CN113512582A - Slc22a18在过敏***反应性疾病与炎症性疾病中的应用 - Google Patents

Slc22a18在过敏***反应性疾病与炎症性疾病中的应用 Download PDF

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CN113512582A
CN113512582A CN202110403721.7A CN202110403721A CN113512582A CN 113512582 A CN113512582 A CN 113512582A CN 202110403721 A CN202110403721 A CN 202110403721A CN 113512582 A CN113512582 A CN 113512582A
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张宗豪
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Abstract

本发明涉及SLC22A18在过敏***反应性疾病与炎症性疾病中的应用。本发明发现SLC22A18基因与过敏***反应性疾病与炎症性疾病关系密切，可作为相关的生物标志物，为小儿过敏找到新的潜在的临床诊治靶点。

Description

SLC22A18在过敏***反应性疾病与炎症性疾病中的应用
技术领域
本发明属于基因领域，特别涉及一种SLC22A18在过敏***反应性疾病与炎症性疾病中的应用。
背景技术
过敏***反应性疾病是指人体与抗原物质接触后发生的不正常的免疫反应，导致生理功能的紊乱或组织的损伤。临床称之为***反应性疾病(过敏性疾病)。过敏性疾病已成为新世纪的流行病，因药物、食物等过敏原诱发。随着我国社会经济发展及环境变化，小儿过敏性疾病发病率在我国有明显增加的趋势，如何进行正确诊断及处理成为临床重要问题。
发明内容
本发明所要解决的技术问题是提供一种SLC22A18在过敏***反应性疾病与炎症性疾病中的应用，该应用为小儿过敏找到新的潜在的临床诊治靶点。
本发明提供了一种SLC22A18在过敏***反应性疾病与炎症性疾病中的应用，其特征在于：用于制备诊断试剂、检测试剂或试剂盒。
所述诊断试剂包括抗体、引物、探针、测序文库、核酸芯片或蛋白质芯片。
所述检测试剂包括SLC22A18的特异性抗体、SLC22A18的特异性结合分子、特异性扩增引物、探针或芯片。
所述试剂盒含有一容器，所述容器中含有检测SLC22A18基因、mRNA、cDNA或蛋白的检测试剂；以及标签或说明书。
本发明还提供了一种SLC22A18在过敏***反应性疾病与炎症性疾病中的应用，用于制备过敏***反应性疾病与炎症性疾病的药物。
所述药物以SLC22A18为靶向，配以药学上可接受的辅料或辅助性成分制备成制剂使用。
所述制剂包括片剂、粉剂、颗粒剂、胶囊、口服液或缓释剂。
有益效果
本发明发现SLC22A18基因与过敏***反应性疾病与炎症性疾病关系密切，可作为相关的生物标志物，为小儿过敏找到新的潜在的临床诊治标志物及靶点。
附图说明
图1为6例SLC22A18相关综合征临床特征时间线；
图2A-B为流式细胞仪检测SLC22A18细胞亚群表达水平；
图3为SLC22A18的核心基因调控关系。
具体实施方式
下面结合具体实施例，进一步阐述本发明。应理解，这些实施例仅用于说明本发明而不用于限制本发明的范围。此外应理解，在阅读了本发明讲授的内容之后，本领域技术人员可以对本发明作各种改动或修改，这些等价形式同样落于本申请所附权利要求书所限定的范围。
实施例1
自2013年11月至2020年8月，来自6个不同家庭的6名患者因生长迟缓就诊。患儿出生时体重和身高正常，但随着时间的增长，他们逐渐出现生长障碍，体重增长缓慢和生长速度低等瘦小的表现。追问病史，有趣的发现，他们在幼儿期成长过程中有过敏等多种表现，如哮喘、腺样体肥大、夜间打鼾和睡眠障碍等，而且反反复复、难以治愈。而到了***发育时期，他们又体重快速增加，四肢并无肥壮的表现(图1)。再通过家族史调查发现，患儿们的父亲或祖父在他们的儿童时期也有类似的生长迟缓和过敏症状；在青少年发育早期也是迅速变胖，在成年早期出现脂肪肝。因此，我们又采用B超检查了这6名患儿的肝脏，同样吃惊地发现超声图像显示其中2人已患有脂肪肝。在这些患者中，没有出现性发育迟缓和智力发育迟缓；在血常规检查中发现了淋巴细胞增多、中性粒细胞减少、单核细胞增多和嗜酸性或碱性细胞增殖的趋势；在血生化检查中发现了VitD3、IGF-1、IGF-3BP水平均下降；脑下垂体MRI检查中未见异常。
有趣的是这些病例都是男性患儿，他们血中的FFAs总是高于正常对照组。而且，6例患儿的祖父母和父亲均在他们儿时生长发育过程中表现出与本研究报道患儿相同的症状群，既反复的过敏症状、身材的矮小和内脏脂肪肝的发生。患儿的祖父母和父亲都没有接受rhGH治疗，终身高不足170cm，脂肪肝、内脏脂肪堆积，向心性肥胖的体态(表1)。
表1 6例SLC22A18的临床特征和实验室结果总结
Figure BDA0003021390490000021
Figure BDA0003021390490000031
Figure BDA0003021390490000041
Figure BDA0003021390490000051
抑制SLC22A18可通过减少自噬作用促进肝脏内脂质积累。这些发现可以解释病例中脂肪肝的发展。此外，还发现SLC22A18在患者外周血中的表达水平较低。巨噬细胞在先天免疫和获得性免疫中发挥显著作用，与哮喘和食物过敏密切相关。进一步通过流式细胞术发现SLC22A18在外周血巨噬细胞中以低表达为主，提示SLC22A18与过敏性免疫疾病有关患者(图2A-B)。最后，图3表明，经过查新https:www.string-db.org/***，目前还未发现SLC22A18有与过敏反应相关的通路报道。本发明首次报道SLC22A18基因与过敏***反应性疾病与炎症性疾病关系密切，可作为相关的生物标志物，为小儿过敏性疾病找到新的潜在的临床治疗靶点。

Claims (7)

1.一种SLC22A18在过敏***反应性疾病与炎症性疾病中的应用，其特征在于：用于制备诊断试剂、检测试剂或试剂盒。
2.根据权利要求1所述的应用，其特征在于：所述诊断试剂包括抗体、引物、探针、测序文库、核酸芯片或蛋白质芯片。
3.根据权利要求1所述的应用，其特征在于：所述检测试剂包括SLC22A18的特异性抗体、SLC22A18的特异性结合分子、特异性扩增引物、探针或芯片。
4.根据权利要求1所述的应用，其特征在于：所述试剂盒含有一容器，所述容器中含有检测SLC22A18基因、mRNA、cDNA或蛋白的检测试剂；以及标签或说明书。
5.一种SLC22A18在过敏***反应性疾病与炎症性疾病中的应用，其特征在于：用于制备过敏***反应性疾病与炎症性疾病的药物。
6.根据权利要求5所述的应用，其特征在于：所述药物以SLC22A18为靶向，配以药学上可接受的辅料或辅助性成分制备成制剂使用。
7.根据权利要求6所述的应用，其特征在于：所述制剂包括片剂、粉剂、颗粒剂、胶囊、口服液或缓释剂。
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