152 results about "Latent tuberculosis" patented technology

The invention discloses a protein characteristic spectrum of active tuberculosis in children and a method for creating the protein characteristic spectrum. The protein characteristic spectrum of the active tuberculosis in the children is obtained by comparing proteomics difference of an active tuberculosis group and a healthy control group. In addition, the invention further relates to the method for creating the protein characteristic spectrum of the active tuberculosis in the children, protein in blood plasma can be effectively identified and relatively quantified by utilizing a non-marked tandem mass spectrum technology of relative and absolute quantification, and a protein expression difference mass spectrum in the blood plasma of a patient suffering from the active tuberculosis in the children can be obtained by adopting the technology. A series of discovered proteins provide a foundation and resources for searching new more ideal markers; compared with a conventional blood plasma detection method, the method has relatively high sensitivity and specificity, and can be used for screening drugs for the active tuberculosis in the children; at the same time, a new way is provided for a mechanism for exploring occurrence and development of diseases.

The invention belongs to the field of biomedicine examination, and particularly relates to a kit and a method for detecting mycobacterium tuberculosis infection and application. The invention discloses a novel mycobacterium tuberculosis detection reagent by screening specific T cell epitope of mycobacterium tuberculosis, wherein the reagent contains polypeptide or analog thereof represented by SEQ ID No.1-10. The method detects cell factors released from T cells by using single or more SEQ ID No.1-10 polypeptides to contact the T cells of mycobacterium tuberculosis infected individuals. The method can effectively detect active tuberculosis or latent tuberculosis infection, and is free from disturbance of Bacilli Calmette Guerin (BCG) inoculation vaccines. The invention also discloses a diagnostic kit and other application based on the polypeptide and the method. Compared with the gamma interferon release experiments in the prior art, the method can obviously improve the detection rate without reducing the specificity and has high clinical application value.

The invention belongs to the biomedical detection field, in particular relates to a reagent and method used for detecting activity tuberculosis and latent tuberculosis infection; based on the genomic principle, the invention discloses a novel detection reagent for mycobacterium tuberculosis, containing protein or polypeptide which is represented by SEQ ID1-2, 4-5, 8-28; the method uses one or a plurality of SEQ ID 1-28 protein or polypeptide to contact T cells of a mycobacterium tuberculosis host, and detects cytokine released from the T cells; the method can detect the tuberculosis and latent infection effectively and is not interfered by BCG vaccine at the same time; the invention also discloses a diagnostic reagent kit and other application based on the protein or polypeptide and the method; compared with the T-SPOT of the prior art, the invention can improve detectable rate obviously under the condition that the specificity is not reduced; the reagent kit has cheap price, and the cost is 1 / 5 to 1 / 10 of that of the T-SPOT reagent, thus being beneficial to being popularized in the developing countries and poor areas.

The present invention includes methods, systems and kits for distinguishing between active and latent mycobacterium tuberculosis infection in a patient suspected of being infected with mycobacterium tuberculosis, and distinguishing such patients from uninfected individuals, the method including the steps of obtaining a gene expression dataset from a whole blood obtained sample from the patient and determining the differential expression of one or more transcriptional gene expression modules that distinguish between infected and non-infected patients, wherein the dataset demonstrates an aggregate change in the levels of polynucleotides in the one or more transcriptional gene expression modules as compared to matched non-infected patients, thereby distinguishing between active and latent mycobacterium tuberculosis infection.

Provided herein is an in vitro granuloma model and methods of its use. Methods of detecting and / or diagnosing latent tuberculosis in a subject are also provided, as are latency-specific antigens (and antibodies thereto), such as alpha-crystallin, and methods of identifying and using such molecules. Also provided are immunostimulatory compositions, for instance for use in eliciting an immune response in a subject, such as an immune response to a latent tuberculosis infection. Kits for carrying out the provided methods are also described.

The present invention relates to a method of diagnosing and monitoring various distinct presentations of tuberculosis: active tuberculosis disease, latent tuberculosis infection and recent tuberculosis infection. The rapid immune assay is based on the evaluation of the frequency of Interferon (IFN) gamma-producing antigen-specific T lymphocytes responding to selected peptide sequences from Mycobacterium tuberculosis, selected for their immunogenicity. The invention concerns also immunogenic and vaccine compositions based on these specific peptide sequences.

The invention discloses a kit for detecting active tuberculosis based on antigen-specific TNF-alpha-ELISA (enzyme linked immunosorbent assay) and an application thereof. The kit comprises an ELISA plate coating a TNF-alpha antibody, a TNF-alpha protein standard, protein liquid of ESAT-6 and CFP-10, a biotin-marked TNF-alpha antibody and avidin-marked horseradish peroxidase. By adopting the kit for detecting active tuberculosis based on TNF-alpha-ELISA, a method for distinguishing active tuberculosis infection from latent tuberculosis infection is established; the TNF-alpha released by the peripheral blood mononuclear cell under the stimulus of tuberculosis-specific antigens ESAT-6 and CFP-10 and the background TNF-alpha released by the peripheral blood mononuclear cell without stimulus are quantitatively detected through the ELISA technology, and the value of the antigen-specific TNF-alpha is obtained by subtracting the two so as to perform direct diagnosis on the active tuberculosis.

The invention provides mycobacterium tuberculosis protein Rv2693c and / or Rv1984c in development and / or designing of products capable of discrimination, diagnosis, auxiliary diagnosis, screening and / or auxiliary screening of latent tuberculosis infection. The invention further provides protein chips prepared from the two mycobacterium tuberculosis proteins. The protein chips prepared in the invention are used for detecting the levels of IgM antibodies respectively corresponding to the twp proteins in serum of a patient with latent tuberculosis infection and of a normal person, and detection results of the antibodies respectively corresponding to the three protein are analyzed together so as to determine whether an examined person suffers from latent tuberculosis infection; detection results show that optimal operating points of the protein chips provided by the invention in auxiliary diagnosis of latent tuberculosis infection have specificity of 80.3% and sensitivity of 75.6%, both higher than indexes of diagnosis of latent tuberculosis infection in the prior art.

The present invention describes compositions for both diagnostic and therapeutic applications. In one embodiment, the present invention contemplates a method of identifying an active M. tuberculosis infection. In another embodiment, the present invention contemplates a method of monitoring a M. tuberculosis infection. In yet another embodiment, the present invention contemplates a method of monitoring a patient's response to treatment for an active M. tuberculosis infection. In a further embodiment, the present invention contemplates a method of monitoring a patient's response to treatment for an active M. tuberculosis infection.

The present invention relates to a method of diagnosing and monitoring various distinct presentations of tuberculosis: active tuberculosis disease, latent tuberculosis infection and recent tuberculosis infection. The rapid immune assay is based on the evaluation of the frequency of Interferon (IFN) gamma-producing antigen-specific T lymphocytes responding to selected peptide sequences from Mycobacterium tuberculosis, selected for their immunogenicity. The invention concerns also immunogenic and vaccine compositions based on these specific peptide sequences.

The invention provides 13 mycobacterium tuberculosis proteins in development and / or designing of products capable of discrimination, diagnosis, auxiliary diagnosis, screening and / or auxiliary screening of latent tuberculosis infection. The invention further provides protein chips prepared from 13 mycobacterium tuberculosis protein antigens. The protein chips prepared in the invention are used for detecting the levels of IgG antibodies respectively corresponding to the 13 protein antigens in serum of a patient with latent tuberculosis infection and of a normal person, and detection results of the antibodies respectively corresponding to the three protein are analyzed together so as to determine whether an examined person suffers from latent tuberculosis infection; detection results show that optimal operating points of the protein chips provided by the invention in auxiliary diagnosis of latent tuberculosis infection have specificity of 89.4% and sensitivity of 80.6%, both higher than indexes of diagnosis of latent tuberculosis infection in the prior art.

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.

The present invention relates to a method for diagnosing latent tuberculosis infection in a subject comprising the step i) consisting of incubating a biological sample obtained from the subject with at least one Mycobacterium tuberculosis antigen, and thereafter a step ii) consisting of quantifying in said biological sample the secretion of at least one cytokine selected from the group consisting of IL-2, IL-15, IP-10 and MIG.

The invention relates to biomarkers for diagnosing and / or monitoring tuberculosisin both immunocompetent and immunocompromised individuals, monitoring the responses of individuals to anti-mycobacterial chemotherapy, monitoring the progression of latent tuberculosis to active tuberculosis, differentiating active tuberculosis from latent tuberculosis, and from other clinical conditions that mimic tuberculosis (TB). The invention also relates to methods for diagnosing, treating and monitoring tuberculosis using said biomarkers. The above pertain in all aspects both to pulmonary and extrapulmonary Mycobacterium.tuberculosis infections, with Mycobacterium.tuberculosis being the causative organism in tuberculosis.

The invention discloses a miRNA marker for assistant diagnosis of tuberculosis and application thereof. The invention requires the protection of the application of a substance for detecting miRNAs inserum exosomes in the preparation of products used for diagnosing or assisting the diagnosis of tuberculosis patients or for diagnosing or assisting the diagnosis of active tuberculosis patients, wherein each miRNA refers to one or a combination of the following five kinds of miRNAs: miR-28-3p, miR-193b-5p, miR-370-3p, miR-1246 and miR-2110. The invention also requires the application of the substance for detecting miRNAs in serum exosomes in the preparation of products used for diagnosing or assisting the diagnosis of patients with latent tuberculosis infections, wherein each miRNA refers toone or a combination of the following three kinds of miRNAs: let-7e-5p, let-7d-5p and miR-140-5p. A foundation is laid for further development of the early rapid diagnosis technology and method for tuberculosis.

The invention discloses a biomarker for diagnosing mycobacterium tuberculosis infection. The biomarker comprises IL-2 and IL-10. The invention proves that cell factors IL-2 and IL-10 can serve as markers for tuberculosis infection diagnosis for the first time, the tuberculosis infection can be diagnosed by measuring the concentration of the IL-2 and the IL-10 after peripheral blood monouclear cells are stimulated by tuberculosis antigen, and active tuberculosis and latent tuberculosis infection are further distinguished. A tuberculosis infection blood detection reagent and a kit which are prepared on the basis of the two cell factors provide new technological basis for quick diagnosis of the active tuberculosis, have the advantages of high sensitivity, high specificity and the like, are quick in operation, reasonable and practical, and can obviously improve the diagnosis efficiency of the active tuberculosis.

The invention provides an MS4A6A gene application, and relates to the preparation of products to distinguish latent tuberculosis infection and active tuberculosis. The preferred products include the products utilizing real-time quantitative PCR or gene chip detection to distinguish the latent tuberculosis infection and the active tuberculosis. According to the experimental results, the expression of the MS4A6A gene is obviously higher in the blood of tuberculosis patients than in healthy people or latent infection crowds, and therefore, the MS4A6A gene can serve as a special marking gene for the diagnosis of tuberculosis, so as to allow the tuberculosis diagnosis to be more accurate and quicker.

The invention relates to a sample containing a tuberculosis serum characterized protein and a preparation method thereof. The sample comprises the serum of an untreated patient suffering from active tuberculosis, and the serum protein of a patient suffering from lung cancer, a patient suffering from pneumonia, a patient suffering from chronic obstructive pulmonary disease or a healthy person who is ensured to be normal by physical examination, wherein the serum protein comprises three up-regulated proteins and one down-regulated protein; the proteins exit independently or any or all of the proteins are mixed together; and the sample is suitable to be detected by using mass spectrum. The sample provides a basis for further discovering new active tuberculosis biomarkers. By using the sample, the detection of the active tuberculosis is superior to any single detection method adopted currently; a non-invasive technology for early discovery and early treatment of the active tuberculosis is provided; and therefore, a new method for reducing the infectious rate of the active tuberculosis and improving the recovery rate of the tuberculosis is provided.

A vaccine for treating or preventing the establishment of latent tuberculosis infections is provided. The vaccine comprises a recombinant mycobacterium that overexpresses the transcription factor DosR, at a level sufficient to induce production of the dosR regulon genes or proteins. A host to whom the vaccine is administered mounts an immune response to the dosR regulon proteins and is thus protected from the establishment, persistence or reactivation of latent tuberculosis.

The invention discloses application of PRDM1 as a marker for preparing a product for diagnosing active tuberculosis. Fluorescence quantitative PCR is adopted for detecting expression quantity of a PRDM1 gene in a tuberculosis patient PBMCs. A result shows that the relative expression quantity of PRDM1 in smear positive tuberculosis patients, smear negative tuberculosis patients and extrapulmonarytubereulosis patients PBMCs is remarkably lowered that that of latent tuberculosis infected persons and healthy control. A subject working characteristic curve analysis result shows that PRDM1 can distinguish active tuberculosis and latent tuberculosis infection, and becomes the diagnosis target for diagnosing the active tuberculosis.

The invention discloses a co-expression system and construction method of polyvalent bacteriophage lyase genes, a live vaccine of a carrying system and preparation and application of the live vaccine. Eukaryotic expression plasmids are used as an expression vector, and LysinA, LysinB and Holin gene segments are directionally inserted into the plasmids to simultaneously express the co-expression system of the bacteriophage lyase genes of three kinds of targeted mycobacterium tuberculosis. Mycobacterium smegmatis with good targeting property of macrophages or genetically-modified recombinant BCG is used as a live vector, the co-expression system simultaneously carrying three kinds of genes is electrically transformed into the mycobacterium smegmatis or the genetically-modified recombinant BCG, and then the recombinant therapeutic tuberculosis live vaccine is obtained through expansion in vitro. The live vaccine has a good effect on the field of curing active tuberculosis or latent tuberculosis infection caused by proliferative mycobacterium tuberculosis, dormant mycobacterium tuberculosis and drug-resistant mycobacterium tuberculosis.

The present invention is directed to a polypeptide which comprises: (i) an Rv3616c protein sequence; (ii) a variant of an Rv3616c protein sequence; or (iii) an immunogenic fragment of an Rv3616c protein sequence for use in the treatment or prevention of latent TB. In other aspects the invention is directed to associated polynucleotides, fusion proteins and methods for the treatment or prevention of latent tuberculosis.

The invention relates to biomarkers for diagnosing, monitoring and / or treating tuberculosis in both immunocompetent and immunocompromised individuals with or without co-infection with HIV, monitoring the responses of individuals to anti-myco-bacterial chemotherapy, monitoring the progression of latent tuberculosis to active tuberculosis, differentiating active tuberculosis from latent tuberculosis, and from other clinical conditions that mimic tuberculosis (TB). The invention also relates to methods for diagnosing, monitoring and / or treating tuberculosis using said biomarkers. The above pertain in all aspects both to pulmonary and extrapulmonary Mycobacterium tuberculosis infections, with Mycobacterium tuberculosis being the causative organism in tuberculosis. The invention therefore finds great utility in assisting with future drug discovery efforts for tuberculosis and also provides proxy clinical end points as well as being an effective predictor of a response to treatment.

The invention discloses application of RETN and KLK1 serving as tuberculosis detecting markers. Experiments prove that the RETN gene and the KLK1 gene have evident expression differences in normal tissue, the tissue of a person with latent tuberculosis infection (LTBI) and the tissue of a patient with tuberculosis (TB), the expression level of the RETN gene in the tissue of the patient with tuberculosis (TB) is much higher than that in the normal tissue or in the tissue of the person with latent tuberculosis infection (LTBI), and the expression level of the KLK1 gene in the tissue of the patient with tuberculosis (TB) is much lower than that in the normal tissue or in the tissue of the person with latent tuberculosis infection (LTBI). Therefore, the RETN gene and the KLK1 gene can be usedas the markers for detecting or diagnosing the tuberculosis, and the occurrence and development of the tuberculosis can be monitored.

Provided herein is an in vitro granuloma model and methods of its use. Methods of detecting and / or diagnosing latent tuberculosis in a subject are also provided, as are latency-specific antigens (and antibodies thereto), such as α-crystallin, and methods of identifying and using such molecules. Also provided are immunostimulatory compositions, for instance for use in eliciting an immune response in a subject, such as an immune response to a latent tuberculosis infection. Kits for carrying out the provided methods are also described.

The invention discloses application of PGLYRP1 protein as a marker in the diagnosis of active tuberculosis. Compared with healthy people and latent tuberculosis infected people, PGLYRP1 gene expression in PBMCs from active tuberculosis patients is significantly increased. The expression level of PGLYRP1 gene can be used to distinguish between active tuberculosis patients and tuberculosis latent infected people. The expression level of PGLYRP1 gene can be used to distinguish between active tuberculosis patients and healthy people. Therefore, the PGLYRP1 protein and / or PGLYRP1 gene can be used as markers to diagnose active tuberculosis. The invention has great application value.

The invention discloses application of SERPINGI protein used as a marker in development of a reagent for active tuberculosis diagnosis. Compared with a healthy person and a latent tuberculosis infection person, the expression quantity of an SERPINGI gene in PBMCs of an active tuberculosis patient is remarkably increased, and the expression quantity of the SERPINGI can be used for distinguishing the active tuberculosis patient and the latent tuberculosis infection person and can be used for distinguishing the active tuberculosis patient and the healthy person. Therefore, the SERPINGI protein and / or SERPINGI gene can be used as the marker in development of the reagent for the active tuberculosis diagnosis. The SERPINGI protein has an important application value.

The invention belongs to the field of biomedical examination, and concretely relates to a reagent and a method for detecting Mycobacterium tuberculosis infection, and an application of a Mycobacterium tuberculosis T cell antigen epitope polypeptide. The Mycobacterium tuberculosis detection agent disclosed in the invention is obtained through screening Mycobacterium tuberculosis specific T cell antigen epitopes, and contains a polypeptide PP4 represented by SEQ ID NO.1. The method is characterized in that the single polypeptide PP4 or a combination of the PP4 and a CE polypeptide used in T-SPOT. TB test (Oxford Immunotec, Oxford, UK) is in contact with T cells of a Mycobacterium tuberculosi-infected individual in order to detect cytokines released from the T cells. Active tuberculosis or latent tuberculosis infection can be effectively detected without the interference of BCG vaccination. The method has the characteristics of high detection sensitivity, high specificity, fast speed, and simplicity in operation, and can be used for the assisted diagnosis of pulmonary tuberculosis, extrapulmonary tuberculosis and latent infection.

The present invention provides a use of a CD157 gene for the preparation of products for distinguishing latent tuberculosis infection and active tuberculosis. The products for distinguishing latent tuberculosis infection and active tuberculosis preferably comprise products adopting real-time quantitative PCR or microarrays to determine and distinguish latent tuberculosis infection and active tuberculosis. Experiments prove that the expression level of the CD157 gene of the present invention in tuberculosis patient blood is significantly higher than that of healthy people as well as people with latent infection, so the CD157 gene can be used as a specific marker gene for diagnosis of tuberculosis, thus making tuberculosis diagnosis more accurate and faster.