title: Development of immune-biomarkers of pulmonary tuberculosis in a rabbit model.
abstract: Tuberculosis (TB) causes extensive morbidity and mortality worldwide with approximately 10 million new cases of active disease emerging mostly from a pool of two billion individuals latently infected with Mycobacterium tuberculosis (M. tb) every year. The underlying host immune responses that drive M. tb infection to active disease or latency are not well understood. We propose that identification and characterization of host immune biomarkers will be helpful to better understand the mechanisms that drive this process, and may, in addition, lead to the development of better diagnostic tools for TB. We have previously reported the profiles of plasma immune biomarkers in pulmonary TB patients in endemic countries, and in M. tb-infected nonhuman primates. However, biomarker profiling for a cost-effective and user-friendly animal model relevant to human disease, such as rabbit, has not been developed. One challenge in the analysis of circulating cytokines/chemokines for rabbit model of TB is the limited availability of validated immune-reagents. Here we report the use of a commercially available multiplex microbead human cytokine/chemokine panels as development platform for rabbit immune reagents. The results demonstrate their utility to determine circulating analytes and define their profiles related to TB in the rabbit model. In addition, we report the profiles of circulating anti-M. tb antibodies in the plasma of rabbits with active pulmonary TB. These studies show that the pattern of expression of circulating immune biomarkers correlate with TB pathology in rabbits, and are similar to those defined in pulmonary TB patients.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of California, Davis, USA.
authors.forename: Ali
authors.initials: A
authors.lastname: Dehnad
authors.affiliation: Department of Pathology and Laboratory Medicine, University of California, Davis, USA.
authors.forename: Resmi
authors.initials: R
authors.lastname: Ravindran
authors.affiliation: Laboratory of Mycobacterial Immunity and Pathogenesis, Public Health Research Institute (PHRI), New Jersey Medical School, Rutgers Biomedical and Health Sciences, Rutgers, The State University of New Jersey, USA. Electronic address: subbiase@njms.rutgers.edu.
authors.forename: Selvakumar
authors.initials: S
authors.lastname: Subbian
authors.affiliation: Department of Pathology and Laboratory Medicine, University of California, Davis, USA. Electronic address: ihkhan@ucdavis.edu.
authors.forename: Imran H
authors.initials: IH
authors.lastname: Khan
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D007118:Immunoassay / Q000379:methods; D008863:Microspheres; D009169:Mycobacterium tuberculosis / Q000276:immunology; D011817:Rabbits; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis* / Q000276:immunology / Q000382:microbiology
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D015415:Biomarkers; D016207:Cytokines
keywords: Immune biomarker; Multiplex microbead assay; Mycobacterium tuberculosis; Pulmonary active TB; Rabbit