Introduction In screening for tuberculosis (TB), we need to distinguish between active and latent TB. In those with a positive interferon-gamma release assay (IGRA) additional tests are required to identify active TB. Proteomic fingerprinting suggested that four proteins (C-reactive protein (CRP), transthyretin, neopterin, and serum amyloid A (SAA)) might be able to distinguish active from latent disease.¹

Methods Patients were grouped to reflect different stages of infection and those with latent TB were followed for over eight years. These groups were: 1) Smear-positive TB (n = 20), 2) Smear-negative/culture-positive TB (n = 12), 3) Recent TB contacts with positive interferon-gamma release assay (IGRA) (n = 15), and 4) No TB detected with firm alternative diagnosis (n = 12). All patients in groups 1 to 3 and 25% of group 4 were IGRA positive. Serum samples were collected and enzyme-linked immunosorbent assays (ELISAs) were performed to measure C-reactive protein, transthyretin, neopterin, and serum amyloid A found in the serum samples from each group. Standard cut-off values were used for each protein and results labelled as either positive or negative. Chi-square calculations were used to determine the significance of the results in differentiating between active TB, latent TB, and absence of TB infection.

Results All four biomarkers were positive in smear-positive TB, but SAA and CRP were less sensitive in smear-negative TB (see attached table). Even in the control group, there were positive tests for the four biomarkers. None of those with latent TB developed active disease, even though a proportion had a positive test.

Conclusion These four biomarkers did not distinguish between active and latent disease, and did not predict the development of active disease in those with latent TB infection.

Reference

1. Agranoff D, Fernandez-Reyes D, Papadopoulos MC, Rojas SA, Herbster M, Loosemore A, Tarelli E, Sheldon J, Schwenk A, Pollok, Rayner CF, Krishna S. Indentification of diagnostic markers for tuberculosis by proteomic fingerprinting of serum. Lancet 2006;368:1012–21