Soluble immunological markers of disease activity in tuberculosis

Abstract

The obtention of a microbiologically confirmed diagnosis of tuberculosis (TB), assessment of the extent and intensity of disease activity, and follow-up of the patient response to treatment are all encumbered by our still limited ability to quantify the infectious load using the microbiological tools available in current practice. In this context, a number of attempts have been made to determine the role that soluble disease markers could play as diagnostic and prognostic indicators in pulmonary, pleural and extrapulmonary TB. As in other lung diseases, molecules which become overexpressed during immune cell activation have been measured in biological fluids such as serum, pleural fluid and the epithelial lining fluid (ELF) of the lower respiratory tract of TB patients, with the intent of gauging the activation of the immune system in response to the TB bacillus, to assess disease activity and predict the disease course.A number of specific and nonspecific immune marker studies have thus appeared in the literature in the last twenty years. Among them Mycobacterium tuberculosis-specific serum antibodies, the T-lymphocyte enzyme adenosine deaminase, the macrophage activation product neopterin, the mononuclear cell surface protein b 2 microglobulin, soluble T-cell interleukin (IL)-2 receptors as well as soluble CD4 and CD8 receptors, macrophage and T-cell adhesion molecules and acute phase reactant proteins have all been proposed as indicators of disease activity in pulmonary and extrapulmonary TB [1±5] and as diagnostic and prognostic indicators in tuberculous pleural effusions [6]. More recently, the cytokines tumour necrosis factor (TNF-a), IL-1, IL-6, interferon gamma (IFN-c) and IL-12 and the chemokines IL-8, monocyte chemotactic peptide-1 (MCP-1) and regulated on activation, normal T cell expressed and secreted (RANTES) have been found to be elevated in the bronchoalveolar lavage fluid or serum of patients with active disease and have been proposed as markers of disease activity [7±12]. However, none of these markers has shown itself as unarguably better than the measurement of haemoglobin concentration and of erythrocyte sedimentation rate, which are the most inexpensive and generally used inflammation markers.By analogy with the other major disease caused by a mycobacterium, leprosy, in which a relationship between the type of immune reaction, the immunopathology and the clinical course has been characterized in the lepromatous and tuberculoid forms of leprosy [13], the identification of immunological markers of the "classic" pathological expressions of disease, i.e. the exudative and productive forms of TB, has been attempted, although not as successfully. Based upon the leprosy model, a spectrum of immunopathological reactions was identified in TB in 1977 [14], whereby the tuberculin reaction and the level of specific antibodies in serum were proposed as the markers of a spectrum of clinical presentations. In that study, the self-limiting course and the good response to chemotherapy of paucibaciliary prod...

Differential Cytokine Secretion and Early Treatment Response in Patients with Pulmonary Tuberculosis

“…The differential expression of IL-6 and IP-10 observed between healthy controls with LTBI and active TB patients before treatment is indicative of disease activity, and is consistent with previous reports on IL-6 [9,[19][20][21] and with the study of Azzuri et al [22]. KL-6 is secreted principally by type II pneumocytes and associated with lung injury and the consistently high levels of KL-6 in active TB patients is in keeping with previous publications on lung diseases [23][24][25].…”

Differential cytokine secretion and early treatment response in patients with pulmonary tuberculosis

“…The differential expression of IL‐6 and IP‐10 observed between healthy controls with LTBI and active TB patients before treatment is indicative of disease activity, and is consistent with previous reports on IL‐6 [9,19–21] and with the study of Azzuri et al. [22].…”

Immune parameters as markers of tuberculosis extent of disease and early prediction of anti-tuberculosis chemotherapy response

“…The function and the potential application of CRP, 26,27 sICAM, 9,14 suPAR, 10 LAG-3, 16 granzyme B 15 and sTNFRs 11,13,28 as single markers of disease activity and progression in M. tuberculosis infection and other diseases are well documented in the literature but these markers do not have a sufficient predictive ability on an individual level. Furthermore, few studies have included combinations of potential markers.…”