[go: up one dir, main page]

WO2019109321A1 - Système de détection pour cellules immunitaires mémoires, et ses applications - Google Patents

Système de détection pour cellules immunitaires mémoires, et ses applications Download PDF

Info

Publication number
WO2019109321A1
WO2019109321A1 PCT/CN2017/115130 CN2017115130W WO2019109321A1 WO 2019109321 A1 WO2019109321 A1 WO 2019109321A1 CN 2017115130 W CN2017115130 W CN 2017115130W WO 2019109321 A1 WO2019109321 A1 WO 2019109321A1
Authority
WO
WIPO (PCT)
Prior art keywords
detection system
antigen
stimulating
detection
cells
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/CN2017/115130
Other languages
English (en)
Chinese (zh)
Inventor
高大可
陈锦河
杨翔
楼建荣
赵玉慧
谢桂华
邢智浩
王素盈
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Leide Biosciences Co Ltd
Original Assignee
Leide Biosciences Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Leide Biosciences Co Ltd filed Critical Leide Biosciences Co Ltd
Priority to PCT/CN2017/115130 priority Critical patent/WO2019109321A1/fr
Publication of WO2019109321A1 publication Critical patent/WO2019109321A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Images

Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids

Definitions

  • the invention belongs to the field of medical detection applications, and relates to a detection system of memory immune cells and an application thereof.
  • Cytokine refers to a small class of polypeptide glycoproteins that are closely related to the body's inflammation and immune response. When the body is infected with a disease, a series of related cells participate in the immune response process by coordinating the body. Taking tuberculosis immunity as an example, Mycobacterium tuberculosis induces type IV hypersensitivity through T lymphocyte mediation. The body plays a role in T cell immunity, and multiple cytokines participate in the immune response, mainly by CD4+ T cells. Helper type 1 cells (Th1) and CD8+ T cells, T helper type 2 cells (Th2), are mediated. Related cytokines include interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-10 (IL-10), interferon- ⁇ (IFN- ⁇ ), and the like.
  • IL-2 interleukin-2
  • IL-6 interleukin-6
  • IL-10 interleukin-10
  • IFN- ⁇ interferon- ⁇
  • IGRAs ⁇ -interferon release assay.
  • IGRAs are techniques for detecting the ability of T cells to produce and release gamma-interferon after stimulation with tuberculosis-specific antigens in vitro, thereby determining cell-mediated immune responses.
  • IGRAs stimulates the whole blood or peripheral blood mononuclear cells of the subject with two kinds of antigens specific to E.
  • QuantiFERON-TB Gold In-Tube QFT-GIT
  • QFT QuantiFERON-TB Gold In-Tube
  • QuantiFERON-TB Gold has been approved by the US FDA as an in vitro diagnostic for the detection of M. tuberculosis infection. It uses a mixture of analog ESAT-6, CFP-10 and TB7.7 (p4) proteins to stimulate heparinized cells in whole blood, and IFN-interferon is detected by ELISA to identify in vitro responses to these peptide antigens. The response is associated with M. tuberculosis infection.
  • QFT is the first IGRAs product approved for FDA listing and is a preferred alternative to TST in many national guidelines and recommendations.
  • QFT is a highly specific, controlled hematology test that can be used to aid in the diagnosis of TB infections and provides results to show individuals' T cell responses that are highly specific for M. tuberculosis antigens.
  • QFT uses an enzyme-linked immunosorbent assay (ELISA) to detect gamma-interferon responses in whole blood samples after incubation with TB-specific antigens.
  • ELISA enzyme-linked immunosorbent assay
  • Both QFT and QuantiFERON-TB Gold and TB-IGRA use 0.8-1.2 mL of blood for stimulation experiments.
  • QFT and QuantiFERON-TB Gold are directly collected into the stimulation tube for subsequent testing.
  • TB-IGRA is a stimulation experiment using precise blood separation of 1 mL of blood. T-Spot TB was performed after isolation of PBMC cells from 8 mL of adult blood, requiring 250,000 PBMC cells per well.
  • T-SPOT.TB and QFT-GIT detect changes in the secretion of IFN- ⁇ or the number of IFN- ⁇ secreted by memory T cells stimulated by tuberculosis antigen, thereby judging whether the body is Infected with M. tuberculosis.
  • the sensitivity of T-SPOT.TB in the diagnosis of tuberculosis is 90%, but T-SPOT.TB needs to separate human peripheral blood mononuclear cells (PBMC), which is cumbersome.
  • PBMC peripheral blood mononuclear cells
  • the QFT-GIT method is relatively easy to operate, but the sensitivity to assist in the diagnosis of tuberculosis is only 70%.
  • the sensitivity to assist in the diagnosis of tuberculosis is only 70%.
  • CN 102680684 A discloses the technical field of detection of Mycobacterium tuberculosis, in particular to a method for detecting whole blood T cells specific to tuberculosis antigen, which incubates a tuberculosis specific epitope peptide, an MHC donor and a peripheral whole blood of a subject, directly Signals for detection of complexes formed by MHC donor-Mycobacterium tuberculosis epitope-specific T cells.
  • CN 101446585A discloses an agent and method for detecting Mycobacterium tuberculosis infection in vitro, comprising the M233 polypeptide represented by SEQ ID NO.
  • the detection sample of the above detection method has a volume of 1-5 mL, and the detection sensitivity thereof needs to be further improved.
  • the present patent provides a detection system for memory immune cells and an application thereof, which can improve the sensitivity of detecting cytokines secreted by memory T cells after being stimulated again, and improve the detection of cytokines secreted by memory T cells.
  • the basic auxiliary diagnostic kit has overall sensitivity and reduces the possibility of missed detection.
  • an object of the present invention is to provide a detection system for memory immune cells, wherein the sample amount in the detection system is 0.3-0.8 mL.
  • the inventors have found that by stimulating the incubation time of the antigen, the incubation temperature, and the amount of blood to be incubated, it is found that controlling the amount of blood to be incubated can help the memory of the immune cells to be stimulated again, and the amount of secretion is significantly increased, and the amount of secretion is increased.
  • the experimental verification found that when the sample size is 0.3-0.8 mL, the sensitivity of detecting secreted substances can be significantly improved under the condition that the final concentration of the stimulating antigen is consistent.
  • the sample amount may be, for example, 0.3 mL, 0.4 mL, 0.5 mL, 0.6 mL, 0.7 mL, or 0.8 mL, preferably 0.6 mL.
  • the inventors have further found that when the sample volume is 0.6 mL, the secretion amount of the secretory substance of the memory immune cells is the highest, and the detection sensitivity is the highest.
  • the target of the detection system is a substance secreted by the cells after stimulation
  • the substance secreted by the cells after stimulation is any one of cytokines, chemokines or proteins or a combination of at least two.
  • the cytokine is a cytokine which is stimulated and secreted by immune cells and/or non-immune cells, preferably a cytokine secreted by immune cells.
  • the immune cells may be selected from, but not limited to, T cells, B cells, NK cells or macrophages, and the immune cells pass through specific cell stimulators, and after stimulation, secrete corresponding cytokines, thereby detecting whole blood.
  • the cell secretions in the test are achieved.
  • the detection system further comprises a stimulating antigen and/or a positive control antigen.
  • the stimulating antigen is a specific antigen that stimulates memory T cells.
  • the specific antigen for stimulating memory T cells is any one or a combination of at least two of a natural protein, a polypeptide, a nucleic acid, a polysaccharide, a small molecule compound, a virus-specific antigen or a bacterial-specific antigen, A bacterial specific antigen is preferred, and a Mycobacterium tuberculosis specific antigen is further preferred.
  • the natural protein, polypeptide, nucleic acid, polysaccharide, small molecule compound may be an allergen capable of stimulating a cellular response.
  • the virus-specific antigen or the bacteria-specific antigen is feasible as long as it can stimulate the antigen of the memory T cell, including the virus or bacterial surface, internal antigenic protein, nuclear protein, virus or bacterial secreted protein, and is not special here.
  • the virus-specific antigen may be, for example, a CMV virus
  • the bacterial-specific antigen may be, for example, a Mycobacterium tuberculosis-specific antigen.
  • the positive control antigen is a non-specific stimulator that stimulates immune cells.
  • the non-specific stimulating agent for stimulating immune cells is selected from, but not limited to, concanavalin A (Concanavalin A, ConA), Phytohemagglutinin (PHA), human luciferin (PWM), peanut agglutinin (PNA), soybean agglutinin (SBA), staphylococcal A protein (SAC), Any one or a combination of at least two of lipopolysaccharide (LPS) or tumor stimulating agent (PMA) is preferably phytohemagglutinin.
  • Concanavalin A ConA
  • PHA Phytohemagglutinin
  • PWM human luciferin
  • PNA peanut agglutinin
  • SBA soybean agglutinin
  • SAC staphylococcal A protein
  • Any one or a combination of at least two of lipopolysaccharide (LPS) or tumor stimulating agent (PMA) is preferably phytohemagglutinin.
  • the cytokine is cytokine which is stimulated and secreted by immune cells or non-immune cells, and can be selected by a person skilled in the art according to experimental needs.
  • the cytokines in the present invention are IL-1, IL- 2.
  • TGF- ⁇ is preferably any one of IL-2, IL-6, IFN- ⁇ , IP10 or TGF- ⁇ or a combination of at least two, and further preferably IFN - ⁇ .
  • cytokines are glycoproteins having a mass of less than 25 kDa.
  • the present application has verified that the control sample volume is 0.3-0.8 mL by verifying three cytokines such as IL-2, IL-6 and IFN- ⁇ . It does improve the detection sensitivity.
  • the detection of other cytokines is also carried out using the corresponding kit.
  • the detection system of the present application can be used for the detection of most cytokines, and the volume of the test sample is controlled to be 0.3-0.8 mL.
  • the sensitivity of the assay is further increased, and the volume of a particular sample can be fine-tuned by each cytokine by those skilled in the art.
  • the test sample is heparin anticoagulated blood.
  • the detection system further comprises detecting a stimulating antigen of the sample, the stimulating antigen being added to the sample to stimulate secretion of the cytokine for detection.
  • the detection system further comprises a conventional reagent for detecting a sample
  • the conventional reagent refers to a conventional detection reagent used for detecting a cytokine.
  • the detection of the cytokine IFN- ⁇ can be detected by using an IFN- ⁇ detection kit.
  • IL-2 can be detected by IL-2 test kit.
  • the kit is a commercially available kit.
  • the present invention provides a detection method using the detection system according to the first aspect, comprising the steps of:
  • step (2) adding a corresponding stimulating antigen to the sample of step (1), culturing;
  • the culture temperature is 30-40 ° C, for example 30 ° C, 31 ° C, 32 ° C, 33 ° C, 34 ° C, 35 ° C, 36 ° C, 37 ° C, 38 ° C, 39 ° C or 40 ° C It is preferably 35-38 ° C, and more preferably 37 ° C.
  • the culture time is 10-35 h, for example, 10 h, 11 h, 12 h, 13 h, 14 h, 15 h, 16 h, 17 h, 18 h, 19 h, 20 h, 21 h, 22 h, 23 h, 24 h, 25 h, 26 h. 27h, 28h, 29h, 30h, 31h, 32h, 33h, 34h or 35h, preferably 18-24h.
  • the invention provides the detection system of the first aspect for detecting the function of a memory immune cell.
  • the invention provides the use of a detection system according to the first aspect in the manufacture of a kit for disease detection and/or diagnosis.
  • the disease is a disease such as tuberculosis, and any disease that can be detected by detecting a secretory substance of a memory immune cell, particularly a cytokine, is feasible, and is not particularly limited herein.
  • the present invention has the following beneficial effects:
  • the detection system provided by the present invention can significantly improve the sensitivity of detecting cytokines when the final concentration of the stimulating antigen is uniform, but when the sample is reduced to 0.3-0.8 mL, compared with the conventional 1-5 mL sample. Volume, the secretion of cytokines is significantly increased, and the detection sensitivity is more than doubled, which significantly improves the sensitivity of detection and reduces the possibility of missed detection;
  • the detection system provided by the invention has a wide application range and has great market value.
  • LD represents a Mycobacterium tuberculosis-specific stimulating antigen
  • TB represents a patient number
  • FIG. 2 is a view showing the detection result of detecting INF- ⁇ by the detection system of the present invention, wherein P represents phytoagglutinin and TB represents a patient number;
  • LD Mycobacterium tuberculosis-specific stimulating antigen
  • P phytohemagglutinin
  • N represents a blank control
  • WT represents a control tuberculosis-specific stimulating antigen
  • LD represents a Mycobacterium tuberculosis-specific stimulating antigen
  • WT represents a control tuberculosis-specific stimulating antigen
  • Figure 5 is a graph showing the results of detecting the IL-2 sensitivity of a patient sample by the detection system of the present invention, wherein LD represents a Mycobacterium tuberculosis-specific stimulating antigen;
  • FIG. 6 is a diagram showing the results of detecting the IL-2 sensitivity of a healthy human sample by the detection system of the present invention, wherein LD represents a Mycobacterium tuberculosis-specific stimulating antigen;
  • Figure 7 is a graph showing the results of detecting the IL-6 sensitivity of a patient sample by the detection system of the present invention, wherein LD represents a Mycobacterium tuberculosis-specific stimulating antigen;
  • Fig. 8 is a graph showing the results of detecting the IL-6 sensitivity of a healthy human sample by the detection system of the present invention, wherein LD represents a specific stimulation resistance of Mycobacterium tuberculosis.
  • IFN- ⁇ detection kit (ELISA): Guangzhou Reid Biotechnology Co., Ltd.;
  • IGRA kit (ELISA): Wantai Biopharmaceutical Co., Ltd.;
  • Pre-preparation recruit 18-45 year old patient volunteers and healthy volunteers to collect blood samples.
  • Example 1 Effect of different volume detection samples on the detection of IFN- ⁇
  • the blood samples of the collected patients will be subjected to the following experimental steps within 4 hours:
  • step (1) mixture is placed in a 37 ° C incubator, cultured for 20 ⁇ 2h;
  • the results of the six test tubes (T) are shown in Figure 1.
  • the results of the three positive tubes (P) are shown in Figure 2.
  • the detection sensitivity first increases and then decreases.
  • the three volumes of 0.3mL, 0.6mL and 1.0mL are further compared.
  • the sensitivity of the 0.6mL volume sample is the highest. It can be seen that in the range of 0.3mL-0.6mL, the smaller the stimulated blood volume, the stimulating antigen and The stronger the stimuli stimulated by memory T cells, the stronger the IFN- ⁇ secretion.
  • Example 2 Effect of 0.6 mL and 1.0 mL Volume Detection Samples on Detection of IFN- ⁇
  • step (1) mixture is placed in a 37 ° C incubator, cultured for 20 ⁇ 2h;
  • the collected blood samples of healthy people will be subjected to the following experimental steps within 4 hours:
  • step (1) mixture is placed in a 37 ° C incubator, cultured for 20 ⁇ 2h;
  • the collected blood samples of healthy people will be subjected to the following experimental steps within 4 hours:
  • step (1) lead another set of experiments, and loosen the incubation tube cover to keep the oxygen content sufficient;
  • the plasma was aspirated and placed in a 1.5 mL EP tube, and IFN- ⁇ was detected using a gamma interferon-ELISA test kit.
  • step (1) mixture is placed in a 37 ° C incubator, cultured for 20 ⁇ 2h;
  • Fig. 5 - Fig. 6 The results of the test are shown in Fig. 5 - Fig. 6. It can be seen that under the condition that the concentration of the stimulating antigen is uniform, the 0.6 mL group is compared with the 1.0 mL group to increase the degree of response of the stimulating antigen to stimulate the memory T cells. In the patient sample, the 0.6 mL group is secreted. The content of cytokine IL-2 was significantly higher than that of the 1.0 mL group. In healthy patient samples, IL-2 was detected as 0 pg/mL.
  • Example 4 Effect of different volume test samples on IL-6 detection
  • step (1) mixture is placed in a 37 ° C incubator, cultured for 20 ⁇ 2h;
  • the results of the test are shown in Fig. 7 to Fig. 8. It can be seen that under the condition that the concentration of the stimulating antigen is uniform, the 0.6mL group is compared with the 1.0mL group to increase the degree of stimulation of the antigen-stimulated memory T cells. In the patient sample, the 0.6mL group is secreted. The content of cytokine IL-6 was significantly higher than that of the 1.0 mL group. In the healthy patient samples, the secretion of cytokine IL-6 in the 0.6 mL group was also significantly higher than that in the 1.0 mL group.
  • the detection system provided by the present invention can significantly improve the sensitivity of detecting cytokines when the final concentration of the stimulating antigen is uniform, but when the sample is reduced to 0.3-0.8 mL, compared with the conventional 1-5 mL.
  • the sample volume, the secretion of cytokines is significantly increased, and the detection sensitivity is more than doubled, which significantly improves the sensitivity of detection and reduces the possibility of missed detection; the detection system of the invention has a wide application range and has great market value.

Landscapes

  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Immunology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Molecular Biology (AREA)
  • Organic Chemistry (AREA)
  • Hematology (AREA)
  • Microbiology (AREA)
  • Zoology (AREA)
  • Urology & Nephrology (AREA)
  • Biomedical Technology (AREA)
  • Wood Science & Technology (AREA)
  • Biotechnology (AREA)
  • Physics & Mathematics (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pathology (AREA)
  • Biophysics (AREA)
  • General Physics & Mathematics (AREA)
  • Food Science & Technology (AREA)
  • Cell Biology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)

Abstract

La présente invention concerne un système de détection pour cellules immunitaires mémoires, et ses applications. La quantité d'échantillons dans le système de détection est comprise entre 0,3 ml et 0,8 ml.
PCT/CN2017/115130 2017-12-08 2017-12-08 Système de détection pour cellules immunitaires mémoires, et ses applications Ceased WO2019109321A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
PCT/CN2017/115130 WO2019109321A1 (fr) 2017-12-08 2017-12-08 Système de détection pour cellules immunitaires mémoires, et ses applications

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/CN2017/115130 WO2019109321A1 (fr) 2017-12-08 2017-12-08 Système de détection pour cellules immunitaires mémoires, et ses applications

Publications (1)

Publication Number Publication Date
WO2019109321A1 true WO2019109321A1 (fr) 2019-06-13

Family

ID=66750737

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2017/115130 Ceased WO2019109321A1 (fr) 2017-12-08 2017-12-08 Système de détection pour cellules immunitaires mémoires, et ses applications

Country Status (1)

Country Link
WO (1) WO2019109321A1 (fr)

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001079854A1 (fr) * 2000-04-13 2001-10-25 Cistem Biotechnologies Gmbh Utilisation d'une substance polycationique pour l'identification de cellules secretant des cytokines
CN102549425A (zh) * 2009-06-12 2012-07-04 疫苗技术公司 用于测量细胞介导的免疫应答的诊断试验所用的方法和组合物
CN103983785B (zh) * 2014-03-29 2015-12-30 陈仁奋 新型的特异性细胞免疫应答体外检测方法及其临床应用

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001079854A1 (fr) * 2000-04-13 2001-10-25 Cistem Biotechnologies Gmbh Utilisation d'une substance polycationique pour l'identification de cellules secretant des cytokines
CN102549425A (zh) * 2009-06-12 2012-07-04 疫苗技术公司 用于测量细胞介导的免疫应答的诊断试验所用的方法和组合物
CN103983785B (zh) * 2014-03-29 2015-12-30 陈仁奋 新型的特异性细胞免疫应答体外检测方法及其临床应用

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
RAJIV LG ET AL.: "Impact of Blood Volume, Tube Shaking, and Incubation Time on Reproducibility of QuantiFERON-TB Gold In-Tube Assay", JOURNAL OF CLINICAL MICROBIOLOGY, vol. 11, no. 51, 21 August 2013 (2013-08-21), pages 3521 - 3526, XP055614637 *

Similar Documents

Publication Publication Date Title
CN105051537B (zh) 细胞介导的免疫应答试验
US20250264458A1 (en) Method for detecting an immune cellular response
WO2024239383A1 (fr) Marqueur pour diagnostic d'infection par la tuberculose et son utilisation
CN110646619A (zh) 检测肺癌或肠癌中特异性t细胞分泌的细胞因子的方法
CN106248934A (zh) 结核分枝杆菌抗原蛋白Rv0446c及其T细胞表位肽的应用
US20200264193A1 (en) Diagnostic markers for bovine tuberculosis and uses thereof
CN106405107B (zh) 结核分枝杆菌抗原蛋白Rv2941及其T细胞表位肽的应用
CN106248935B (zh) 结核分枝杆菌抗原蛋白Rv1798及其T细胞表位肽的应用
CN108548917B (zh) 一种记忆性免疫细胞的检测体系及其应用
WO2019109321A1 (fr) Système de détection pour cellules immunitaires mémoires, et ses applications
RU2433404C1 (ru) Способ дифференциальной диагностики клещевого энцефалита, иксодового клещевого боррелиоза и их микстинфекций у детей
CN118956746A (zh) 一种培养免疫细胞的方法
CN110702918A (zh) 一种快速检测活动性结核的试剂盒
CN105759054B (zh) 一种用于检测牛布鲁菌病的elispot检测试剂盒
US20220128572A1 (en) Immunological signatures and parameters predicting therapeutic responses to anti-tnf therapy
LU500984B1 (en) Detection of Cytokines Secreted by Specific T Cells in Lung or Colorectal Cancer
CN106248936B (zh) 结核分枝杆菌抗原蛋白Rv2201及其T细胞表位肽的应用
CN112858688A (zh) Slamf7表达的cd4+t细胞在制备结核病诊断或治疗试剂中的应用
CN114859041A (zh) 结核杆菌的检测方法与试剂
CN111273024B (zh) Trem-2和/或t细胞受体在制备用于诊断活动性结核病产品中的应用
Safutri et al. IFN-γ and IL-4 secretion after stimulation of EC610 fusion antigens (ESAT-6-CFP-10) in patients with active pulmonary TB and latent TB
KR20240083054A (ko) 항원 특이적 다기능 t 림프구 분석 방법
CN106442983A (zh) 结核分枝杆菌抗原蛋白Rv3793及其T细胞表位肽的应用
KR102157770B1 (ko) 가축의 결핵 진단을 위한 항원 펩타이드 조성물 및 이의 용도
Keller et al. PPD‐Induced Monocyte Chemotactic Factor Production by Human Milk Cells

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 17934158

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 17934158

Country of ref document: EP

Kind code of ref document: A1