DimerDimerIt has different meanings in different fields, but basicallymeaningBoth indicate that the same or the same kind of substances, appearing in pairs, may have properties or functions that are not available in a single state.
In chemistry, two molecules combine to form a new substance, whether it is physical action orChemical change, can be called dimer.Common examples include dimerizationCuprous chloride, Dimer aluminum chlorideDivinyl ketone, gaseous dimerizationcarboxylic acid、Dimeric cyclopentadiene, dimerCyclobutadienewait.It can be a special case of polymer, for example, sucrose consists of glucose and fructose unitscondensationAlthough sucrose is a molecule, it still belongs to a dimer.
The dimers discussed in biochemistry and molecular biology are usually observable polymers like proteins, nucleic acids, etc. In the process of formation, if two subunits are the same, they are calledHomodimer(homo -), which is called heterodimer (hetero -) if it is composed of different monomers.What are the two bodies discussed in biochemistrycovalent bondFor mode linking, disulfide bonds are usually used to link monomers, but most of them are not combined by covalent bonds, such asribosome。Another examplePyrimidine dimer, through ultraviolet radiation, DNA orRNAThe adjacent pyrimidines in the upper part of the cell are bound together by covalent bonds, which is the main reason for the biological effect of ultraviolet radiation.Restoring enzymaticCatalysisAfter absorbing light, it will return to monomer.
It is of great significance for the diagnosis and treatment of fibrinolytic system diseases (such as DIC, various thrombi) and diseases related to fibrinolytic system (such as tumor, pregnancy syndrome), as well as the monitoring of thrombolytic therapy.
Fibrin degradation productsThe increase of D level indicates that there is frequent fibrin degradation process in the body.Therefore, the fiber dimer isDeep vein thrombosis(DVT), pulmonary embolism (PE), and disseminated intravascular coagulation (DIC).
Clinical application:
Diagnosis of deep vein thrombosis (DVT)
comparative study It indicates that NycoCard D-Dimer andELISAThe consistency and sensitivity of D-Dimer in the negative diagnosis of deep vein thrombosis are close to 100% compared with phlebography.andlatexThe sensitivity of the method is only 73%, and the consistency of the results is 78%.
NycoCard D-Dimer，It is an important tool for early diagnosis and positive exclusion of DVT.Simple, fast and cost saving.
□ Pulmonary embolism (PE) and arteryThromboembolismDiagnosis of
□ Diagnosis of disseminated intravascular coagulation (DIC)
□FibrinolysisEarly test of mechanism of action Pre thrombotic risk assessment
□ Monitoring of thrombosis process and thrombolytic therapy
□ Tumor auxiliary diagnosis
advantage
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Dimer can be used as a quantitative monitoring indicator of thrombolytic effect, while FDP (fibrinolytic protein/original degradation product) can be obtained fromFibrinogenAnd also increased in primary fibrinolysis.Therefore, the latter cannot be used as a quantitative indicator of thrombolytic effect.However, the dimer immunofiltration method for gold latex coloration is based on the fact that it can be used to detect the dimer fragments of various complexes, such asFibrinolysisThe X fragment complex dimer of protein is sensitive, so the specificity of the test is reduced.The practical clinical significance of this assay in quantitative detection still needs to be proved by more clinical practice data.
Dimer or FDP determination can be used as auxiliary diagnosis for some diseases with enhanced lysosomal activity, such as DVT, DICrenal function, failure and thrombolytic effect judgment.Theoretically, DIC indicates that the small fragments formed by fibrinolysis are not sensitive to FDP detection, while the dimer test is more sensitive.Therefore, the sensitivity of a specific measurement method in post disease remains to be determined by clinical data.
The dimer can use hemagglutination sample (plasma), while FDP can use serum sample.The latter is affected by whether the serum preparation is complete.
FDP latex particle method completed the test in 3 minutes, and dimer colloidal gold immunofiltration method completed the test in 2 minutes.The former is semi quantitative determination, and the latter can be compared with ELISA if a reader is used.
Determination method
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Latex agglutination
Principle: The dimer in the tested plasma interacts with the monoclonal antibody coated on the latex particles to produce flocculentPrecipitation reaction。
Advantages: fast
Disadvantages:Qualitative experiment;SemiquantitativeThe determination requires multiple dilution of the reagent, and the repeatability of the results is poor.
Enzyme linked immunosorbent assay (ELISA)
Principle: the antigen established by two monoclonal antibodies against dimer is used as the center, two antibody sandwich methods are used, andhorseradishPeroxidase substrate asChromogenic reaction。
Disadvantages: (1) Antibodies andfibrinThe D fragment of (original) has partial reaction.Generally, D segment has an antibody binding site, so it no longer binds to the antibody with chromogenic substance, but sometimes the hook phenomenon interferes with the experimental results.
(2) The operation steps are complex and time-consuming,Antigen antibody reactionAffected by temperature and time.
(3) The standard curve is required for each experiment, so a batch of samples should be kept for simultaneous determination, which is not applicable to the needs of timely diagnosis and treatment of clinical patients.
NycoCard dimer determination
Principle: immune filtrationcolloidThe gold color reaction method uses the homoantibody sandwich, that is, the coated antibody captures the antigen (dimer) in the plasma, and addscouplingThe same antibody with colloidal gold is colored.Therefore, the antigen is also the center, and the antibody is the two sides of the sandwich, but it is the same antibody.Due to antibodySpecificityHigh, it can be combined with a variety of dimer containing fragments to increase the test sensitivity.Although it can be combined with D segment occasionally, there is no hook phenomenon.
Advantages: rapid (2min) quantitative detection, high sensitivity
No hook, not soluble at high temperature
Disadvantages: low specificity
Interference by lipid particles
The visual colorimetry is not credible, but the results of the reader are comparable with those of the ETISA.
The diagnostic value of dimer in deep vein thrombosis, in fact, dimer is not onlyDeep vein thrombosisIt is of great value and also of great significance in other diseases. Of course, the understanding of this meaning is inseparable from the understanding of dimers.
Formation of dimer
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During coagulation, thrombin causes fibrinogenhydrolysis, release fibrin FPA and FPB, and then form fibrinMonomer(SFM), the formation of ε (- γ) between SFMY chainsglutamine）- Lysine is cross-linked to form fibrin.This kind ofCovalent crosslinkingIt is the structural foundation of DD.In the dissolution process of cross-linked fibrin, X ', Y', D ', E' and other fragments are released, and DD, DD/E, YD/YD, YY/DD and other complexes are formed.These fragments are further degraded into the smallest fragment DD and DD/E complex. The molecular weight of DD is about 62000D, the half-life in vivo is>3h, and it is mainly excreted by the kidney (1, 2).Therefore, it can be used as a hingeFibrinolysisThe single chain D can be derived from fibrinogen and fibrin without hinge.There are manymonoclonal antibodyD, which can distinguish dimer from monomer, can monitor fibrin degradation products in the presence of fibrinogen.These anti dimer antibodies can detect not only free dimers, but also polymerized D domains in large fibrin complexes, including hinge fibrin complexes formed early in the coagulation process.The detection of dimer antigen can therefore detect intravascular coagulation early.Many trials have shown that low levels of dimer can rule out venous thrombosis orPulmonary embolism。The elevated dimer may beVenous thrombosisSexual diseases may also be caused by other reasons, resulting in the formation of fibrin inside and outside the blood vessels.
The most widely used tests mainly include: enzyme-linked immunosorbent assay (ELISA), latex particle agglutination test（LATEX）Immunofiltration colloidal gold staining, double antibody RBC agglutination and radioimmunoassay.The most commonly used clinical methods are ELISA, LATEX and immunofiltration colloidal gold staining, in which LATEX is faster, but less sensitive than ELISA;ELISA is highly sensitive, but it takes a long time to detect (3, 4).Because different detection methods have different sensitivities, their normal reference values vary with different detection methods and increase with age (2).
