CN113834940A - 间质性膀胱炎/膀胱疼痛综合征诊断试剂盒 - Google Patents
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Abstract
本发明涉及生物医学技术领域,公开了间质性膀胱炎/膀胱疼痛综合征诊断试剂盒,所述试剂盒用于联合检测患者尿液中的IgE和CCL5,当患者尿液中IgE和CCL5的量分别达到IgE>0.41mg/ml、CCL5>75.32ng/ml时可确定患者患有间质性膀胱炎/膀胱疼痛综合征。本发明可通过联合检测尿液中的IgE和炎症因子CCL5来诊断患者是否患有IC/BPS,本发明避免了现有技术诊断的侵入性和伤害性,为IC/BPS诊断的准确性、实效性和可操作性开辟了新的方向。
Description
技术领域
本发明涉及生物医学技术领域,具体涉及间质性膀胱炎/膀胱疼痛综合征诊断试剂盒。
背景技术
间质性膀胱炎/膀胱疼痛综合征(IC/BPS)是目前妇科泌尿领域最为棘手的一种疾病,其主要的临床表现为尿频和膀胱剧烈疼痛。临床常用的治疗方案在长期的随访中效果均不佳,约10%的患者最终会因为无法忍受该疾病带来的痛苦和精神压力,选择膀胱全切。该疾病的存在已有超过100年历史,但至今病因不明,给诊断和治疗带来了极大的挑战。
目前的诊断主要依靠排他诊断,在排除泌尿外科容易引起下尿路症状的其他疾病(肿瘤、结石、感染)之后,通过经尿道膀胱镜获取膀胱组织进行活检才能得到最终诊断,该过程常需2-11年,困难的诊断过程常常会延长甚至延误患者的治疗时间。目前,不论是在学术界还是临床实践中,均没有一种公认的快速诊断方式。因此,发明人基于IC/BPS与健康对照者的膀胱组织测序结果,发现了IC/BPS与健康对照者中的差异表达因子,可针对该因子研发用于诊断IC/BPS的试剂盒。
发明内容
基于以上问题,本发明提供间质性膀胱炎/膀胱疼痛综合征诊断试剂盒,该试剂盒通过联合检测尿液中的IgE和CCL5来诊断患者是否患有IC/BPS。
为解决以上技术问题,本发明提供了间质性膀胱炎/膀胱疼痛综合征诊断试剂盒,所述试剂盒用于联合检测患者尿液中的IgE和CCL5,当患者尿液中IgE和CCL5的量分别达到IgE>0.41mg/ml、CCL5>75.32ng/ml时可确定患者患有间质性膀胱炎/膀胱疼痛综合征。
与现有技术相比,本发明的有益效果是:本发明可通过联合检测尿液中的IgE和炎症因子CCL5来诊断患者是否患有IC/BPS,本发明避免了现有技术诊断的侵入性和伤害性,为IC/BPS诊断的准确性、实效性和可操作性开辟了新的方向。
附图说明
图1为本发明的实施例的测序结果中细胞类型以及在病例和对照中所占比例的结果图;
图2为本发明的实施例的单细胞测序和质谱流式细胞学分析所敲定的细胞类型之间的相关性结果图;
图3为本发明的实施例的IC/BPS患者和健康对照者的尿液中IgE的浓度对比图和用ELISA方法检测的间质性膀胱炎/膀胱疼痛综合征患者和对照者尿液中CCL5的浓度对比图;
图4为本发明的实施例中CCL5被发现的过程图。
具体实施方式
为使本发明的目的、技术方案和优点更加清楚明白,下面结合实施例和附图,对本发明作进一步的详细说明,本发明的示意性实施方式及其说明仅用于解释本发明,并不作为对本发明的限定。
实施例:
本实施例从21名参与者(15名IC/BPS患者和6名对照者)的膀胱组织中分选免疫细胞,通过单细胞测序建立了IC/BPS膀胱免疫细胞图谱,测序结果中细胞类型以及在病例和对照中所占比例见附图1,图1展示了某一细胞类型在病例组和对照组中的比例,红色(灰化之后的图1中阴影更深的部分)代表间质性膀胱炎/膀胱疼痛综合征组,蓝色(灰化之后的图1中阴影较浅的部分)代表健康对照组;横坐标代表细胞类型,纵坐标代表细胞所占比例。前四列均为B细胞(包括浆细胞、静息B细胞、记忆B细胞以及IGHG低表达B细胞),可见大部分B细胞来源于间质性膀胱炎/膀胱疼痛综合征患者,几乎所有浆细胞均来源于间质性膀胱炎/膀胱疼痛综合征患者。重要的是,浆细胞正是产生抗体的专职细胞,抗体包括IgA、IgE、IgG、IgM、IgD。
本实施例通过单细胞测序发现了22种细胞类型,在进一步探究细胞功能之前,发明人采用质谱流式细胞学(5名IC/BPS患者和5名对照)研究验证了单细胞中的细胞分群。见附图2,图中的方格颜色越深代表相关性越高,横坐标为质谱流式中发现的细胞分群,纵坐标为单细胞测序中发现的细胞分群,黑色框(灰化之后的图2中左上角的框)代表两种分析中T细胞类型的相关性,紫色框(灰化之后的图2中中间的框)代表B细胞类型的相关性,绿色框(灰化之后的图2中右下角的框)代表髓系细胞类型的相关性。可见三种细胞类型均有大于0.5的相关性,即,质谱流式细胞学发现的细胞群与单细胞测序发现的细胞群高度相关,细胞类型确实存在,B细胞存在。
本实施例在确认B细胞存在之后,进一步探究了B细胞的功能。从B细胞的分布中可见浆细胞几乎来源于间质性膀胱炎/膀胱疼痛综合征患者,而浆细胞的功能主要是分泌抗体。因此发明人取20例患者和14例健康对照者的尿液标本,对尿液中的抗体进行了检测。见附图3,图中IC/BPS患者组的数值点代表间质性膀胱炎/膀胱疼痛综合征患者尿液中IgE抗体的测量值,健康对照者的数值点代表对照组尿液中IgE抗体的测量值,P<0.05认为差异具有统计学意义。从图3中可见间质性膀胱炎/膀胱疼痛综合征患者尿液中IgE抗体的浓度显著高于对照组,实验中检测到的其他抗体无统计学差异。
此外,发明人通过研究还发现IC/BPS患者膀胱组织中表达量最高的炎症因子为CCL5,其与对照组相比具有统计学差异,高水平的CCL5同样在IC/BPS患者的尿液中被验证。见附图4,其中黑色点代表CCL5在各个细胞类型中的表达量,横坐标代表细胞类型,纵坐标代表表达量。从图4可见CCL5在几乎所有细胞类型中均高表达。见附图3,可见间质性膀胱炎/膀胱疼痛综合征患者尿液中CCL5表达更高,P<0.05,差异具有统计学意义。
综上所述,本实施例为了减少IC/BPS诊断的侵入性和伤害性,增加IC/BPS诊断的准确性、实效性和可操作性,可通过检测尿液中IgE和CCL5的含量来联合诊断IC/BPS。
表1尿液中IgE检测数据
表2尿液中CCL5检测数据
见表1和表2,在间质性膀胱炎/膀胱疼痛综合征患者和健康对照者尿液中IgE均值(最小值,最大值)分别为0.41(0.33,0.64)mg/ml和0.33(0.29,0.37)mg/ml,CCL5的分别为75.32(66.58,84.87)ng/ml和67.47(59,75.01)ng/ml。对照者尿液中,IgE和CCL5的最大值均低于间质性膀胱炎/膀胱疼痛综合征患者尿液中IgE和CCL5的均值,因此,当被检测患者尿液中IgE和CCL5的量分别达到IgE>0.41mg/ml、CCL5>75.32ng/ml时可确定患者患有间质性膀胱炎/膀胱疼痛综合征。
如上即为本发明的实施例。上述实施例以及实施例中的具体参数仅是为了清楚表述发明验证过程,并非用以限制本发明的专利保护范围,本发明的专利保护范围仍然以其权利要求书为准,凡是运用本发明的说明书及附图内容所作的等同结构变化,同理均应包含在本发明的保护范围内。
Claims (1)
1.间质性膀胱炎/膀胱疼痛综合征诊断试剂盒,其特征在于,所述试剂盒用于联合检测患者尿液中的IgE和CCL5,当患者尿液中IgE和CCL5的量分别达到IgE>0.41mg/ml、CCL5>75.32ng/ml时可确定患者患有间质性膀胱炎/膀胱疼痛综合征。
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Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
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AU2004274909A1 (en) * | 2003-09-15 | 2005-03-31 | Oklahoma Medical Research Foundation | Method of using cytokine assays to diagnose, treat, and evaluate inflammatory and autoimmune diseases |
US20070015167A1 (en) * | 2005-07-15 | 2007-01-18 | Tss Biotech Inc. | Method for detecting vesicoureteral reflux or interstitial cystitis |
WO2011031757A1 (en) * | 2009-09-11 | 2011-03-17 | Centocor Ortho Biotech Inc. | Serum markers for identification of cutaneous systemic sclerosis subjects |
US20120263733A1 (en) * | 2002-11-15 | 2012-10-18 | Morehouse School Of Medicine | Anti-cxcl9, anti-cxcl10, anti-cxcl11, anti-cxcl13, anti-cxcr3 and anti-cxcr5 agents for inhibition of inflammation |
US20200164030A1 (en) * | 2017-06-14 | 2020-05-28 | Biomedical Research Institute | Use of Interleukin-4-Inducing Principle of Schistosoma mansoni Eggs for Treating Pain, Interstitial Cystitis and/or Overactive Bladder |
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US20120263733A1 (en) * | 2002-11-15 | 2012-10-18 | Morehouse School Of Medicine | Anti-cxcl9, anti-cxcl10, anti-cxcl11, anti-cxcl13, anti-cxcr3 and anti-cxcr5 agents for inhibition of inflammation |
AU2004274909A1 (en) * | 2003-09-15 | 2005-03-31 | Oklahoma Medical Research Foundation | Method of using cytokine assays to diagnose, treat, and evaluate inflammatory and autoimmune diseases |
US20070015167A1 (en) * | 2005-07-15 | 2007-01-18 | Tss Biotech Inc. | Method for detecting vesicoureteral reflux or interstitial cystitis |
WO2011031757A1 (en) * | 2009-09-11 | 2011-03-17 | Centocor Ortho Biotech Inc. | Serum markers for identification of cutaneous systemic sclerosis subjects |
US20200164030A1 (en) * | 2017-06-14 | 2020-05-28 | Biomedical Research Institute | Use of Interleukin-4-Inducing Principle of Schistosoma mansoni Eggs for Treating Pain, Interstitial Cystitis and/or Overactive Bladder |
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