简介:AbstractBackground:Antiphospholipid syndrome (APS) is an autoimmune prothrombotic condition with significant morbidity. The objective of this study was to identify additional clinical and epidemiological risks of arterial thrombosis, venous thrombosis, and pregnancy morbidities in a large cohort of persistent antiphospholipid antibodies (aPLs)-positive carriers.Methods:This was a cross-sectional cohort study of 453 consecutive patients with a documented positive aPL who attended Peking University People's Hospital. Among 453 patients screened, 297 patients had persistent positive aPL. We compared asymptomatic aPL carriers with thrombotic and obstetric APS patients. And the univariate analysis and multivariable logistic regression were used to evaluate the association between different risk factors and APS clinical manifestations. The levels of circulating markers of neutrophil extracellular traps (NETs) (cell-free DNA and citrullinated histone H3 [Cit-H3]) were assessed and compared among aPL-positive carriers with or without autoimmune disease and APS patients.Results:Additional risk factors associated with arterial thrombosis among aPL-positive carriers included: smoking (odds ratio [OR] = 6.137, 95% confidence interval [CI] = 2.408-15.637, P = 0.0001), hypertension (OR = 2.368, 95% CI = 1.249-4.491, P = 0.008), and the presence of underlying autoimmune disease (OR = 4.401, 95% CI = 2.387-8.113, P < 0.001). Additional risks associated with venous thrombosis among aPL carriers included: smoking (OR = 4.594, 95% CI = 1.681-12.553, P = 0.029) and the presence of underlying autoimmune disease (OR = 6.330, 95% CI = 3.355-11.940, P < 0.001). The presence of underlying autoimmune disease (OR = 3.301, 95% CI= 1.407-7.744, P = 0.006) is the additional risk, which demonstrated a significant association with APS pregnancy morbidity. Higher circulating levels of cell-free DNA and Cit-H3 were observed among APS patients and aPL patients with autoimmune diseases compared with those aPL carriers without underlying autoimmune diseases. Furthermore, control neutrophils that are conditioned with APS patients' sera have more pronounced NET release compared with those treated with aPL carriers' sera without underlying autoimmune diseases.Conclusions:We identified several potential additional risk factors for APS clinical manifestations among a large cohort of Chinese aPL carriers. Our data may help physicians to risk stratify aPL-positive Asian patients.
简介:AbstractAntiphospholipid syndrome (APS) is a thromboinflammatory disease with a variety of clinical phenotypes. Primary thrombosis prophylaxis should take an individualized risk stratification approach. Moderate-intensity vitamin K antagonist such as warfarin remains the primary strategy for secondary thrombosis prophylaxis among APS patients, especially for patients with predominantly venous disease. For now, direct oral anti-coagulants should be avoided in most APS patients, especially those with history of arterial manifestations. Obstetric APS management should be tailored based on an individual patient’s antiphospholipid antibody profile, and obstetric and thrombotic history. Pharmacological agents beyond anticoagulants may be considered for the management of microthrombotic and nonthrombotic manifestations of APS, although more data are needed. A relatively recent discovery in the area of APS pathogenesis is the implication of neutrophil extracellular traps in thrombin generation and initiation of inflammatory cascades. APS is a complex thromboinflammatory disease with a broad clinical spectrum. Personalized therapy according to an individual’s unique thrombosis and obstetric risk should be advocated.
简介:IntroductionThereisnowanewwaytotreathypercholesterolemia,usingamonoclonalantibody(Evolocumab)thatbindstoandinhibitsPCSKA9.MostphysiciansknowthetermPCSK9buthavenoideawhatPCSK9standsfor(includingme).MypurposeforwritingthiseditorialistoeducatemyselfonwhatPCSK9isandwhatitdoes.MyhopeisthatIcanperhapseducatethosereadingthisdocumentaswell.
简介:Inordertoacknowledgethemulti-infectiondataofSTDpatientsandimprovetheprophylaxisandtherapyforSTDs,297patientsand30healthypeoplewereexaminedusingtheHSV-2plasmaantibody.TheresultsshowedthatallkindsofSTDpatientswereinfectedbyHSV-2indifierentratios.thehighestratiooccurringinsyphilispatients.
简介:1PURPOSOFTHESTUDYThearticle99intheSpecificRulesforEnforcingtheFrontierHealthandQuarantineLawofthePeople’sRepublicofChinahasindicatedthatthehealthandquarantineorganizationshallpreventanyforeignersufferingfromvenerealdiseasesfromenteringtheterritory.Becausetheroutineconfirmatorytestforsyphilisfluorescenttreponemalantibodyab-
简介:Objective:Toevaluatetheclinicalutilityoftestingserumanti-treponemapallidumIgMantibodyinthediagnosisofsyphilispatients.Methods:Seventy-twocasesofsyphilisweretestedforspecificIgMantibodywithELISA,andtheresultswerecomparedwithRPRandTPPA.Results:ThesensitivityofIgMantibodywas73.3%(11/15)inprimarysyphilis,88.9%(16/18)insec-ondarysyphilis,andtherewasnosignificantdiffer-encebetweenthesevalues(x^2=1.6363,P>0.10).ThesensitivityofIgMantibodyindiagnosinglatentsyphi-liswasonly26.1%(6/23),muchlowerthanthedetec-tionrateinsymptomaticearlvsvDhilis(x^2=17.6189.P<0.005).RPRandTPPAwereboth100%sensitiveinlatentandearlysymptomaticsyphilis.Twowereposi,fiveforIgMinthe16caseswhohadreceivedregulartreatments2to24monthsbeforeenrolled.Conclusions:SpecificIgMantibodydetectiondoeesnotappearsuperiortoRPRandTPPAindiagnosingprimarysyphilis.ThediagnosisoflatentsyphilisshouldmainlyrelyonRPRandTPPA,sincetherearelowtitersofIgMantibodyatthatstage.IgMantibodytestingaloneshouldnotberecommendedformonitor-ingsyphilisdevelopmentortreatmentefficacy.Fur-therstudiesshouldbeconcerned.
简介:STUDYONMETASTASISASSOCIATEDGENESCREENEDBYMONOCLONALANTIBODYHILQiTengping齐藤平;Zhangpeiji张沛基;WeiShuguang魏曙光;ChenDong陈东;LiRen李仁;W...
简介:AbstractWith the number of Coronavirus Disease 2019 (COVID-19) cases soaring worldwide and limited vaccine availability for the general population in most countries, the monoclonal antibody (mAb) remains a viable therapeutic option to treat COVID-19 disease and its complications, especially in the elderly individuals. More than 50 monoclonal antibody-related clinical trials are being conducted in different countries around the world, with few of them nearing the completion of the third and fourth phase clinical trial. In view of recent emergency use authorization (EUA) from the FDA (Food and Drug Administration) of casirivimab and imdevimab, it is of importance that mAbs, already used to treat diseases such as Ebola and respiratory syncytial virus (RSV) infection, are discussed in scientific communities. This brief review discusses the mechanism of action and updates to clinical trials of different monoclonal antibodies used to treat COVID-19, with special attention paid to SARS-CoV-2 immune response in host cells, target viral structures, and justification of developing mAbs following the approval and administration of potential effective vaccine among vulnerable populations in different countries.
简介:AhybridomacelllineSZ-39secretingmonoclonalantibodyagainstthehumangliomacellhasbeenestablishedbyafusionbetweenNS-1myelomacellsandspleencellsfrommiceimmunizedwithhumangliomacelllines.Monoclonalantibody(McAb)SZ-39wasanalyzedbyELISA,quantitativeabsorption,indirectimmunofluorescenceandABCimmunohistology.McAbSZ-39stronglyboundto9/10gliomacelllines,17/20gliomatissues,weaklyboundtoonelivercancercelllineand1/2lungcancerline,buttheydidnotbandwithothertestedhumancancerlinse.NcAbSZ-39havenocross-reactionwithlymphocyte,ABCredbloodcells,whitebloodcells,bloodplatelet,normalbonemarrowcells,fibroblastcellsand12normalhumantissues.TheresultindicatedtheantigenrecognizedbyMcAbSZ-39maybeaglioma-associatedantigen
简介:AbstractAntibody-drug conjugates (ADCs) combine the high specificity of monoclonal antibodies with the high anti-tumor activity of small molecular cytotoxic payloads. The anti-tumor activity of ADCs is mainly achieved by the direct blocking of the receptor by monoclonal antibodies, direct action and bystander effect of cytotoxic drugs, and antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity. ADCs have been used in adjuvant therapy and rescue treatment of human epidermal receptor 2 (HER2)-positive breast cancer, greatly improving the prognosis of breast cancer patients. Several ongoing clinical trials of ADC for breast cancer and other solid tumors proved the potential of ADCs will provide more promising treatment options for patients with malignant tumors. This review introduces the mechanism and latest clinical progress of ADC drugs approved for HER2-positive breast cancer to guide clinical practice and conduct research.
简介:AspecificcytotoxicagentagainstgastriccancerwasconstructedbycovalentlycouplingthericinAchaintomonoclonalartibody,MGb2.MGb2wasmodifiedbySPDPtointroducethe3-(2-pyridylthio)propionylradicalandthentreatedwithareducedAchaintogiveadisulfidelinkedconjugatethatretainedtheoriginalbindingspecificityoftheantibodymoiety.TheconjugateobtainedretainedtheactivityoftheantibodyandthebiologicalactivityoftheAchainwell.
简介:ObjectivesTocomparetheefficiencyoffourcommercialELISAkitsindetectingtype-specificHSV-2IgGantibodies.MaterialsandMethods:Atotalof125subjects,including105withgenitalulcers,and20controlswithoutanyhistoryofSTDswererecruitedfromtheSTDclinicfordetectionoftype-specificHSV-2IgGantibodywithdifferentkits.FourkindsofcommerciallyavailableELISAkits,includingQuidaHSV2IgGELISA(AifulangBiochemCo.Ltd.,Hangzhou),TORCH-HSV2IgG(JingmeiBiotechCo.Ltd.,Shanghai),Captia^TMHSV2IgG(Trinitybiotech,USA)andHerpeSelectT^TM2ELISAlgG(Focustechnologies,USA)wereusedforevaluation.WesternBlotassaywasperformedasagoldstandard.Results:ComparedtoWesternBlotresults,thesensitivityandspecificityofthekits(QuidaHSV2,TORCHHSV2,Captia^TMHSV2andHerpeSelect^TM2)were13.1%and98.4%,7.5%and100%,100%and11.1%,87.7%and96.7%,respectively.Thepositivepredictivevalue(PV)andnegativePVofthefourkitswere88.9%and54.3%,100%and55.5%,55.6%and100%,96.2%and89.2%,respectively.TheareasundertheROCcurveofthreekits(QuidaHSV2,Captia^TMHSV2andHerpeSelect^TM2)were0.885(0.822-0.948),0.825(0.747-0.902),0.974(0.950--0.998),respectivelyConclusion:TheperformanceofHerpeSelect^TM2isthebestamongthefourkits.Theresultsalsoindicatethatthecommerciallyavailablekitsfordetectionoftype-specificHSV2antibodyshouldbere-evaluatedintermsoftheirvalidity.
简介:Monoclonal(mAb)成功地被用于长期的疾病的治疗,例如癌症,发炎和有免疫力的疾病。与在抗体工程的技术进展,当有减少的immunogenicity的高亲密关系治疗学在聚光灯下面变得,小重组体抗体的开发碎裂。设计重组体抗体碎片的一种流行格式是单个链的改正变量(scFv)分子,父母抗体的VH和VL区域被一个多肽连接器一起在连接。scFv碎片保留目标特性和未经触动的抗体,和罐头的抗原绑定亲密关系被在房间从单个cDNA表示VH和VL区域的宫外的联盟者遗传上在大数量设计并且生产。由于它的更小的尺寸,scFv分子表演在肿瘤穿入改进了pharmacokinetics并且被主人免疫系统更好容忍。
简介:AbstractAntiphospholipid syndrome (APS) is a systemic autoimmune disease defined by thrombotic or obstetrical events and persistent antiphospholipid antibodies (aPLs). Chemokine-like factor-like MARVEL transmembrane domain-containing family (CMTM) is widely expressed in the immune system and may closely related to APS. This review aimed to systematically summarize the possible effects of CMTM on APS. Publications were collected from PubMed and Web of Science databases up to August 2020. CKLF, CKLFSF, CMTM, antiphospholipid syndrome, immune cells, and immune molecules were used as search criteria. Immune cells, including neutrophil, dendritic cells (DCs), T-cells, B-cells, and inflammatory cytokines, play an important role in the development of APS. Chemokine-like factor 1 (CKLF1) has a chemotactic effect on many cells and can affect the expression of inflammatory cytokines and adhesion molecules through the nuclear factor-kB (NF-kB) pathway or mitogen-activated protein kinase (MARK) pathway. CKLF1 can participate in the maturation of DCs, T lymphocyte activation, and the activation of neutrophils through the MAPK pathway. CMTM1 may act on Annexin A2 by regulating Ca2+ signaling. CMTM2 and CMTM6 are up-regulated in neutrophils of APS patients. Some CMTM family members influence the activation and accumulation of platelets. CMTM3 and CMTM7 are binding partners of B-cell linker protein (BLNK), thereby linking B cell receptor (BCR) and activating BLNK-mediated signal transduction in B cells. Moreover, CMTM3 and CMTM7 can act on DCs and B-1a cell development, respectively. CMTM may have potential effects on the development of APS by acting on immune cells and immune molecules. Thus, CMTM may act as a novel prognostic factor or immunomodulatory treatment option of APS.
简介:Topreparemonoclonalantibodyspecifictoepidermalgrowthfactorreceptor(EGFR)intracellulardomain,itsgenewasamplifiedfromtotalRNAofA431cellbyRT-PCR.ThenthegenewasclonedintoprokaryoticvectorpET30a(+).TherecombinantplasmidwastransformedintoE.ColiBL21(DE3)strainforproteinexpression.RecombinantproteinwasinducedwithIPTGandpurifiedusingNi2+-NTAagarose.Thentheanti-EGFRmonoclonalantibody(nAb)waspreparedwithclassicalhybridomatechnique.Positivecloneswereselectedusingindirectenzyme-linkedinmunoabsorbentassay(ELISA).Totally4hybridomacloneswereobtainedandthesemAbswereIgG1(3clones)andIgG2a(1clone),respectively.Theirlightchainswereallkappachains.WesternblottinganalysisandconfocalimmunofluorescenceassaysdemonstratedthatmAbscouldspecificallyrecognizeEGFRexpressingonA431carcinomacellline.ThemAbswillbeusefulinthestudyofEGFR-mediatedsignaltransduction.
简介:Hybridoma房间在抗体生产率追随者暴露显示增加到张力亢进的条件。然而,内在的机制很好没被理解。在现在的学习,我们假设激活的T房间的原子因素5(NFAT5)/tonicityenhancer绑定蛋白质(TonEBP)工作增加hybridomacells的抗体生产率。NFAT5是osmosensitive哺乳动物的抄写因素。然而,它在没在张力亢进的周围被洗的各种各样的器官的无所不在的表示建议NFAT5可以也在等渗的条件下面调整细胞生长和功能。在这研究,我们由西方的污点分析在hybridoma房间检验了表示ofNFAT5,并且发现它在张力亢进的媒介显著地增加了。为了推进,在hybridoma房间定义NFAT5的功能,RNA干扰技术习惯于down在SGB-8房间(一根hybridoma房间线)调整NFAT5的表示。在等渗的媒介,hybridoma房间的抗体生产率被NFAT5while的down规定减少细胞增殖没被影响。这里介绍的结果表明那NFAT5不仅在hybridoma房间在渗透的压力反应小径起一个重要作用而且为最佳的抗体生产率是必要的。