过敏性紫癜并肺炎支原体感染患儿免疫球蛋白和补体的研究

【摘 要】 目的 检测过敏性紫癜（HSP）合并肺炎支原体(MP) 感染的患儿血清免疫球蛋白及补体的水平,探讨MP感染与HSP的体液免疫学关系。方法 研究对象为55例HSP患儿,检测MP-IgM抗体,分为MP-IgM阳性组20例、MP-IgM阴性组35例,并以20名正常儿童作为对照组。采用全自动生化分析仪检测血清免疫球蛋白IgA、IgM、IgG、IgE及补体C3、C4。结果 HSP患儿MP感染阳性率达36.36%,合并MP感染的患儿临床症状更严重。与正常对照组相比,MP-IgM阴性组IgA、IgE明显增高（P<0.01）,C3水平降低（P<0.05）,同时IgE明显高于MP-IgM阳性组（P<0.01）,IgG、IgM、C4无明显变化。MP-IgM阳性组与正常对照组相比,IgA增高,IgM、C3、C4水平降低,且其中IgM、C3低于MP-IgM阴性组,差异均有统计学意义（P<0.05）,而IgG、IgE水平无明显改变。结论 在HSP儿童中有较高MP感染率,所有HSP患儿存在血清IgA增高及C3水平降低,说明体液免疫参与HSP的发病。伴MP感染的HSP患儿体液免疫功能更加紊乱,表现在C4水平下降,IgM、C3明显低于MP-IgM阴性组,IgE增高仅见于MP-IgM阴性组,提示MP感染的HSP患儿可能更多伴有低补体血症的自身免疫紊乱参与,说明MP感染引起的免疫紊乱可能在HSP发生、发展中具有重要作用。     

反复呼吸道感染患儿血清微量元素及体液免疫水平测定及临床意义

目的:探讨反复呼吸道感染患儿血清微量元素及体液免疫水平测定及其临床意义。方法:选取2016年1月至2017年1月在我院接受治疗的反复呼吸道感染患儿64例作为观察组,另外选取同期来我院体检的健康儿童60例作为对照组,比较两组儿童血清微量元素钙(Ca)、铁(Fe)、铜(Cu)、锌(Zn)、镁(Mg)等的水平、体液免疫因子免疫球蛋白A(IgA)、免疫球蛋白M(IgM)、免疫球蛋白G(IgG)水平及血清补体C3、C4、C5水平,并分析其相关性。结果:观察组患儿血清Ca、Fe、Zn水平显著低于对照组儿童(P0.05),两组儿童血清Cu、Mg水平比较差异无统计学意义(P0.05)。观察组患儿血清IgA、IgM、IgG水平低于对照组儿童(P0.05)。两组儿童血清补体C3、C4、C5水平比较差异无统计学意义(P0.05)。经Pearson相关性分析可得:反复呼吸道感染患儿血清Ca、Fe、Zn与血清IgA、IgM、IgG水平呈正相关(P0.05)。结论:反复呼吸道感染患儿存在血清Ca、Fe、Zn微量元素缺乏及血清IgA、IgM、IgG水平降低现象,且它们之间具有正相关关系,可能共同促进反复呼吸道感染的发生。     

炎症性肠病患者肠道菌群分布及其与炎症指标和免疫球蛋白水平的关系

目的研究炎症性肠病(inflammatory bowel disease,IBD)患者肠道菌群分布特点及其与血清髓过氧化物酶(MPO)、C反应蛋白(CRP)、免疫球蛋白表达的关系。方法选择2015年5月至2018年5月在延安市中医医院诊断治疗的65例炎症性肠病患者为观察组,另选取于本院体检的65例无消化系统疾病者作为对照组,分析两组患者肠道菌群分布特点以及血清MPO、CRP和免疫球蛋白表达情况,同时分析其相关性。结果观察组患者肠道乳杆菌(t=6.128,P<0.001)、双歧杆菌(t=14.029,P<0.001)、肠球菌(t=7.858,P<0.001)、真杆菌(t=15.220,P<0.001)水平显著低于对照组。观察组患者血清MPO(t=21.016,P<0.001)、CRP(t=58.970,P<0.001)水平显著高于对照组,IgA(t=2.967,P=0.004)、IgM(t=4.859,P<0.001)、IgG(t=19.828,P<0.001)水平显著低于对照组。相关性分析显示,IBD患者IgA、IgM、IgG水平与肠道乳杆菌、双歧杆菌、肠球菌、真杆菌数量均呈正相关,血清MPO、CRP水平与肠道乳杆菌、双歧杆菌、肠球菌、真杆菌数量均呈负相关(均P<0.05)。结论在炎症性肠病的发展中,肠道菌群与血清MPO、CRP水平及免疫球蛋白水平均具有相关性,可作为IBD患者诊断和治疗的依据。     

急性化脓性扁桃体炎患者咽部菌群特征

目的基于16S rRNA基因高通量测序技术分析急性化脓性扁桃体炎患者咽部菌群特征。方法选择2017年2月至2019年10月在我院就诊的137例急性化脓性扁桃体炎(AST)患者为AST组,选择同期我院20例体检者为对照组,每个对象于左侧扁桃体采集口咽拭子,利用16S rRNA测序技术进行高通量测序分析,并对咽拭子进行细菌培养。结果AST组患者咽部菌群Ace指数、Chao指数、Shannon指数显著低于对照组,Simpson指数显著高于对照组(P<0.05)。科水平上,AST组患者咽部葡萄球菌科和巴斯德菌科相对丰度显著增加(均P<0.05)。属水平上,AST组患者咽部葡萄球菌属、嗜血杆菌属和不动杆菌属相对丰度显著增加。细菌培养结果显示,AST组患者咽部葡萄球菌属、嗜血杆菌属和克雷伯菌属的阳性率高于对照组(均P<0.05)。结论AST患者咽部菌群与健康人相比具有一定差异。AST患者的致病菌可能隶属于葡萄球菌属、嗜血杆菌属和克雷伯菌属。     

细菌性阴道病肠道菌群与阴道菌群16S rDNA测序分析

目的通过对细菌性阴道病(BV)患者肠道菌群及阴道菌群16S rDNA扩增子测序,分析其结构、多样性、相关性以及BV对肠道菌群的影响,为今后治疗BV提供新的思路。方法选取符合纳入标准的BV患者11例(BV组),健康者9例(C组),留存阴道分泌物及新鲜粪便进行16S rDNA基因检测分析。结果C组阴道菌群以乳杆菌属为主,BV与加德纳菌属、普雷沃菌属、Sneathia、窄食单胞菌属(Stenotrophomonas)、阿托波菌属、Shuttleworthia、巨型球菌属密切相关。BV组肠道、阴道菌群丰富度均高于C组。Alpha多样性分析中C组和BV组肠道菌群、阴道菌群的Shannon指数组间比较,χ²值为29.137, P=0.000<0.05,两组阴道菌群Shannon指数组间比较差异具有统计学意义(P<0.05),BV组高于C组。物种多样性曲线反映本研究样本测序数据量的合理性,表明BV组的肠道菌群多样性、丰富度均高于C组,主坐标分析表明C组肠道与阴道的菌群结构差距较大,BV组肠道与阴道的菌群结构有相似之处,且两组肠道菌群结构接近。BV组阴道菌群中厚壁菌门丰度较C组低,放线菌门、拟杆菌门较C组高;BV组肠道菌群中拟杆菌门丰度较C组低;C组肠道中拟杆菌门明显高于阴道,厚壁菌门明显低于阴道; BV组阴道菌群中放线菌门丰度高于C组,差异均具有统计学意义(P<0.05)。结论BV阴道菌群与肠道菌群具有相关性,BV可能引起肠道菌群结构比例和多样性的改变。     

水痘-带状疱疹病毒对系统性红斑狼疮患者体液免疫功能的影响

目的:观察水痘患者、系统性红斑狼疮(systemic lupus erythematosus,SLE)患者和系统性红斑狼疮合并水痘患者体液免疫指标的变化,探讨水痘-带状疱疹病毒对系统性红斑狼疮患者体液免疫功能的影响。方法:选择在我院诊断治疗的水痘患者、系统性红斑狼疮患者和系统性红斑狼疮合并水痘患者共66例,同时设21例正常对照组;利用血液细胞分析仪检测各组血液中白细胞计数(WBC)、血小板计数(PLT)以及血红蛋白含量(HGB);采用免疫比浊法检测各组血清中免疫球蛋白G(IgG)、免疫球蛋白A(IgA)和免疫球蛋白M(IgM)以及补体C3、C4的水平。结果:与正常对照组比较,水痘组、SLE组以及SLE合并水痘组WBC、PLT和HGB含量下降,其中SLE组和SLE合并水痘组WBC、PLT降低,差异有统计学意义(P<0.05或P<0.01);水痘组血清中IgG、IgA和IgM含量下降,SLE组和SLE合并水痘组血清中IgG、IgA和IgM含量上升,其中水痘组血清中IgA含量减少有统计学意义(P<0.05),SLE组和SLE合并水痘组血清中IgG、IgA含量增加有统计学意义(P<0.05或P<0.01);水痘组血清中补体C3、C4含量增加,SLE组和SLE合并水痘组血清中补体C3、C4含量减少,其中SLE合并水痘组减少且差异有统计学意义(P<0.05)。与SLE组比较,SLE合并水痘组WBC明显增加(P<0.05),血清中IgG、IgA和补体C3、C4降低且差异有统计学意义(P<0.05)。结论:水痘-带状疱疹病毒可引起系统性红斑狼疮患者免疫系统相关指标的改变并对其产生影响。     

中性粒细胞明胶酶相关脂质运载蛋白、尿胱抑素C水平联合检测对肾功能评价的临床意义

目的：探讨中性粒细胞明胶酶相关脂质运载蛋白、胱抑素C和免疫球蛋白水平检测在儿童过敏性紫癜（HSP）早期肾损害诊断中的应用价值及相关性。方法：将60患儿分为HSP普通型组30例、HSP肾型组30例,另随机选择同期门诊体检儿童60例为对照组,检测受试者血浆NGAL、尿胱抑素和免疫球蛋白（IgA、IgM、IgG）的水平。结果：3组患儿NGAL、胱抑素C和IgA水平比较,差异有统计学意义（P〈0．05）;3组IgM、IgG之间比较,差异无统计学意3k（P〉0．05）。HSP肾型组较NGAL、胱抑素c和IgA含量高于对照组,差异有统计学意义（x。122．4,28．3,19．7,P〈0．05）;HSP肾型组NGAL、胱抑素C和Iga含量高于HSP普通型组,差异有统计学意义（x^2=25．7,32．6,22．1,P〈0．05）。NGAL与胱抑素C呈正相关（r=12．36,P〈0．05）;NGAL与IgA呈正相关（r=17．01,P〈0．05）;胱抑素C与IgA呈正相关（r=22．25,P〈0．05）。结论：NGAL、胱抑素和免疫球蛋白水平对于HSP的诊断具有一定的价值,尤其对患儿肾功能早期损害的诊断,早期联合检测三者的水平,适时地给予预防性治疗,对保护HSP患儿的脏器功能、改善预后具有重要的临床意义。     

脓毒症患者中可溶性髓样细胞触发受体1、降钙素原、核因子κB水平与肠道菌群失调的相关性

本研究旨在探讨脓毒症患者中血清可溶性髓样细胞触发受体1(soluble myeloid cell trigger receptor 1,sTREM1)、降钙素原(procalcitonin,PCT)、核因子κB(nuclear factor­κB,NF­κB)水平与肠道菌群失衡的相关性。将2016年5月-2019年6月重庆市綦江区人民医院消化内科收治的86例脓毒症患者纳入脓毒症组,同期收治的未并发脓毒症患者50例纳入非脓毒症组,同期到本院进行体检的健康人50例纳入对照组,比较3组之间肠道菌群α多样性、肠道菌群含量,以及血清sTREM1、PCT、NF­κB水平的差异,并进行Spearman相关性分析。结果显示,脓毒症组Ace指数、Chao指数、Shannon指数显著低于非脓毒症组和对照组,Simpson指数显著高于非脓毒症组和对照组(P<0.05);脓毒症组类杆菌、双歧杆菌含量显著低于非脓毒症组和对照组,肠球菌、大肠埃希菌、葡萄球菌含量显著高于非脓毒症组和对照组(P<0.05);脓毒症组血清sTREM1、PCT、NF­κB水平显著高于非脓毒症组和对照组(P<0.05)。Spearman相关性分析显示,脓毒症患者中sTREM1、PCT、NF­κB水平与Ace指数、Chao指数、Shannon指数均呈负相关(P<0.05),与Simpson指数呈正相关(P<0.05)。结果提示,脓毒症患者中血清sTREM1、PCT、NF­κB水平与肠道菌群失衡有关联。     

免疫反应及相关细胞因子在EV71 相关手足口病 合并肺水肿中的作用

目的:探讨细胞、体液免疫应答以及相关的细胞因子在EV71相关手足口病合并肺水肿中的作用。方法:将90例经鉴定为EV71感染患儿分为手足口病合并肺水肿组38例,手足口病无并发症组52例,并设查体健康对照组28例。ELISA法检测90例EV71感染引起的手足口病患儿血清IL-6、IL-10、TNF-α及IFN-γ含量;采用流式细胞仪对血液中CD3+T、CD4+及CD8+T细胞百分比进行检测;采用免疫比浊法对90例EV71感染引起的手足口病患儿血清免疫球蛋白(IgG、IgA及IgM)及补体C3、C4含量进行检测。结果:手足口病合并肺水肿组患儿血清IL-6、IL-10及IFN-γ含量明显升高,同时伴随CD4+及CD8+T细胞百分比下降;手足口病合并肺水肿组,无并发症组及健康对照组患儿血清IgM分别为1.85±0.73,1.46±0.790和0.88±0.39,三组之间差别具有统计学意义(F=14.967,P<0.05)。而IgG与IgA在三组之间无明显变化(X2=5.535,P>0.05;F=1.988,P>0.05);手足口病患儿血清C3及C4含量均明显低于健康对照组(F=46.079;62.794,P<0.05)。结论:由IL-10及IFN-γ的异常释放而引起的广泛的中枢及外周神经系统炎症反应和T淋巴细胞衰竭是引起EV71合并肺水肿病程进展的重要原因;在EV71感染后引发的手足口病进程中存在IgM的大量释放,且伴随补体C3、C4的消耗。     

白癜风患儿抗核抗体、免疫球蛋白及补体检测的临床分析

目的:探讨白癜风患儿中抗核抗体(ANA)、免疫球蛋白(IgG、IgA、IgM)以及补体(C3、C4)的表达及临床意义。方法:收集2014年10月至2016年5月我院收治的30例白癜风患儿为病例组,并于同期随机选取30例健康体检儿童为对照组,患儿的血清ANA、12种自身抗体谱分别采用间接免疫荧光法及免疫印迹法进行检测,IgG、IgA、IgM,C3、C4水平采用免疫透射比浊法进行检测。结果:病例组中ANA阳性率为13.33%(4/30),与对照组的3.33%(1/30)比较,差异无统计学意义(P0.05)。12种自身抗体谱中,分别有1例(3.33%)患儿dsDNA、SmDNA、SS-A/Ro60KD、SS-B/La、CENP-B阳性,与对照组比较,差异均无统计学意义(P0.05)。病例组患儿血清IgG、IgA、C4水平低于对照组,差异有统计学意义(P0.05)。ANA阳性患儿血清IgG、IgA、IgM水平高于ANA阴性患儿,而补体C3、C4水平低于ANA阴性患儿,差异有统计学意义(P0.05)。结论:白癜风患儿ANA阳性表达与健康儿童无明显区别,体液免疫功能有明显异常,临床有重要的参考价值。     

Bortezomib inhibits C2C12 growth by inducing cell cycle arrest and apoptosis

Proteosome inhibitors such as bortezomib (BTZ) have been used to treat muscle wasting in animal models. However, direct effect of BTZ on skeletal muscle cells has not been reported. In the present study, our data showed that C2C12 cells exhibited a dose-dependent decrease in cell viability in response to increasing concentrations of BTZ. Consistent with the results of cell viability, Annexin V/PI analysis showed a significant increase in apoptosis after exposing the cells to BTZ for 24 h. The detection of cleaved caspase-3 further confirmed apoptosis. The apoptosis induced by BTZ was associated with reduced expression of p-ERK. Cell cycle analysis revealed that C2C12 cells underwent G2/M cell cycle arrest when incubated with BTZ for 24 h. Furthermore, BTZ inhibited formation of multinucleated myotubes. The inhibition of myotube formation was accompanied by decreased expression of Myogenin. Our data suggest that BTZ induces cell death and inhibits differentiation of C2C12 cells at clinically relevant doses.     

维生素C和酸应激对中华鳖幼鳖血清补体C3和C4含量的影响

为研究维生素C对中华鳖(Pelodiscus sinensis)血清补体C3和C4的影响及其在酸应激条件下的变化,我们设置了6个实验组,饵料中维生素C的添加量依次为0、250、500、2500、5000和10000mg／kg,喂食4周后取其血清,用透射比浊法测定酸应激前后中华鳖血清补体C3和C4的含量。结果表明,维生素C添加量为250mg／kg时,血清补体C3的含量与对照组间没有明显不同;维生素C添加量为500、2500、5000和10000mg／kg的4组,血清补体C3的含量明显高于对照组和维生素C添加量为250mg／kg组;维生素C添加量为500mg／kg的一组,血清补体CA含量明显高于其它5组;维生素C添加量为250mg／kg组明显高于10000mg／kg组。酸应激后,补体C3的含量没有明显下降,将维生素C添加量为0、250和500mg／kg的三组并为一组处理,则应激后有明显下降。维生素C添加量为0、250和500mg／kg的3组,血清补体CA的含量在酸应激后明显下降,而维生素C添加量为2500、5000和10000mg／kg的3组,应激后血清补体C4没有明显变化。维生素C和酸应激对中华鳖血清补体C3和CA含量的影响没有交互作用。这说明,维生素C在一定剂量范围内,能提高中华鳖血清补体C3和CA的水平,酸应激能导致其含量降低,而高剂量的维生素C对其下降有颉颃作用[动物学报49(6)：769～774,2003]。     

Zinc Modulates the Interaction of Protein C and Activated Protein C with Endothelial Cell Protein C Receptor

Zinc is an essential trace element for human nutrition and is critical to the structure, stability, and function of many proteins. Zinc ions were shown to enhance activation of the intrinsic pathway of coagulation but down-regulate the extrinsic pathway of coagulation. The protein C pathway plays a key role in blood coagulation and inflammation. At present there is no information on whether zinc modulates the protein C pathway. In the present study we found that Zn²⁺ enhanced the binding of protein C/activated protein C (APC) to endothelial cell protein C receptor (EPCR) on endothelial cells. Binding kinetics revealed that Zn²⁺ increased the binding affinities of protein C/APC to EPCR. Equilibrium dialysis with ⁶⁵Zn²⁺ revealed that Zn²⁺ bound to the Gla domain as well as sites outside of the Gla domain of protein C/APC. Intrinsic fluorescence measurements suggested that Zn²⁺ binding induces conformational changes in protein C/APC. Zn²⁺ binding to APC inhibited the amidolytic activity of APC, but the inhibition was reversed by Ca²⁺. Zn²⁺ increased the rate of APC generation on endothelial cells in the presence of physiological concentrations of Ca²⁺ but did not further enhance increased APC generation obtained in the presence of physiological concentrations of Mg²⁺ with Ca²⁺. Zn²⁺ had no effect on the anticoagulant activity of APC. Zn²⁺ enhanced APC-mediated activation of protease activated receptor 1 and p44/42 MAPK. Overall, our data show that Zn²⁺ binds to protein C/APC, which results in conformational changes in protein C/APC that favor their binding to EPCR.     

Generation of an antibody with a designed specificity difference for protein C and activated protein C

Rabbit polyclonal antibodies to a synthetic peptide, NH₂-Asp-Thr-Asn-Gln-Val-Asp-Gln-Lys-Asp-Gln-Leu-Asp-Phe-Arg-CONH₂ (APep), have been produced. This sequence is identical to that contained in the tetradecapeptide released from bovine protein C (PC) as a result of its conversion to its activated form (APC), except that Phe₁₃ replaced the normal Pro₁₃, in order to discourage cross-reactivity of antibodies to the carboxylterminal portion of APep with PC. The antibody pool obtained reacted with PC and showed virtually no cross-reactivity toward either APC or several typical plasma proteins. This general approach should serve well as a means of production of antibodies with a designed specificity capable of distinguishing between forms of the same protein that arise by release of peptide material.     

人Sema4C重组腺病毒载体的构建及其在小鼠成肌细胞系C2C12中的表达

利用Ad5腺病毒载体系统构建人Sema4C基因重组腺病毒表达载体并在成肌细胞系C2C12中表达,并初步探讨Sema4C基因在成肌发育过程中的可能作用。利用脂质体介导重组腺病毒载体转染HEK293细胞,包装出完整的腺病毒;将重组腺病毒载体感染C2C12成肌细胞后,利用激光共聚焦显微镜观察发现12h即有绿色荧光表达,24h后绿色荧光蛋白表达最强;流式细胞仪检测病毒的感染效率几乎达100%。WB检测结果表明感染重组腺病毒载体组C2C12细胞Sema4C蛋白的表达量明显高于空载体对照组（P<0.01）。为了进一步观察Sema4C基因对C2C12细胞增殖分化的影响,流式细胞仪检测了病毒感染48h后C2C12细胞的增殖指数,并对感染后诱导分化的C2C12细胞的分化情况进行了观察。我们的结果首次表明,过表达外源性人Sema4C基因不仅能使C2C12细胞的G0/G1期比例增加,细胞的增殖指数下降,同时在分化培养条件下还能促进C2C12细胞肌管的形成。     

SVCT与维生素C内稳态的保持

维生素C(又名抗坏血酸)是一种基本的微量营养素,作为辅助因子参与多个酶促反应,同时还是一种自由基清除剂。维生素C内稳态主要由两种钠离子依赖的维生素C转运蛋白(sodium-dependent vitamin C transporter,SVCT)——SVCT1和SVCT2来保持。SVCT1在内皮系统表达,介导了维生素C的肠吸收和肾脏重吸收;而SVCT2表达广泛,表达于脑、骨骼和其他组织,保护这些组织免遭氧化损伤。SVCT的遗传多态性与癌症的发生密切相关。对SVCT介导的维生素C内稳态的保持机制的研究,可使维生素C更好地应用于临床。     

Neutraligands of C5a can potentially occlude the interaction of C5a with the complement receptors C5aR1 and C5aR2

The complement system is central to the rapid immune response witnessed in vertebrates and invertebrates, which plays a crucial role in physiology and pathophysiology. Complement activation fuels the proteolytic cascade, which produces several complement fragments that interacts with a distinct set of complement receptors. Among all the complement fragments, C5a is one of the most potent anaphylatoxins, which exerts solid pro-inflammatory responses in a myriad of tissues by binding to the complement receptors such as C5aR1 (CD88, C5aR) and C5aR2 (GPR77, C5L2), which are part of the rhodopsin subfamily of G-protein coupled receptors. In terms of signaling cascade, recruitment of C5aR1 or C5aR2 by C5a triggers the association of either G-proteins or β-arrestins, providing a protective response under normal physiological conditions and a destructive response under pathophysiological conditions. As a result, both deficiency and unregulated activation of the complement lead to clinical conditions that require therapeutic intervention. Indeed, complement therapeutics targeting either the complement fragments or the complement receptors are being actively pursued by both industry and academia. In this context, the model structural complex of C5a–C5aR1 interactions, followed by a biophysical evaluation of the model complex, has been elaborated on earlier. In addition, through the drug repurposing strategy, we have shown that small molecule drugs such as raloxifene and prednisone may act as neutraligands of C5a by effectively binding to C5a and altering its biologically active molecular conformation. Very recently, structural models illustrating the intermolecular interaction of C5a with C5aR2 have also been elaborated by our group. In the current study, we provide the biophysical validation of the C5a-C5aR2 model complex by recruiting major synthetic peptide fragments of C5aR2 against C5a. In addition, the ability of the selected neutraligands to hinder the interaction of C5a with the peptide fragments derived from both C5aR1 and C5aR2 has also been explored. Overall, the computational and experimental data provided in the current study supports the idea that small molecule drugs targeting C5a can potentially neutralize C5a's ability to interact effectively with its cognate complement receptors, which can be beneficial in modulating the destructive signaling response of C5a under pathological conditions.     

Structure and characterization of a high affinity C5a monoclonal antibody that blocks binding to C5aR1 and C5aR2 receptors

C5a is a potent anaphylatoxin that modulates inflammation through the C5aR1 and C5aR2 receptors. The molecular interactions between C5a–C5aR1 receptor are well defined, whereas C5a–C5aR2 receptor interactions are poorly understood. Here, we describe the generation of a human antibody, MEDI7814, that neutralizes C5a and C5adesArg binding to the C5aR1 and C5aR2 receptors, without affecting complement–mediated bacterial cell killing. Unlike other anti–C5a mAbs described, this antibody has been shown to inhibit the effects of C5a by blocking C5a binding to both C5aR1 and C5aR2 receptors. The crystal structure of the antibody in complex with human C5a reveals a discontinuous epitope of 22 amino acids. This is the first time the epitope for an antibody that blocks C5aR1 and C5aR2 receptors has been described, and this work provides a basis for molecular studies aimed at further understanding the C5a–C5aR2 receptor interaction. MEDI7814 has therapeutic potential for the treatment of acute inflammatory conditions in which both C5a receptors may mediate inflammation, such as sepsis or renal ischemia–reperfusion injury.