A recent publication in Lancet Infectious Diseases (Broger et al., 2019) describe an innovative assay that can diagnose Tuberculosis infection by detecting the presence of the Tuberculosis biomarker, lipoarabinomannan (LAM) in the urine of patients with considerably greater sensitivity than previously possible. The assay, called Fujifilm SILVAMP TB LAM, was developed in a collaboration between Dr. Abraham Pinter’s laboratory at Rutgers, and an international team, that included scientists at the Foundation for Innovative New Diagnostics (FIND) in Geneva and Fujifilm. A key component of the assay was a novel human monoclonal antibody isolated by Dr. Alok Choudhary, a member of Dr. Pinter’s team, from the blood of a patient at the Rutgers Global Tuberculosis Institute who was infected with TB. This antibody, when paired with a second capture antibody isolated at Otsuka Pharmaceutical, has a unique ability to detect the form of the LAM antigen present in the urine of patients.
The properties of these antibodies that are responsible for the unique sensitivity and specificity of this assay were originally described in papers from the Pinter lab and collaborators published last year (Choudhary et al., 2018, Amin et al., 2018, Sigal et al., 2018). The Pinter laboratory is currently working on methods to enhance the properties of these antibodies and further improve the sensitivity of the assay. The goal of these studies is to develop an inexpensive assay that is highly sensitive and specific for the presence of TB LAM in the urine of patients, that can serve as a widely used point-of-care assay for the early detection of TB infection.
Broger T, Sossen B, du Toit E, Kerkhoff AD, Schutz C, Ivanova Reipold E, Ward A, Barr DA, Mace A, Trollip A, Burton R, Ongarello S, Pinter A, Lowary TL, Boehme C, Nicol MP, Meintjes G, Denkinger CM (2019) Novel lipoarabinomannan point-of-care tuberculosis test for people with HIV: a diagnostic accuracy study. Lancet Infect Dis 19: 852-861. PMI: 31155318
Choudhary A, Patel D, Honnen W, Lai Z, Prattipati RS, Zheng RB, Hsueh YC, Gennaro ML, Lardizabal A, Restrepo BI, Garcia-Viveros M, Joe M, Bai Y, Shen K, Sahloul K, Spencer JS, Chatterjee D, Broger T, Lowary TL, Pinter A (2018) Characterization of the Antigenic Heterogeneity of Lipoarabinomannan, the Major Surface Glycolipid of Mycobacterium tuberculosis, and Complexity of Antibody Specificities toward This Antigen. J Immunol 200: 3053-3066. PMI: 29610143
Amin AG, De P, Spencer JS, Brennan PJ, Daum J, Andre BG, Joe M, Bai Y, Laurentius L, Porter MD, Honnen WJ, Choudhary A, Lowary TL, Pinter A, Chatterjee D (2018) Detection of lipoarabinomannan in urine and serum of HIV-positive and HIV-negative TB suspects using an improved capture-enzyme linked immuno absorbent assay and gas chromatography/mass spectrometry. Tuberculosis (Edinb) 111: 178-187. PMI: 30029905
Sigal GB, Pinter A, Lowary TL, Kawasaki M, Li A, Mathew A, Tsionsky M, Zheng RB, Plisova T, Shen K, Katsuragi K, Choudhary A, Honnen WJ, Nahid P, Denkinger CM, Broger T (2018) A Novel Sensitive Immunoassay Targeting the 5-Methylthio-d-Xylofuranose-Lipoarabinomannan Epitope Meets the WHO’s Performance Target for Tuberculosis Diagnosis. J Clin Microbiol 56. PMI: 30257899