Diagnostic Potential of Novel Salivary Host Biomarkers as Candidates for the Immunological Diagnosis of Tuberculosis Disease and Monitoring of Tuberculosis Treatment Response.
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Diagnostic Potential of Novel Salivary Host Biomarkers as Candidates for the Immunological Diagnosis of Tuberculosis Disease and Monitoring of Tuberculosis Treatment Response.
BACKGROUND There is an urgent need for new tools for the early diagnosis of TB disease and monitoring response to treatment, particularly in resource-limited settings. We investigated the usefulness of the host marker detected in saliva as biomarker candidates for immunological diagnosis of TB disease and monitoring treatment response.
METHOD We prospectively collected saliva samples from 51 individuals who presented with signs and symptoms suggestive of TB disease in a health center in Cape Town, South Africa, prior to the establishment of a clinical diagnosis. Patients were then classified as having tuberculosis or other respiratory diseases (ORD), using a combination of clinical findings, radiological and laboratory. We evaluate the concentration of the marker 69 in the home side a saliva sample using a multiplex cytokine platform, and assess the diagnostic potential of these markers by the receiver operator characteristic (ROC) curve analysis, and general discriminant analysis.
RESULTS Of the 51 study participants, 18 (35.4%) were diagnosed with TB disease and 12 (23.5%) were HIV-infected. Only two of the 69 markers were evaluated hosts (IL-16 and IL-23) were diagnosed with TB disease individually with an area under the ROC curve ≥0.70.
A biosignature five markers consisting of IL-1β, IL-23, ECM-1, HCC1 and fibrinogen diagnosed TB disease with a sensitivity of 88.9% (95% CI, 76.7 to 99.9%) and specificity of 89.7 % (95% CI, 60.4 to 96.6%) after a leave-one-out cross validation, regardless of their HIV infection status. biosignatures eight markers performed with a sensitivity of 100% (95% CI, 83.2 to 100%) and a specificity of 95% (95% CI, 68.1 to 99.9%) in the absence of HIV infection. In addition, the concentration of 11 markers change during the treatment, suggesting that they may be useful in monitoring response to treatment of TB.
CONCLUSION We have identified a new saliva biosignatures that may be useful in the diagnosis of TB disease and monitoring response to treatment of TB. Our findings require further validation in larger studies before it could be considered biosignatures for point-of-care screening test development.
Learning from epidemiological studies, clinical and immunology in Mycobacterium africanum to improve the current understanding of host-pathogen interactions, and for the development and evaluation of diagnostic, host-directed therapies, and vaccines for tuberculosis.
Mycobacterium africanum comprises two phylogenetic lineages in the Mycobacterium tuberculosis complex (MTBC). M. africanum first described and isolated in 1968 from Senegal sputum of patients with pulmonary tuberculosis (TB) and has been identified increasingly as an important cause of human tuberculosis, particularly prevalent in West Africa.
M. africanum limited geographical distribution, in contrast with comprehensive global distribution of other species of MTBC, requires an explanation. The available data suggest that M. africanum may also have important differences in transmission, pathogenesis and host-pathogen interactions, which may affect the evaluation of new TB intervention tools (diagnostics and vaccines) -they are being used and those under development.
Description: CRK, also known as p38, is a protein that in humans is encoded by the CRK gene. This gene is a member of an adapter protein family that binds to several tyrosine-phosphorylated proteins. It is mapped to 17p13.3. The protein participates in the Reelin signaling cascade downstream of DAB1. The product of this gene has several SH2 and SH3 domains (src-homology domains) and is involved in several signaling pathways, recruiting cytoplasmic proteins in the vicinity of tyrosine kinase through SH2-phosphotyrosine interaction. The N-terminal SH2 domain of Crk functions as a positive regulator of transformation whereas the C-terminal SH3 domain functions as a negative regulator of transformation. Two alternative transcripts encoding different isoforms with distinct biological activity have been described.
Description: This recombinant p38 antibody reacts to human p38 MAPK. It may also react to the rat and mouse protein, as predicted by immunogen homology.
Description: P38 is a member of the MAP kinase family. MAP kinases act as an integration point for multiple biochemical signals, and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation and development. This kinase is activated by various environmental stresses and proinflammatory cytokines. The activation requires its phosphorylation by MAP kinase kinases (MKKs), or its autophosphorylation triggered by the interaction of MAP3K7IP1/TAB1 protein with this kinase. The substrates of this kinase include transcription regulator ATF2, MEF2C, and MAX, cell cycle regulator CDC25B, and tumor suppressor p53, which suggest the roles of this kinase in stress related transcription and cell cycle regulation, as well as in genotoxic stress response.
Description: P38 is a member of the MAP kinase family. MAP kinases act as an integration point for multiple biochemical signals, and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation and development. This kinase is activated by various environmental stresses and proinflammatory cytokines. The activation requires its phosphorylation by MAP kinase kinases (MKKs), or its autophosphorylation triggered by the interaction of MAP3K7IP1/TAB1 protein with this kinase. The substrates of this kinase include transcription regulator ATF2, MEF2C, and MAX, cell cycle regulator CDC25B, and tumor suppressor p53, which suggest the roles of this kinase in stress related transcription and cell cycle regulation, as well as in genotoxic stress response.
Description: A polyclonal antibody for detection of p38 from Human, Mouse, Rat. This p38 antibody is for WB, IHC-P, IF, ELISA. It is affinity-purified from rabbit antiserum by affinity-chromatography using epitope-specific immunogenand is unconjugated. The antibody is produced in rabbit by using as an immunogen synthesized peptide derived from human p38 around the non-phosphorylation site of T180
Description: A polyclonal antibody for detection of p38 from Human, Mouse, Rat. This p38 antibody is for WB, IHC-P, IF, ELISA. It is affinity-purified from rabbit antiserum by affinity-chromatography using epitope-specific immunogenand is unconjugated. The antibody is produced in rabbit by using as an immunogen synthesized peptide derived from human p38 around the non-phosphorylation site of T180
Description: A polyclonal antibody for detection of p38 from Human, Mouse, Rat. This p38 antibody is for WB, IHC-P, IF, ELISA. It is affinity-purified from rabbit antiserum by affinity-chromatography using epitope-specific immunogenand is unconjugated. The antibody is produced in rabbit by using as an immunogen synthesized peptide derived from human p38 around the non-phosphorylation site of T180
Description: A polyclonal antibody for detection of p38 from Human, Mouse, Rat. This p38 antibody is for WB, IF, IHC-P, ELISA. It is affinity-purified from rabbit antiserum by affinity-chromatography using epitope-specific immunogenand is unconjugated. The antibody is produced in rabbit by using as an immunogen synthesized peptide derived from human p38 around the non-phosphorylation site of Y182
Description: A polyclonal antibody for detection of p38 from Human, Mouse, Rat. This p38 antibody is for WB, IF, IHC-P, ELISA. It is affinity-purified from rabbit antiserum by affinity-chromatography using epitope-specific immunogenand is unconjugated. The antibody is produced in rabbit by using as an immunogen synthesized peptide derived from human p38 around the non-phosphorylation site of Y182
Description: A polyclonal antibody for detection of p38 from Human, Mouse, Rat. This p38 antibody is for WB, IF, IHC-P, ELISA. It is affinity-purified from rabbit antiserum by affinity-chromatography using epitope-specific immunogenand is unconjugated. The antibody is produced in rabbit by using as an immunogen synthesized peptide derived from human p38 around the non-phosphorylation site of Y182
Description: A polyclonal antibody for detection of p38 from Human, Mouse, Rat. This p38 antibody is for WB, IHC-P, ELISA. It is affinity-purified from rabbit antiserum by affinity-chromatography using epitope-specific immunogenand is unconjugated. The antibody is produced in rabbit by using as an immunogen synthesized peptide derived from human p38 around the non-phosphorylation site of T180/Y182
Description: A polyclonal antibody for detection of p38 from Human, Mouse, Rat. This p38 antibody is for WB, IHC-P, ELISA. It is affinity-purified from rabbit antiserum by affinity-chromatography using epitope-specific immunogenand is unconjugated. The antibody is produced in rabbit by using as an immunogen synthesized peptide derived from human p38 around the non-phosphorylation site of T180/Y182
Description: A polyclonal antibody for detection of p38 from Human, Mouse, Rat. This p38 antibody is for WB, IHC-P, ELISA. It is affinity-purified from rabbit antiserum by affinity-chromatography using epitope-specific immunogenand is unconjugated. The antibody is produced in rabbit by using as an immunogen synthesized peptide derived from human p38 around the non-phosphorylation site of T180/Y182
Description: A polyclonal antibody for detection of p38 from Human, Mouse, Rat. This p38 antibody is for WB, IHC-P, IF, ELISA. It is affinity-purified from rabbit antiserum by affinity-chromatography using epitope-specific immunogenand is unconjugated. The antibody is produced in rabbit by using as an immunogen synthesized peptide derived from human p38 around the non-phosphorylation site of Y323
Description: A polyclonal antibody for detection of p38 from Human, Mouse, Rat. This p38 antibody is for WB, IHC-P, IF, ELISA. It is affinity-purified from rabbit antiserum by affinity-chromatography using epitope-specific immunogenand is unconjugated. The antibody is produced in rabbit by using as an immunogen synthesized peptide derived from human p38 around the non-phosphorylation site of Y323
Description: A polyclonal antibody for detection of p38 from Human, Mouse, Rat. This p38 antibody is for WB, IHC-P, IF, ELISA. It is affinity-purified from rabbit antiserum by affinity-chromatography using epitope-specific immunogenand is unconjugated. The antibody is produced in rabbit by using as an immunogen synthesized peptide derived from human p38 around the non-phosphorylation site of Y323
Description: A polyclonal antibody for detection of p38 from Human, Mouse, Rat, Chicken. This p38 antibody is for WB, ELISA. It is affinity-purified from rabbit antiserum by affinity-chromatography using epitope-specific immunogenand is unconjugated. The antibody is produced in rabbit by using as an immunogen synthesized peptide derived from the C-terminal region of human p38
Description: A polyclonal antibody for detection of p38 from Human, Mouse, Rat, Chicken. This p38 antibody is for WB, ELISA. It is affinity-purified from rabbit antiserum by affinity-chromatography using epitope-specific immunogenand is unconjugated. The antibody is produced in rabbit by using as an immunogen synthesized peptide derived from the C-terminal region of human p38
Description: A polyclonal antibody for detection of p38 from Human, Mouse, Rat, Chicken. This p38 antibody is for WB, ELISA. It is affinity-purified from rabbit antiserum by affinity-chromatography using epitope-specific immunogenand is unconjugated. The antibody is produced in rabbit by using as an immunogen synthesized peptide derived from the C-terminal region of human p38
Uneven geographical distribution and dissemination of MTBC species means that the research findings of individuals from one country or region can not be generalized across the continent. Thus, the generalization of data from previous research studies and ongoing in the MTBC may be inaccurate and inappropriate. A major rethink is needed about the design and structure of future clinical trials of new interventions. West, Central, East and Southern Africa EDCTP Networks of Excellence provides an opportunity to take forward this pan-African studies.