CN104459129A - Diagnostic kit for distinguishing active and latent mycobacterium tuberculosis infection - Google Patents
Diagnostic kit for distinguishing active and latent mycobacterium tuberculosis infection Download PDFInfo
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Abstract
The invention provides a diagnostic kit for distinguishing active and latent mycobacterium tuberculosis infection with cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) serving as a diagnosis marker and a method for distinguishing active and latent mycobacterium tuberculosis infection by means of the diagnostic kit. The diagnostic kit comprises a CTLA-4, CD3, CD4, CD25, FoxP3 fluorescent antibody, erythrocyte lysate, membrane breaking liquid, washing buffer, phosphate buffer, fetal calf serum, stationary liquid and a streaming pipe. The diagnostic kit can be used for detecting the CTLA-4 expression quantity of peripheral venous blood of a patient and distinguishing active and latent mycobacterium tuberculosis infection, sensitivity and accuracy are high, and a strong basis is provided for clinic differential diagnosis.
Description
Technical field
The present invention relates to biologic medical field, particularly relate to a kind of cytotoxic t lymphocyte-associated antigen 4 of CD4+CD25+FoxP3+T cell (cytotoxic T lymphocyte-associated antigen 4, CTLA-4) that utilizes differentiate the diagnostic kit of activity and latent tuberculosis mycobacterial infections and use this diagnostic kit to differentiate the method for activity and latent tuberculosis mycobacterial infections.
Background technology
Tuberculosis is the infectious diseases of serious harm human health, is the chronic infectious disease that mortality ratio is the highest in the world at present.Eighties of last century people's eighties were once once thinking and had controlled this disease, but morbidity lungy in recent years and mortality ratio in rising trend, show according in the up-to-date report of World Health Organization's tuberculosis: the average number of patients in the whole world is 1,400 ten thousand people at present, there are 880 Wan Xinfa active tuberculosis patients, 2010 annuals have the negative population of 1,100,000 HIV to die from tuberculosis, on average have 350,000 populations to die from HIV and merge tuberculosis; One has communicable tuberculosis patient and can cause 10-15 people every year and infect Much's bacillus.Tuberculosis remains and threatens one of large infectious diseases of the mankind three a few days ago, is the first lethal infection disease being only second to acquired immune deficiency syndrome (AIDS).Therefore, tuberculosis threatens still very severe to the life and health of the whole mankind.China is a tuberculosis country occurred frequently, and tuberculosis long-term hazards our people's health, and the quick growth of HIV simultaneously makes China's control lungy be faced with huge challenge.
Much's bacillus is aerobe in a kind of born of the same parents, usual elder generation enters human body by respiratory tract, then by lymphatic vessel or blood dissemination to other positions, lymphocyte, macrophage flow to infection focus position in a large number and form granuloma, constantly growth is until macrophages die in macrophage for bacterium, and bacterium is released into infection focus again.Much's bacillus and immune cell interact and mainly occur in the innate immunity and Acquired immune response two aspects in this course, and usually there will be three kinds of final results: natural immune system removes tulase, Much's bacillus a large amount of propagation in host causes active tuberculosis (Active tuberculosis, ATB) or Much's bacillus with stationary state long-term surviving in granuloma and macrophage its for a long time control by host immune response, but be not eliminated, thus cause latent tuberculosis mycobacterial infections (Latenttuberculosis infection, LTBI) state.The conservative estimation whole world about has 1/3rd about 2,000,000,000 populations to be that latent tuberculosis infects, and this part patient's lifelong development is active tuberculosis probability is 5-10%.
Diagnosis main bag tuberculin skin test (TST) the phlegm bacteriology checking (acid-fast stain smear and Much's bacillus are cultivated), histopathology biopsy etc. of current active tuberculosis.But the specificity of above-mentioned inspection method and susceptibility are all lower.In recent years, IFN-γ release experiment (IGRAs) is considered to an important breakthrough of diagnosis of tuberculosis aspect.QuantiFERON TB Gold In-Tube test (QFT-GIT) applies enzyme linked immunosorbent assay (Enzyme-linked Immuno Sorbent Assay, ELISA) method detects the IFN-γ discharged after experimenter's peripheral blood lymphocyte stimulates by Specific Antigen of Mycobacterium Tuberculosis, the antigen of mycobacterium tuberculosis that it uses is the ESAT-6 in RD1 district, the TB7.7 (Rv2654) in CFP-10 and RD11 district, it is peculiar that these antigens are Much's bacillus institute, there is not cross reaction with BCG.QFT-GIT test in October, 2007 obtain U.S. FDA approval for clinical detection tuberculosis infection, and in the updated Guidelines of US Centers for Disease Control and Prevention (CDC) the recommended detection method as a kind of alternative TST.
China is tuberculosis district occurred frequently, it is reported and hide that to account for crowd's ratio be 15-30% to m tuberculosis infection patient, and IFN-γ release experiment (IGRAs) cannot differentiate activity and latent tuberculosis mycobacterial infections, cannot meet clinical needs, current clinical shortage antidiastole means; Therefore antidiastole label is developed very necessary.Multinomial research shows, multiple T cell subgroup ginseng and cell factor and tuberculosis the acquired immune response, as CD4+T cell, CD8+T cell, V γ 2V δ 2+T cell and Treg cell etc.But up to the present, differentiate that activity and latent tuberculosis mycobacterial infections related biological label and method are still among exploring.
CTLA-4 is the glycoprotein of immunoglobulin superfamily, is also the important costimulatory molecules acceptor of T lymphocytic cell surface, and for the activation of T cell provides secondary signal, blocking collaboratively stimulates path.CTLA-4 is B7/CD28 family member, is mainly expressed in T cell and the regulatory T cells of activation.CTLA-4 is the molecule antagonist of CD28, with CD28 co expression in the T cell activated, the two antigen presenting cell (APC) part combined is identical, be B7 (CD80/86), CTLA-4 stops the transmission of costimulatory signal by combination that is competitive and B7 molecule, suppress the Proliferative Activated of antigenspecific T lymphocyte, thus play the effect of Immunosuppression reaction and inducing immune tolerance.CTLA-4 is confirmed in autoimmune disease effect, and its polymorphism is relevant to the neurological susceptibility of various autoimmune disease, comprises diabetes, thyroiditis, multiple sclerosis etc.CTLA-4 molecule participates in the immune response of active tuberculosis, the expression of CTLA-4 molecule in T cell and the difference of gene pleiomorphism in active tuberculosis mycobacterial infections and healthy population thereof have correlative study, but both at home and abroad without correlative study in activity and latent tuberculosis mycobacterial infections crowd.
Summary of the invention
The present invention solves the aforementioned problems in the prior proposition, its objective is and provides one to utilize CTLA-4 differentiate activity and latent tuberculosis mycobacterial infections diagnostic kit and use this diagnostic kit to differentiate activity and latent tuberculosis mycobacterial infections method.
For achieving the above object, the present invention is by the following technical solutions:
One utilizes CTLA-4 to differentiate activity and latent tuberculosis mycobacterial infections diagnostic kit, it is characterized in that, this diagnostic kit comprises CTLA-4, CD3, CD4, CD25, FoxP3 fluorescence antibody and isotype control Ab, using the diagnostic marker as discriminating activity and latent tuberculosis mycobacterial infections.
Preferably, described diagnostic kit also comprises erythrocyte cracked liquid, rupture of membranes liquid, lavation buffer solution, immobile liquid and streaming pipe etc.
Preferably, one or more in described damping fluid hyclone, phosphate buffer, formalin, bSA, EDTA, sodium bicarbonate, ammonium chloride.
Preferably, described erythrocyte cracked liquid comprises one or more in EDTA, sodium bicarbonate, ammonium chloride; Described lavation buffer solution be phosphate, hyclone one or more; Described lavation buffer solution comprise phosphate, one or more in hyclone, distilled water.
Preferably, described diagnostic kit also comprises streaming Dyeing pipe.
Application such as above-mentioned diagnostic kit differentiates a method for activity and latent tuberculosis mycobacterial infections, and it is characterized in that, the method comprises the following steps:
Step (1), collection detection in peripheral blood of patients underwent: with EDTA anticoagulant blood-collecting pipe under aseptic condition, gather 2ml peripheric venous blood;
The detection of CTLA-4 in step (2), peripheric venous blood: with CTLA-4, CD3, CD4, CD25, FoxP3 streaming fluorescence antibody as described in claim 1,2 and isotype control Ab, detects CTLA-4 expression in detection in peripheral blood of patients underwent.
Preferably, detect CTLA-4 expression in detection in peripheral blood of patients underwent in described step (2) to comprise the following steps:
1. every example detects sample and establishes Isotype control, blank (Blank) and deficient control;
2. when detecting sample, establish the fluorescently-labeled list of detection to contaminate control tube;
3. peripheric venous blood is with after erythrocyte cracked liquid splitting erythrocyte, adds fluorescence antibody and dyes;
4. the padding fluorescence antibody comprising CD3, CD4, CD25 tri-kinds of antibody dyes before broken cell film;
5. application specific flow cytometry analysis software analysis CTLA-4 expression, carries out com-parison and analysis under the positive door (Gate) of CD3, CD4, CD25 and FoxP3.
Preferably, active tuberculosis mycobacterial infections is judged as with CTLA-4 >=10.76-13.25% compartmental results, latent tuberculosis mycobacterial infections is judged as with CTLA-4 < 10.76-13.25% compartmental results, in the 65 routine samples of the present embodiment, the susceptibility of active tuberculosis mycobacterial infections is as 87.5--100.0% to use this decision method to judge, specificity is 88.0-100.0%.
More preferably, with CTLA-4 detected value be 11.36% for diagnosis dividing value, active tuberculosis mycobacterial infections is judged as with CTLA-4 >=11.36% result, latent tuberculosis mycobacterial infections is judged as with IL-31 < 11.36% result, in the 65 routine samples of the present embodiment, the susceptibility of active tuberculosis mycobacterial infections is 97.5% to use this decision method to judge, specificity is 92.0%.
A kind of said method that uses utilizes CTLA-4 to differentiate activity and latent tuberculosis mycobacterial infections diagnostic kit, and it is characterized in that, this diagnostic kit comprises CTLA-4, CD3, CD4, CD25, FoxP3 fluorescence antibody; Erythrocyte cracked liquid, rupture of membranes liquid, permwash, lavation buffer solution and streaming pipe etc.
The present invention adopts technique scheme, compared with prior art, has following technique effect:
1) adopt the present invention to detect CTLA-4 expression in detection in peripheral blood of patients underwent, can be used for the diagnosis of active tuberculosis mycobacterial infections;
2) adopt the present invention to detect CTLA-4 expression in detection in peripheral blood of patients underwent, the diagnosis of active tuberculosis has higher susceptibility and accuracy;
3) adopt the present invention to detect CTLA-4 expression in detection in peripheral blood of patients underwent, operate quick, reasonable, the diagnosis efficiency of active tuberculosis mycobacterial infections can be improved;
4) adopt the present invention to detect CTLA-4 expression in detection in peripheral blood of patients underwent, can be used for the antidiastole of activity and latent tuberculosis mycobacterial infections.
Accompanying drawing explanation
Fig. 1: detection in peripheral blood of patients underwent CD4+CD25+FoxP3+TregCTLA-4 expression streaming figure;
Fig. 2: CTLA-4 quantitative statistics result figure on CD4+CD25+FoxP3+T cell in activity and latent tuberculosis mycobacterial infections peripheric venous blood;
Fig. 3: using the expression of CTLA-4 as the ROC curve of diagnostic activities m tuberculosis infection.
Embodiment
The invention provides a kind of CTLA-4 of utilization differentiate activity and latent tuberculosis mycobacterial infections diagnostic kit and use this diagnostic kit to differentiate the method for activity and latent tuberculosis mycobacterial infections.
Carry out detailed and concrete introduction below by specific embodiment to the present invention, to make better to understand the present invention, but following embodiment does not limit the scope of the invention.
In the present embodiment, provide the diagnostic kit differentiating activity and latent tuberculosis mycobacterial infections, this diagnostic kit comprises CTLA-4, CD3, CD4, CD25, FoxP3 fluorescence antibody; Erythrocyte cracked liquid, rupture of membranes liquid, permwash, lavation buffer solution and streaming pipe etc.
In the present embodiment, label differentiates the method for activity and latent tuberculosis mycobacterial infections to use above-mentioned diagnostic kit to differentiate, the method comprises the steps:
Step 1, collection peripheric venous blood:
Collection comprises activity and latent tuberculosis mycobacterial infections detection in peripheral blood of patients underwent:
1.1 active tuberculosis infected group (ATB group): amount to selected active tuberculosis 40 example, comprising active tuberculosis 23 example, tuberculous pleurisy 17 example, active tuberculosis inclusion criteria is as follows respectively:
.
active tuberculosis group inclusion criteria:
1) 2 Sputum smears acid-fast bacilli positives and/or the Sputum culturing mycobacterium positive;
2) C-XF has active tuberculosis sign
3) have lasting low-heat, night sweat, weak, cough, expectoration, bloody sputum or spitting of blood, uncomfortable in chest, breathe hard, the clinical manifestation such as pectoralgia;
Research selected all lungers in this part close all simultaneously and state 3 conditions, and HIV antibody is negative simultaneously, gets rid of tumour, autoimmune disease and other chronic infections (as Chronic HBV/HCV infection etc.).Age more than 18 years old, and not yet accepts antituberculosis therapy or antituberculosis therapy is less than 1 week person.
.
tuberculous pleurisy group inclusion criteria:
1) pleural effusion is transudate, and common bacteria is cultivated negative, and tubercle bacillus cultivates positive or pleural effusion smear acid-fast bacilli is positive or Sputum culturing/smear acid-fast bacilli is positive;
2) pleura pathological examination meets tuberculosis;
3) clinical manifestation of tuberculous pleural effusion is met: low-heat, night sweat, weak, uncomfortable in chest, exudative pleural effusion etc. and antituberculosis therapy responder, IGRAs is positive simultaneously;
Meet 1,2 two these any one persons are for making a definite diagnosis tuberculous pleurisy patient, and meeting the 3rd person is clinical diagnosis tuberculous pleurisy patient.All patients are that HIV is negative, do not accept antituberculosis therapy or treatment is less than 1 week person.
1.2 latent tuberculosis infected group (LTBI group): this group amounts to selected patient 25 example, inclusion criteria is: infect clinical evidence without any active tuberculosis, but IFN-γ release test (IGRAs) test positive result person enters to elect as latent tuberculosis infected group LTB group.HIV antibody is negative simultaneously, gets rid of tumour, autoimmune disease and other chronic infections (as Chronic HBV/HCV infection etc.).
Apply EDTA anticoagulant blood-collecting pipe under aseptic condition and gather peripheric venous blood 2ml, should shake up gently when gathering blood, avoid blood coagulation to carry out streaming dyeing within 4 hours.
In step 2, detection in peripheral blood of patients underwent, CTLA-4 expression detects:
The diagnostic kit that the present embodiment provides is application whole blood fluidic cell surface and cell inner dyeing method, detect CTLA-4 expression in human peripheric venous blood, other type sample comprises not this kit of exemplary application such as blood plasma, serum, cells and supernatant and cerebrospinal fluid.
Prepare before step 2.1, detection:
(a). diagnostic kit is kept at 2-8 DEG C, uses erythrocyte cracked liquid, cleansing solution reagent balance to room temperature;
(b). by streaming Dyeing pipe mark pipe, comprise blank tube, Dan Ranguan, deficient control pipe, Isotype control pipe and experiment tube;
(c). lavation buffer solution A prepares: add 50ml hyclone in 950ml 1 × PBS, with 0.45 μm of Stericup suction filtration, uses front Fresh;
(d). lavation buffer solution B prepares: add 100ml 10 × lavation buffer solution 2 in 900ml ddH2O, with 0.45 μm of Stericup suction filtration
(e). add 200ml 10%Buffered Formalin, with 0.45 μm of Stericup suction filtration in immobile liquid preparation 800ml 1 × PBS
Step 2.2, CTLA-4 expression detect:
1) mark pipe, dyeing composition is as follows:
·CD3-PECy-7/CD4-FITC/C25-PE/Foxp3-APC/CTLA-4-Pacific Blue；
CD3-PECy-7/CD4-FITC/C25-PE/Foxp3-APC/CTLA-4-Pacific Blue Isotype control
Deficient control group CD3-PECy-7/CD4-FITC/C25-PE/Foxp3-APC;
The each monochromatic control tube of PECy-7, APC, Pacific Blue, FITC, PE;
Unstained blank pipe;
2) those selected heparin anti-coagulating 100 μ l chosen by each pipe, adds erythrocyte cracked liquid 2ml, and incubated at room 10-15 minute broken red, until liquid clarification;
3) centrifugal 5 minutes of 1500rpm, abandon supernatant, stay cell precipitation, vortex shakes instrument or pats mixing gently, add lavation buffer solution A 2ml to wash once (1500rpm horizontal centrifugal 5 minutes), abandon supernatant, stay cell precipitation, vortex oscillation instrument pats mixing gently, adds lavation buffer solution A 1ml and washs once (ditto) again;
4) add CD3-PECy-72.5 μ l, CD4-FITC 2.5 μ l in combination, CD25-PE 5 μ l mixes, room temperature lucifuge hatches 10 minutes;
5) often pipe adds 2ml lavation buffer solution A washing once (1500rpm horizontal centrifugal 5 minutes), and abandon supernatant, stay cell precipitation, vortex oscillation instrument pats mixing gently; Add lavation buffer solution A 1ml to wash again once (ditto);
6) often pipe adds rupture of membranes liquid 1ml, puts 4 DEG C of refrigerator lucifuges and hatches 45 minutes;
7) often pipe adds the lavation buffer solution B 1ml of dilution, and wash 2 times (1500rpm horizontal centrifugal 5 minutes), abandon supernatant, stay cell precipitation, vortex oscillation instrument pats mixing gently;
8) often pipe adds CD152 (CTLA-4)-Biotinylated 10 μ l or Isotype control 10 μ l, and mixing, puts 4 DEG C of refrigerator lucifuges and hatch 45 minutes; (note: deficient control group does not add above-mentioned antibody)
9) often pipe adds the lavation buffer solution B 1ml of dilution, and wash 2 times (1500rpm horizontal centrifugal 5 minutes), abandon supernatant, stay cell precipitation, vortex oscillation instrument pats mixing gently;
10) often pipe adds Streptavidin-Pacific Blue 1 μ l, Foxp3-APC antibody 5 μ l, and mixing, puts 4 DEG C of refrigerator lucifuges and hatch 45 minutes;
11) often pipe adds the lavation buffer solution B 1ml of dilution, and wash 2 times (1500rpm horizontal centrifugal 5 minutes), abandon supernatant, stay cell precipitation, vortex oscillation instrument pats mixing gently;
12) often pipe adds 200 μ l immobile liquid fixed cells, and add a cover, 4 DEG C keep in Dark Place to be detected;
13) flow cytomery and data analysis:
Sample after complete blood cell dyeing is carried out the detection of CD4+CD25+T cell, CD4+CD25+Foxp3+T cell and CD4+CD25+Foxp3+CTLA-4+T cell on flow cytometer.The data obtained is analyzed with FCS Express V3 software, the proportion of composing of CD3+CD4+CD25+Foxp3+CTLA-4+T cell.
The judgement of step 3, diagnostic result:
This enforcement provides one independently diagnositc decision method, carries out antidiastole according to the expression activity of CTLA-4 in detection in peripheral blood of patients underwent and latent tuberculosis mycobacterial infections.
Be judged as active tuberculosis mycobacterial infections with CTLA-4 >=10.76-13.25% compartmental results respectively, be judged as latent tuberculosis mycobacterial infections with CTLA-4 < 10.76-13.25% compartmental results.In the 65 routine samples of the present embodiment, the susceptibility of active tuberculosis mycobacterial infections is as 87.5--100.0% to use this decision method to judge, specificity is 88.0-100.0%.
Optimize with CTLA-4 detected value be 11.36% for diagnosis dividing value, be judged as active tuberculosis mycobacterial infections with CTLA-4 >=11.36% result, be judged as latent tuberculosis mycobacterial infections with CTLA-4 < 11.36% result.In the 65 routine samples of the present embodiment, the susceptibility of active tuberculosis mycobacterial infections is 97.5% to use this decision method to judge, specificity is 92.0%.
The detected value of the CTLA-4 expression that the 65 Patients with Peripheral blood samples of the present embodiment are calculated by streaming software data analysis meter is drawn in fig. 2, and shown horizontal ordinate is grouping, and ordinate is CTLA-4 expression (%).Wherein ATB (Active tuberculous) represents active tuberculosis mycobacterial infections, totally 40 examples; LTBI (latent tuberculosis infection) represents latent tuberculosis mycobacterial infections, totally 25 examples; Short-term represents median, and two groups are compared P < 0.0001, and difference has statistical significance.
Fig. 3 is the ROC curve that CTLA-4 diagnoses as active tuberculosis mycobacterial infections, and horizontal ordinate is specificity, and ordinate is susceptibility, AUC=99.1%; Wherein, ROC represents receiver operating curves, and AUC represents area under curve.
The present invention is adopted to detect CTLA-4 expression in peripheral blood in patients, can be used for the antidiastole of activity and latent tuberculosis mycobacterial infections, and having higher susceptibility and accuracy, operation simultaneously fast, can carry the diagnosis efficiency of active tuberculosis mycobacterial infections.
Be described in detail specific embodiments of the invention above, but it is just as example, the present invention is not restricted to specific embodiment described above.To those skilled in the art, any equivalent modifications that the present invention is carried out and substituting also all among category of the present invention.Therefore, equalization conversion done without departing from the spirit and scope of the invention and amendment, all should contain within the scope of the invention.
Claims (10)
1. the diagnostic kit utilizing CTLA-4 to differentiate active tuberculosis mycobacterial infections and latent tuberculosis mycobacterial infections, it is characterized in that, this diagnostic kit at least comprises CTLA-4 fluoroscopic examination antibody, as discriminating Much's bacillus activity and latent infection diagnostic marker.
2. diagnostic kit according to claim 1, it is characterized in that, described diagnostic kit also comprises one or more in erythrocyte cracked liquid, phosphate buffer, rupture of membranes liquid, permwash damping fluid, and CD3, CD4, CD25, FoxP3 fluorescence antibody and isotype control Ab.
3. diagnostic kit according to claim 2, is characterized in that, described erythrocyte cracked liquid and damping fluid comprise one or more in hyclone, phosphate buffer, formalin, bSA, EDTA, sodium bicarbonate ammonium chloride.
4. diagnostic kit according to claim 2, is characterized in that, described diagnostic marker is streaming fluorescent marker antibody.
5. diagnostic kit according to claim 1, is characterized in that, described diagnostic kit also comprises solid flow centrifugal pipe.
6. the diagnostic kit of application as described in claim 1-5 any one differentiates a method for Much's bacillus activity and latent infection, and it is characterized in that, the method comprises the following steps:
Step (1), collection detection in peripheral blood of patients underwent: with EDTA anticoagulant blood-collecting pipe under aseptic condition, gather 2ml peripheric venous blood;
The detection of CTLA-4 in step (2), peripheric venous blood: with CTLA-4, CD3, CD4, CD25, FoxP3 streaming fluorescence antibody as described in claim 1,2 and isotype control Ab, detects CTLA-4 expression in detection in peripheral blood of patients underwent.
7. method according to claim 6, is characterized in that, detects CTLA-4 expression in detection in peripheral blood of patients underwent and comprise the following steps in described step (2):
Step (2.1), every example detect sample and establish Isotype control, blank (Blank) and deficient control;
The fluorescently-labeled list of detection is established to contaminate control tube when step (2.2), detection sample;
Step (2.3), peripheric venous blood, with after erythrocyte cracked liquid splitting erythrocyte, add fluorescence antibody and dye;
Step (2.4), the padding fluorescence antibody comprising CD3, CD4, CD25 tri-kinds of antibody dye before broken cell film;
Step (2.5), application specific flow cytometry analysis software analysis CTLA-4 expression, carry out com-parison and analysis under the positive door of CD3, CD4, CD25 and FoxP3.
8. method according to claim 7, is characterized in that,
Be judged as active tuberculosis mycobacterial infections with CTLA-4 >=10.76-13.25% compartmental results, be judged as latent tuberculosis mycobacterial infections with CTLA-4 < 10.76-13.25% compartmental results.
9. method according to claim 8, is characterized in that, judge that the susceptibility of active tuberculosis mycobacterial infections is 87.5--100.0%, specificity is 88.0-100.0%.
10. method according to claim 7, is characterized in that,
With CTLA-4 detected value be 11.36% for diagnosis dividing value, active tuberculosis mycobacterial infections is judged as with CTLA-4 >=11.36% result, latent tuberculosis mycobacterial infections is judged as with IL-31 < 11.36% result, the susceptibility of active tuberculosis mycobacterial infections is 97.5% to use this decision method to judge, specificity is 92.0%.
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| CN106546737A (en) * | 2016-10-24 | 2017-03-29 | 广州迪澳医疗科技有限公司 | A kind of method of vitro detection active tuberculosis |
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| CN107449909A (en) * | 2017-07-25 | 2017-12-08 | 深圳市星系生物科技有限公司 | A kind of protein chip and kit for active tuberculosis diagnosis |
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| CN112501278A (en) * | 2020-12-03 | 2021-03-16 | 中国医学科学院病原生物学研究所 | Application of SMIM26 as tuberculosis diagnosis molecular marker |
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