DiagnosticsCXCL12 as a biological marker for the diagnosis of tuberculous pleurisy
Introduction
Tuberculosis is histologically characterized by caseating granulomas that consist of predominant aggregation of macrophages and T lymphocytes.1 Macrophages further develop into multinucleated giant epithelioid cells. Lymphocytes, especially T helper 1 (Th1) cells, have to be recruited and accumulated to the inflammation foci from the systemic bloodstream as the first process to develop anti-tuberculosis immunity, however, the mechanism is not well understood.2
Chemokines are small cytokine-like peptides that direct various subsets of hematopoietic cells to specific anatomical sites by ligation with their cognate G-protein coupled receptors.3, 4 CXCL12, also known as stromal cell-derived factor-1α (SDF-1α), is a CXC chemokine that exhibits a variety of biological effects through its only known receptor CXCR4.5, 6, 7 CXCL12 not only has chemotactic activity for broad range of hematopoietic cell linage such as early B cell progenitors, B/T cell subpopulations, monocytes, megakaryocytes and CD34-positive stem cells,8, 9, 10, 11 but also plays critical roles in the development of neural cells, cerebellum, cardiac septum and mesenteric vasculature.12, 13, 14, 15 Moreover, CXCL12/CXCR4 axis has been recently shown to be important in migration and metastasis of solid tumors including lung cancer16 and associated with infectious diseases such as human immunodeficiency virus (HIV) infection6, 7, 17 and viral hepatitis.18
Tuberculous (TB) pleurisy is a frequent clinical manifestation of TB infection in the thorax. Adenosine deaminase (ADA) activity in pleural fluid is a well known useful diagnostic marker for TB effusion. Interferon (IFN)-γ level in pleural fluid is also proven to increase in TB pleurisy with a potentially equal or better diagnostic sensitivity and specificity compared with ADA.19, 20, 21, 22, 23, 24 Since the Th1 lymphocyte is known to play a central role in anti-tuberculosis immune response and CXCL12 is one of the most efficacious T lymphocyte chemoattractants,7 CXCL12 produced from inflammation foci probably triggers mobilization and accumulation of T lymphocytes into the intra-pleural space. However, the clinical significance of CXCL12 in TB pleurisy has never been elucidated thus far. Therefore, we measured CXCL12 concentration in serum and pleural fluid in patients with pleural effusion and evaluated the significance as diagnostic marker for TB pleurisy. We also compared CXCL12 with IFN-γ and ADA in terms of their diagnostic power to differentiate TB pleurisy from non-TB.
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Patients and diagnosis criteria for pleurisy
The study protocol had been approved by the institutional ethical committee at National Hospital Organization Toneyama National Hospital (Osaka, Japan). Sixty patients with pleural effusion from any cause who had given written informed consent were enrolled in this study from 2003 to 2007. Their pleural effusions and sera were collected and stored at −80 °C until measurement. Five healthy volunteers also provided their sera as controls. Patients were classified into two subgroups according to
Patient profile with pleural effusion
The study group consisted of 38 men and 22 women. TB etiology was confirmed in 10 (16.7%) as “definite” and 5 (8.3%) as “clinical”, respectively. The rest of the 45 non-TB patients were with effusion secondary to lung carcinoma (50.0%) (n = 30; 23 non-small cell and 7 small cell histology), empyema (11.7%) (n = 7) and miscellaneous (13.3%) (n = 8; 3 cardiac failure, 2 rheumatoid arthritis, 3 idiopathic). The median age was 52 (ranging 21–80) in TB patients and 71 (ranging 33–86) in non-TB
Discussion
TB pleurisy generally affects younger people in countries with higher incidence of TB infection, whereas TB patients are getting older in industrial countries. The reason is presumed that majority is caused by reactivation in the latter countries while caused by primary infection in the former countries. Japan is still in the middle of both regarding TB incidence.27, 28 In our present study, 7 patients are of 20–30’s, who are considered to be infected primarily, and possibly account for the
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Platelets immune response against Mycobacterium tuberculosis infection
2021, Microbial PathogenesisCitation Excerpt :Our results contrast with previous studies that consider platelets as the first recruited cells into the sites of infection [8], but is in agreement with the presence of platelets during late disease, when extensive inflammation and tissue damage is produced by the strong immune response against Mtb [17]. It has been reported that during Mtb infection there is an increment in CXCL12 expression [22], and the receptors for this chemokine (CXCR4 and CXCR7) are expressed by platelets [23,24]. Thus, the platelets recruitment observed during late experimental TB could be induced through these receptors; although it cannot be discarded that other chemokines could participate, since several chemokine receptors have been found in platelets.
Serum levels of chemokines IP-10, IL-8 and SDF-1 serve as good biomarkers for diabetes-tuberculosis nexus
2018, Journal of Diabetes and its ComplicationsCitation Excerpt :SDF-1 levels were significantly increased in TB+ subjects compared to healthy controls. Previously Khomo et al., reported significantly increased levels of SDF-1 in the pleural fluid of TB patients.18 However, with respect to diabetes, no significant change was seen with respect to SDF-1 levels in DM groups compared to NGT.
Expression profile of CXCL12 chemokine during M. tuberculosis infection with different therapeutic interventions in guinea pig
2018, Indian Journal of TuberculosisCitation Excerpt :In addition, IFN-γ and other cytokines and chemokines that have been documented as bio-markers for diagnosis of MTB infection. For example, IL-10, IL-6, IL-4, CXCL12, CXCL10, CXCL8, and CCL8 levels are possibly associated with tuberculosis.14,15 CXCL10, CXCL11 and other chemokines of CXC family are actively involved in accelerating the immune responses with vaccines like BCG, MIP and other vaccine candidates, and the levels of chemokines reduced with chemotherapy.16–18
Expression of CXCL10 (IP-10) and CXCL11 (I-TAC) chemokines during Mycobacterium tuberculosis infection and immunoprophylaxis with Mycobacterium indicus pranii (Mw) in guinea pig
2013, Infection, Genetics and EvolutionCitation Excerpt :To emphasize, prior immunization with Mw was found more effective with chemotherapy to control and/or clearance of disease. The release of chemokines belonging to CXC family at the site of infection has been considered as a diagnostic marker (Kohmo et al., 2012) and plays an important role in host defense through recruitment of activated T cells (Sauty et al., 1999). In our present study also, we have found that prior immunoprophylaxis and subsequent chemotherapy was more effective in inhibiting the growth of MTB.
Diagnostic and prognostic value of CXCL12 (SDF-1α) level in Mycobacterium tuberculosis infection and disease
2021, Journal of Infection in Developing Countries
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S. Kohmo and T. Kijima contributed equally to this work.