title: Development of a T7 Phage Display Library to Detect Sarcoidosis and Tuberculosis by a Panel of Novel Antigens.
abstract: Sarcoidosis is a granulomatous inflammatory disease, diagnosed through tissue biopsy of involved organs in the absence of other causes such as tuberculosis (TB). No specific serologic test is available to diagnose and differentiate sarcoidosis from TB. Using a high throughput method, we developed a T7 phage display cDNA library derived from mRNA isolated from bronchoalveolar lavage (BAL) cells and leukocytes of sarcoidosis patients. This complex cDNA library was biopanned to obtain 1152 potential sarcoidosis antigens and a microarray was constructed to immunoscreen two different sets of sera from healthy controls and sarcoidosis. Meta-analysis identified 259 discriminating sarcoidosis antigens, and multivariate analysis identified 32 antigens with a sensitivity of 89% and a specificity of 83% to classify sarcoidosis from healthy controls. Additionally, interrogating the same microarray platform with sera from subjects with TB, we identified 50 clones that distinguish between TB, sarcoidosis and healthy controls. The top 10 sarcoidosis and TB specific clones were sequenced and homologies were searched in the public database revealing unique epitopes and mimotopes in each group. Here, we show for the first time that immunoscreenings of a library derived from sarcoidosis tissue differentiates between sarcoidosis and tuberculosis antigens. These novel biomarkers can improve diagnosis of sarcoidosis and TB, and may aid to develop or evaluate a TB vaccine.
authors.affiliation: Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, Wayne State University School of Medicine and Detroit Medical Center, Detroit, MI 48201.
authors.forename: Harvinder
authors.initials: H
authors.lastname: Talwar
authors.affiliation: Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, Wayne State University School of Medicine and Detroit Medical Center, Detroit, MI 48201.
authors.forename: Rita
authors.initials: R
authors.lastname: Rosati
authors.affiliation: Department of Public Health Sciences, Henry Ford Health System, Detroit, MI 48202.
authors.forename: Jia
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, Wayne State University School of Medicine and Detroit Medical Center, Detroit, MI 48201.
authors.forename: Dana
authors.initials: D
authors.lastname: Kissner
authors.affiliation: Department of Family Medicine and Public Health Sciences, Wayne State University School of Medicine, 3939 Woodward, 220, Detroit, MI 48201.
authors.forename: Samiran
authors.initials: S
authors.lastname: Ghosh
authors.affiliation: Division of Rheumatology, Wayne State University School of Medicine and Detroit Medical Center, Detroit, MI 48201.
authors.forename: Félix Fernández
authors.initials: FF
authors.lastname: -Madrid
authors.affiliation: Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, Wayne State University School of Medicine and Detroit Medical Center, Detroit, MI 48201 ; Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, 540 E. Canfield, Detroit, MI 48201, USA.
authors.forename: Lobelia
authors.initials: L
authors.lastname: Samavati
keywords: IgG; Immunoscreening; Microarray; Sarcoidosis; T7phage library; Tuberculosis