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狼疮肾炎患者肾小球外补体c1q沉积的临床病理意义

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中华肾脏病杂志 2024年第4期40卷 270-276页

作者：杨晓青黄岩杰杨月丽毕亮亮张秋爽丁樱任献青翟文生河南中医药大学儿科医学院郑州450046 河南中医药大学第一附属医院肾脏病理实验室郑州450000

目的了解狼疮肾炎(lupus nephritis,LN)患者肾小球外补体c1q的沉积情况,探讨其临床病理意义,为LN肾小管间质损伤机制提供免疫学证据。方法该研究为横断面研究。收集2019年3月1日至2023年6月30日河南中医药大学第一附属医院经肾活检证实... 详细信息

目的了解狼疮肾炎(lupus nephritis,LN)患者肾小球外补体c1q的沉积情况,探讨其临床病理意义,为LN肾小管间质损伤机制提供免疫学证据。方法该研究为横断面研究。收集2019年3月1日至2023年6月30日河南中医药大学第一附属医院经肾活检证实的LN患者的临床资料。石蜡切片直接免疫荧光法检测肾小球外即肾小管基底膜、肾小管周毛细血管和肾间质小动脉c1q的沉积,连续切片分析c1q表达与相应组织病变的关系。Pearson相关分析法或Spearman秩相关分析法分析c1q表达水平与肾组织病理评分(活动性肾小管间质指数、活动性肾小球指数、活动性指数、慢性肾小管间质指数、慢性肾小球指数、慢性指数)、肾损伤临床指标(24 h尿蛋白量、尿α1微球蛋白、尿N-乙酰β-D-葡萄糖苷酶、血肌酐)的相关性。结果该研究纳入LN患者71例,年龄(20.83±11.77)岁(7~48岁),其中男性14例(19.72%),女性57例(80.28%)。LN病例分型Ⅱ型6例,Ⅲ型21例,Ⅳ型18例,Ⅴ型8例,Ⅲ+Ⅴ型12例,Ⅳ+Ⅴ型6例。石蜡切片分析结果显示,肾小管基底膜和/或肾小管周毛细血管和/或肾间质小动脉c1q阳性60例(84.51%),以肾小管基底膜阳性率最高(50例,70.42%)。c1q在肾小管基底膜呈散在或局灶沉积44例(61.97%)。c1q在肾小管周毛细血管呈散在或局灶沉积32例(45.07%)。肾小管基底膜c1q阳性比例以LNⅣ型(15/18)最高。肾小管周毛细血管c1q阳性比例以LNⅡ型(5/6)最高。肾组织连续切片结果显示,c1q主要表达在肾小管间质炎症病变区域,肾小管萎缩区域无c1q阳性表达。相关性分析结果显示,肾小管基底膜c1q阳性百分比与活动性肾小管间质指数(r=0.640,P1)、尿α1微球蛋白(r=0.573,P1)、尿N-乙酰-β-D-葡萄糖苷酶(r=0.404,P=0.008)及血肌酐(r=0.399,P=0.001)均呈正相关,与其他肾组织病理评分和24 h尿蛋白量均无相关性。c1q肾小管周毛细血管与24 h尿蛋白量、尿α1微球蛋白、尿N-乙酰β-D-葡萄糖苷酶、血肌酐和肾组织病理评分均无相关性。结论c1q在肾小管基底膜沉积可能是肾小管间质损伤的原因之一,建议在常规肾脏病理诊断中予以标注。

关键词：狼疮肾炎 c1q 肾小管基底膜肾小管周毛细血管

Association of serum complement c1q with cardiovascular outcomes among patients with acute coronary syndrome undergoing percutaneous coronary intervention

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Journal of Geriatric cardiology 2022年第12期19卷 949-959,1007-1010页

作者： qiu-Xuan LI Xiao-Teng MA qiao-Yu SHAO Zhi-qiang YANG Jing LIANG Li-Xia YANG Dong-Mei SHI Yu-Jie ZHOU Zhi-Jian WANG Department of cardiology Beijing Anzhen HospitalCapital Medical UniversityBeijing Institute of Heart Lung and Blood Vessel DiseaseBeijing Key Laboratory of Precision Medicine of Coronary Atherosclerotic DiseaseClinical Center for Coronary Heart DiseaseCapital Medical UniversityBeijingChina

OBJEcTIVE To determine the association of serum complement c1q levels with cardiovascular outcomes among patients with acute coronary syndrome(AcS)undergoing percutaneous coronary intervention(PcI),and evaluate the value of c1q modified by high-sensitivity c-reactive protein(hs-cRP)levels as an independent *** As a single-center prospective observational study,we analyzed 1701 patients who had received primary or elective PcI for AcS at Beijing Anzhen Hospital,capital Medical University,Beijing,china between June 1,2016 and November 30,*** associations of c1q modified by hs-cRP with major adverse cardiovascular events(MAcE)were determined in survival *** Patients with the lowest c1q tertile had the highest cumulative risk of MAcE(log-rank P=0.007).In fully adjusted cox regression models,stratifying the total population according to hs-cRP dichotomy,c1q was significantly associated with MAcE in patients with hs-cRP levels less than 2 mg/L but not in those with 2 mg/L or more(P_(interaction)=0.02).In patients with hs-cRP levels less than 2 mg/L,with the lowest c1q tertile as reference,the risk of MAcE was reduced by 40.0%in the middle c1q tertile[hazard ratio(HR)=0.600,95%cI:0.423–0.852,P=0.004]and by 43.9%in the highest c1q tertile(HR=0.561,95%cI:0.375–0.840,P=0.005).cONcLUSIONS Serum complement c1q is significantly associated with cardiovascular outcomes in patients with AcS undergoing PcI,only when hs-cRP levels are less than 2 mg/*** finding implicates the usefulness of c1q for the risk stratification in AcS patients with reduced systemic inflammation.

关键词： c1q patients coronary

c1q recognizes antigen-bound IgG in a curvature-dependent manner

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Nano Research 2020年第6期13卷 1651-1658页

作者： christina M.Zeuthen Ali Shahrokhtash Karin Fromell Kristina Nilsson Ekdahl Hossein Mohammad-Beigi Duncan S.Sutherland Interdisciplinary Nanoscience center Aarhus UniversityGustav Wieds vej 148000Aarhus CDenmark Department of Immunology Genetics and PathologyUppsala UniversityDag Hammarskjölds väg 2075185UppsalaSweden Linnaeus center of Biomaterials chemistry Linnaeus University39182KalmarSweden Sino-Danish center for Education and Research Niels Jensens Vej 2Building 11908000Aarhus CDenmark The centre for cellular Signal Patterns(cellPAT) Gustav Wieds vej 148000Aarhus CDenmark

Nano Research volume 13,pages1651–1658(2020)cite this article 109 Accesses Metrics details Abstract c1q is an important recognition protein in the complement system,which is a major protein cascade in the innate immune *** recognition of a target by c1q,the target is marked for opsonization and destruction.c1q recognizes many pathogenic patterns directly,but an important target is the Fc domain of antibodies binding to their *** this paper,the curvature-dependence of the interaction between IgG and c1q is studied by surface plasmon resonance and quartz crystal *** is organized in similar surface coverage densities on flat polystyrene surfaces and polystyrene nanoparticles of different sizes,and the amount of c1q binding to the IgG is *** in solution were found to aggregate upon incubation with IgG,and therefore a new technique utilizing nanoparticles binding to antifouling polymer brush functionalized surfaces was used to prepare surfaces with nanoparticles for measurements with surface plasmon *** antigen-bound IgG at the curved surface of nanoparticles showed 5.6 times lower binding of c1q compared to at matched flat *** was no significant difference between the binding at 100 and 200 nm polystyrene *** findings are important for designing drug delivery systems to evade the complement system.

关键词： c1q complement system antibodies curvature nanoparticles

Interactions of complement proteins c1q and factor H with lipid A and Escherichia coli:further evidence that factor H regulates the classical complement pathway

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Protein & cell 2011年第4期2卷 320-332页

作者： Lee Aun Tan Andrew c.Yang Uday Kishore Robert B.Sim Medical Research council Immunochemistry Unit Department of BiochemistryUniversity of OxfordSouth Parks RoadOxford OX13QUUK Present address:Department of Immunology Faculty of MedicineImperial College LondonHammersmith HospitalDu Cane RoadLondon W120NNUK St Peter’s college New Inn Hall St.Oxford OX12DLUK Present address:SUNY Downstate college of Medicine 450 Clarkson Avenue BrooklynNY 11203USA Weatherall Institute of Molecular Medicine John Radcliffe HospitalUniversity of OxfordHeadingtonOxford OX39DSUK Present address:center for Infection Immunity and Disease MechanismsBiosciencesSchool of Health Sciences and Social CareBrunel UniversityUxbridge UB83PH West LondonUK Present address:Department of Pharmacology University of OxfordMansfield RoadOxford OX13QTUK

Proteins of the complement system are known to interact with many charged *** recently characterized binding of c1q and factor H to immobilized and liposomal anionic *** H inhibited c1q binding to anionic phospholipids,suggesting a role for factor H in regulating activation of the complement classical pathway by anionic *** extend this finding,we examined interactions of c1q and factor H with lipid A,a well-characterized activator of the classical *** report that c1q and factor H both bind to immobilized lipid A,lipid A liposomes and intact Escherichia coli *** H competes with c1q for binding to these ***,increasing the factor H:c1q molar ratio in serum diminished c4b fixation,indicating that factor H diminishes classical pathway *** recombinant forms of the cterminal,globular heads of c1q A,B and c chains bound to lipid A and *** in a manner qualitatively similar to native c1q,confirming that c1q interacts with these targets via its globular head *** observations reinforce our proposal that factor H has an additional complement regulatory role of down-regulating classical pathway activation in response to certain *** is distinct from its role as an alternative pathway *** suggest that under physiological conditions,factor H may serve as a downregulator of bacterially-driven inflammatory responses,thereby finetuning and balancing the inflammatory response in infections with Gram-negative bacteria.

关键词： complement lipid A bacteria factor H c1q

The classical and Regulatory Functions of c1q in Immunity and Autoimmunity

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cellular & Molecular Immunology 2008年第1期5卷 9-21页

作者： Jinhua Lu Boon King Teh Linda Wang Yinan Wang Yen Seah Tan Min chern Lai Kenneth B. M. Reid Department of Microbiology Yong Loo Lin School of Medicine and 2NUS Immunology Program National University of Singapore Blk MD4 5 Science Drive 2 Singapore 117597 MRc Immunochemistry Unit Department of Biochemistry University of Oxford South Parks Road Oxford OXI 3QU UK

A classical function of clq is to bind immune complexes and initiate complement activation producing membrane lytic complexes, opsonins and anaphylatoxins. This classical pathway of complement activation is also elicited when clq binds some other ligands. Besides complement activation, clq also regulates cell differentiation, adhesion, migration, activation and survival. clq deficiency is associated with autoimmunity as well as increased susceptibility to infections. In this article, we discuss the basic properties of clq, its expression, and classical and regulatory functions. cellular ＆ Molecular Immunology.

关键词： c1q macrophage dendritic cell apoptotic cell autoimmunity

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血清补体c1q测定在恶性肿瘤诊断中的意义

陆军军医大学学报 2023年第23期45卷 2485-2489页

作者：王云龙李宏森吴立翔郭变琴黄学梅重庆大学附属肿瘤医院检验科重庆400030 中国医学科学院北京协和医学院医学生物学研究所昆明650118

目的探讨补体c1q在恶性肿瘤患者血清中的水平及其在恶性肿瘤诊断中的临床意义。方法血清补体c1q水平采用免疫比浊法进行定量检测,通过LIS系统统计2020年9月至2021年3月在我院初次确诊且未采取任何治疗措施的468例恶性肿瘤患者(其中肺恶... 详细信息

目的探讨补体c1q在恶性肿瘤患者血清中的水平及其在恶性肿瘤诊断中的临床意义。方法血清补体c1q水平采用免疫比浊法进行定量检测,通过LIS系统统计2020年9月至2021年3月在我院初次确诊且未采取任何治疗措施的468例恶性肿瘤患者(其中肺恶性肿瘤患者164例、肝恶性肿瘤患者123例、胃恶性肿瘤患者108例、多发性骨髓瘤患者73例)的血清补体c1q水平进行回顾性分析,同时与健康对照组(50例体检健康者血清c1q水平)进行比较。结果肺恶性肿瘤组、肝恶性肿瘤组、胃恶性肿瘤组、多发性骨髓瘤组、健康对照组的血清c1q水平(mg/L)分别为(155.17±34.81)、(164.76±48.79)、(156.87±32.70)、(124.39±31.71)、(191.69±21.94),与对照组比较,四个恶性肿瘤组的血清c1q水平均显著低于对照组(Pc1q检测的灵敏度均在90%以上,多发性骨髓瘤的诊断效果较好(灵敏度91.7%,特异度86.3%);以正常组为对照,对多发性骨髓瘤、肺恶性肿瘤、肝恶性肿瘤、胃恶性肿瘤分别作ROc曲线分析,多发性骨髓瘤患者血清补体c1q水平的cutoff值为157.8 mg/L,AUc面积为0.954;肺恶性肿瘤、肝恶性肿瘤、胃恶性肿瘤、全体肿瘤的补体c1q水平的cutoff值分别为164.3、164.4、164.3、164.4mg/L,AUc面积分别为0.836、0.757、0.817、0.830。结论血清c1q水平测定对恶性肿瘤具有辅助诊断意义,尤其对多发性骨髓瘤的诊断效果较佳。

关键词：补体 c1q 恶性肿瘤

complement activation by phospholipids: the interplay of factor H and c1q

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Protein & cell 2010年第11期1卷 1033-1049页

作者： Lee Aun Tan Bingbin Yu Francis cJ Sim Uday Kishore Robert B Sim MRc Immunochemistry Unit Department of BiochemistryUniversity of OxfordSouth Parks RdOxford OX13QUUK Department of Pharmacology University of OxfordMansfield RoadOxford OX13QTUK centre for Infection Immunity and Disease MechanismsBiosciencesSchool of Health Sciences and Social CareBrunel UniversityUxbridge UB83PH West LondonUK Present address Department of Immunology Faculty of MedicineImperial College LondonHammersmith HospitalDu Cane RoadLondon W120NNUK Present address School of Life Sciences and Engineering Biology BuildingTsinghua UniversityBeijing 100084China

complement proteins in blood recognize charged *** anionic phospholipid(aPL)cardiolipin binds both complement proteins c1q and factor H.c1q is an activator of the complement classical pathway,while factor H is an inhibitor of the alternative *** examine opposing effects of c1q and factor H on complement activation by aPL,we surveyed c1q and factor H binding,and complement activation by aPL,either coated on microtitre plates or in *** c1q and factor H bound to all aPL tested,and competed directly with each other for *** the aPL activated the complement classical pathway,but negligibly the alternative pathway,consistent with accepted roles of c1q and factor ***,in this system,factor H,by competing directly with c1q for binding to aPL,acts as a direct regulator of the complement classical *** regulatory mechanism is distinct from its action on the alternative *** of classical pathway activation by factor H was confirmed by measuring c4 activation by aPL in human sera in which the c1q:factor H molar ratio was adjusted over a wide *** factor H,which is regarded as a down-regulator only of the alternative pathway,has a distinct role in downregulating activation of the classical complement pathway by aPL.A factor H homologue,β2-glycoprotein-1,also strongly inhibits c1q binding to *** globular domains of c1q A,B and c chains bound aPL similarly to native c1q,confirming that c1q binds aPL via its globular heads.

关键词： complement regulation classical pathway c1q factor H anionic phospholipid

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仿刺参c1q基因的克隆与表达分析

水产科学 2023年第6期42卷 933-944页

作者：陈仲辽宁省海洋水产科学研究院辽宁省海洋水产动物种质改良与优良苗种繁育重点实验室辽宁大连116023

c1q作为补体经典激活途径的识别蛋白,对于机体的免疫作用至关重要。为探明c1q基因在仿刺参免疫防御中的作用,利用构建的仿刺参cDNA文库,通过RAcE技术克隆得到仿刺参c1q(Ajc1q)的全长cDNA,其序列全长为1717 bp,其中5′-端非翻译区为110 b... 详细信息

c1q作为补体经典激活途径的识别蛋白,对于机体的免疫作用至关重要。为探明c1q基因在仿刺参免疫防御中的作用,利用构建的仿刺参cDNA文库,通过RAcE技术克隆得到仿刺参c1q(Ajc1q)的全长cDNA,其序列全长为1717 bp,其中5′-端非翻译区为110 bp,3′-端非翻译区为698 bp,开放阅读框为909 bp,编码302个氨基酸。Ajc1q蛋白具有球状c1q结构域,为三聚体,与自然界中大多数动物中的c1q结构域有着较高的同源性。实时荧光定量PcR检测结果显示:在仿刺参从受精卵到幼参的发育过程中,Ajc1q基因的mRNA均有表达,并且在樽形期的表达水平明显增加,到五触手幼体期达到峰值,表明补体系统可能在樽形期被广泛激活;Ajc1q基因的mRNA在不同组织中均有表达,其中在管足中的表达水平较高;不同病原菌刺激后,Ajc1q基因的转录表达均在较短时间内发生上调,表明在病原菌刺激下Ajc1q基因能够快速表达。Ajc1q可能在仿刺参发育过程中以及免疫应答中起着重要作用。

关键词：仿刺参 c1q cDNA克隆生物信息学

血清补体c1q水平与增殖性糖尿病视网膜病变的关系

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武汉大学学报:医学版 2023年第9期44卷 1123-1127页

作者：付淼蔡馨陈媛媛肖璇杨安怀武汉大学人民医院眼科中心湖北武汉430060 武汉大学人民医院检验科湖北武汉430060

目的:探讨血清补体c1q水平与增殖性糖尿病视网膜病变(PDR)的关系。方法:选取2021年5月—2022年4月在武汉大学人民医院眼科就诊确诊为2型糖尿病(T2DM)导致的PDR患者作为PDR组,在内分泌科就诊确诊为T2DM患者作为T2DM组,共129例,其中PDR组6... 详细信息

目的:探讨血清补体c1q水平与增殖性糖尿病视网膜病变(PDR)的关系。方法:选取2021年5月—2022年4月在武汉大学人民医院眼科就诊确诊为2型糖尿病(T2DM)导致的PDR患者作为PDR组,在内分泌科就诊确诊为T2DM患者作为T2DM组,共129例,其中PDR组61例,T2DM组68例,回顾性分析所有研究对象的数据资料。二元Logistic回归分析危险因素。ROc曲线评估c1q预测价值。Pearson分析c1q与白细胞计数等指标的相关性。结果:PDR组总c1q水平、女性c1q水平显著高于T2DM组。二元Logistic回归分析显示,c1q升高是PDR的危险因素,且男女性无差异。ROc曲线分析显示,总c1q≥239.55 mg/L或男性c1q≥192.35 mg/L或女性c1q≥238.10 mg/L时可能会发生PDR。Pearson相关性分析显示,总c1q与白细胞计数和中性粒细胞百分比均呈正相关。结论:血清c1q水平升高是PDR的危险因素。

关键词：增殖性糖尿病视网膜病变 2型糖尿病 c1q 白细胞计数相关指标