Membrane-Bound Complement Regulatory Proteins as Biomarkers and Potential Therapeutic Targets for SLE
Membrane-Bound Complement Regulatory Proteins as Biomarkers and Potential Therapeutic Targets for SLE
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DOI：
10.1007/978-1-4614-4118-2_4
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发表时间：
2013-01-01
期刊：
影响因子：
--
通讯作者：
Khera, Rohan
中科院分区：
文献类型：
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作者：
Das, Nibhriti;Biswas, Bintili;Khera, Rohan
在过去的二十年里，人们对补体调节蛋白在自身免疫性疾病中的作用以及补体抑制剂作为治疗药物的重要性的理解取得了显着的进展。系统性红斑狼疮是系统性自身免疫性疾病的原型。这种疾病虽然罕见，但可能致命，并影响育龄妇女。这是一种涉及多器官的复杂疾病，每个患者都会出现不同的症状。诊断通常很困难，并且基于美国风湿病协会制定的诊断标准。抗核抗体，更具体地说，抗双链 DNA 的存在表明存在 SLE。由于该疾病是多因素影响的且其表型具有高度异质性，因此需要确定 SLE 的多种非侵入性生物标志物。缺乏针对 SLE 疾病活动性或治疗反应的经过验证的生物标志物是疾病有效管理、药物发现以及新疗法开发的障碍。最近对基因敲除小鼠的研究表明，膜结合补体调节蛋白（CRP）可能关键地决定宿主组织对自身免疫和炎症性疾病中补体损伤的敏感性。我们实验室进行的病例对照和随访研究表明，DAF、MCP、CR1 和 CD59 转录物水平与 SLE 疾病活动度之间存在密切关系。基于对这四种膜结合补体调节蛋白数据的比较评估，我们设想 CR1 和 MCP 转录本作为假定的非侵袭性疾病活动标记，并将各自的蛋白质作为 SLE 的治疗靶点。以下是对膜结合补体调节蛋白 DAF、MCP、CR1 和 CD59 作为 SLE 生物标志物和治疗靶点的简要评价。
For the last two decades, there had been remarkable advancement in understanding the role of complement regulatory proteins in autoimmune disorders and importance of complement inhibitors as therapeutics. Systemic lupus erythematosus is a prototype of systemic autoimmune disorders. The disease, though rare, is potentially fatal and afflicts women at their reproductive age. It is a complex disease with multiorgan involvement, and each patient presents with a different set of symptoms. The diagnosis is often difficult and is based on the diagnostic criteria set by the American Rheumatology Association. Presence of antinuclear antibodies and more specifically antidouble-stranded DNA indicates SLE. Since the disease is multifactorial and its phenotypes are highly heterogeneous, there is a need to identify multiple noninvasive biomarkers for SLE. Lack of validated biomarkers for SLE disease activity or response to treatment is a barrier to the efficient management of the disease, drug discovery, as well as development of new therapeutics. Recent studies with gene knockout mice have suggested that membrane-bound complement regulatory proteins (CRPs) may critically determine the sensitivity of host tissues to complement injury in autoimmune and inflammatory disorders. Case-controlled and follow-up studies carried out in our laboratory suggest an intimate relation between the level of DAF, MCP, CR1, and CD59 transcripts and the disease activity in SLE. Based on comparative evaluation of our data on these four membrane-bound complement regulatory proteins, we envisaged CR1 and MCP transcripts as putative noninvasive disease activity markers and the respective proteins as therapeutic targets for SLE. Following is a brief appraisal on membrane-bound complement regulatory proteins DAF, MCP, CR1, and CD59 as biomarkers and therapeutic targets for SLE.