Towers Rebecca J, Bolm Maike, Currie Bart J, Chhatwal Gursharan S, Fagan Peter K
Tropical and Emerging Infectious Diseases Division, Menzies School of Health Research, Darwin, Australia.
Ann N Y Acad Sci. 2009 Sep;1173:83-91. doi: 10.1111/j.1749-6632.2009.04653.x.
Acute rheumatic fever (ARF) is an autoimmune sequela of group A streptococcal infection mostly affecting school-aged children. Recurrent episodes of ARF can result in the development of rheumatic heart disease (RHD). One in 40 indigenous Australians in the Northern Territory is affected by RHD. This disease mostly impacts young people; 45% of those who require heart valve surgery in Australia due to RHD are younger than 25 years old. ARF is characterized by autoimmune attack of the heart; therefore, the presence of the autoantibodies involved could potentially be used to diagnose ARF. To this end, a human heart cDNA library was screened with serum from a patient with ARF, and 12 autoreactive human heart antigens were identified. They include five different IgG heavy chains and a range of tissue-specific cell-signaling proteins, species of which have been implicated in other autoimmune diseases. Preliminary ELISA results show that ARF patients have significantly higher levels of antibodies recognizing the cardiac autoantigens than controls. These antigens are promising candidates for the development of a serological assay for the diagnosis of ARF. The nature of the proteins identified has exciting implications for future research into the pathogenesis of ARF.
急性风湿热(ARF)是A组链球菌感染后的一种自身免疫性后遗症,主要影响学龄儿童。ARF的反复发作可导致风湿性心脏病(RHD)的发生。北领地每40名澳大利亚原住民中就有1人受RHD影响。这种疾病主要影响年轻人;在澳大利亚因RHD需要进行心脏瓣膜手术的患者中,45%年龄小于25岁。ARF的特征是心脏受到自身免疫攻击;因此,相关自身抗体的存在有可能用于诊断ARF。为此,用一名ARF患者的血清筛选了一个人类心脏cDNA文库,鉴定出12种自身反应性人类心脏抗原。它们包括5种不同的IgG重链和一系列组织特异性细胞信号蛋白,其中一些蛋白已在其他自身免疫性疾病中被涉及。初步酶联免疫吸附测定(ELISA)结果显示,ARF患者识别心脏自身抗原的抗体水平显著高于对照组。这些抗原有望用于开发诊断ARF的血清学检测方法。所鉴定蛋白质的性质对ARF发病机制的未来研究具有令人兴奋的意义。