IFN-γ, but not IP-10, MCP-2 or IL-2 response to RD1 selected peptides associates to active tuberculosis

Accepted 5 May 2010. published online 18 June 2010.

Summary

Objectives

To evaluate whether in vitro response to Mycobacterium tuberculosis RD1 peptides selected by computational analysis, measured by IFN-γ, IP-10, MCP-2 or IL-2 production, is associated with active tuberculosis (TB) in a country with a high incidence of TB.

Methods

129 individuals were prospectively enrolled, 41 with active-pulmonary TB and 88 without (household contacts and community controls). A whole blood assay based on RD1 selected peptides was performed. Soluble factors were evaluated by ELISA in plasma harvested at day1-post-culture. Enrolled individuals were also tested by QuantiFERON TB-Gold In tube (QFT-IT) and tuberculin skin tests (TST).

Results

IFN-γ response to RD1 selected peptides was significantly higher in active TB patients than in household contacts and community controls. IP-10 and MCP-2 response did not differ between active TB patients and household contacts, although it was higher in these groups compared to community controls; conversely IL-2 response did not differ among the three groups. When IFN-γ response to RD1 selected peptides was scored based on receiver-operator-characteristic analysis, active TB was predicted with 68% sensitivity and 86% specificity. QFT-IT and TST showed a sensitivity for active TB of 90% and 68% and a specificity of 58% and 59%, respectively.

Conclusions

IFN-γ (but not IP-10, MCP-2 and IL-2) response to RD1 selected peptides is associated with active TB with a higher specificity than QFT-IT and TST.

Keywords: Tuberculosis, LTBI, IGRA, RD1 peptides, IP-10, MCP-2, IL-2

a Translational Research Unit, Department of Epidemiology and Preclinical Research, L. Spallanzani National Institute for Infectious Diseases (INMI), Via Portuense 292, Rome, Italy

b Department of Immunology, Tuberculosis Research Centre (ICMR), Tamil Nadu, India

c Microbiology Department, P.D. Hinduja National Hospital and Research Center, Mumbai, India

d Scientific Direction, Fondation Mérieux, Lyon, France

e Scientific Direction, INMI, Rome, Italy

f BioMérieux, Research & Development Immunoasays, Chemin del’Orme, Marcy L’Etoile, France

g Department of Epidemiology and Preclinical Research, INMI, Rome, Italy

h Microbiology Service, Saint Louis Hospital, Paris, France

Corresponding author. Tel.: +39 06 55170 906 (954); fax: +39 06 5582 825.

PII: S0163-4453(10)00133-7

doi:10.1016/j.jinf.2010.05.002

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