
Department of Immunology, Forsyth Institute, Boston, MA 02115, USA.
Scand J Immunol. 2002 Mar;55(3):304-10. doi: 10.1046/j.1365-3083.2002.01042.x.
Recent research has demonstrated a crucial role for autoantibodies in the pathogenesis of Sjögren's syndrome (SS)-like disease in the non-obese diabetic (NOD) mouse, but it remains to be determined which antibody species among all those present are directly related to the various aspects of pathology. To identify autoantigens in the NOD mouse system, we have taken the approach of using immunoglobulin (Ig)G purified from sera of NOD mice exhibiting SS-like symptoms to screen cDNA expression libraries derived from exocrine gland mRNA. Here we report the identification of a novel autoantigen, designated LGP10, expressed in lacrimal and submandibular glands. Autoantibodies to this protein are prominent in the sera of NOD mice starting at 11-12 weeks of age, but not in control nonautoimmune mice. LGP10 has no known function, but bears similarities to various other proteins produced by epithelia. Interestingly, all of these similar proteins have been linked to immunosuppression and/or steroid binding, both processes that could have a significant impact on pathological features of SS.
最近的研究表明,自身抗体在非肥胖型糖尿病(NOD)小鼠的干燥综合征(SS)样疾病发病机制中起关键作用,但目前仍有待确定所有存在的抗体种类中,哪些与病理学的各个方面直接相关。为了在NOD小鼠系统中鉴定自身抗原,我们采用了从表现出SS样症状的NOD小鼠血清中纯化免疫球蛋白(Ig)G的方法,来筛选源自外分泌腺mRNA的cDNA表达文库。在此,我们报告鉴定出一种新的自身抗原,命名为LGP10,它在泪腺和颌下腺中表达。针对这种蛋白质的自身抗体在11至12周龄的NOD小鼠血清中很突出,但在对照非自身免疫小鼠中则没有。LGP10没有已知功能,但与上皮细胞产生的各种其他蛋白质有相似之处。有趣的是,所有这些相似的蛋白质都与免疫抑制和/或类固醇结合有关,这两个过程都可能对SS的病理特征产生重大影响。