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Response to region of difference 1 (RD1) epitopes in human immunodeficiency virus (HIV)-infected individuals enrolled with suspected active tuberculosis: a pilot study

  1. D. Vincenti1,
  2. S. Carrara1,
  3. O. Butera1,
  4. F. Bizzoni1,
  5. R. Casetti2,
  6. E. Girardi3,
  7. D. Goletti1,*

Article first published online: 3 AUG 2007

DOI: 10.1111/j.1365-2249.2007.03462.x

Issue

Clinical & Experimental Immunology

Clinical & Experimental Immunology

Volume 150, Issue 1, pages 91–98, October 2007

Additional Information

How to Cite

Vincenti, D., Carrara, S., Butera, O., Bizzoni, F., Casetti, R., Girardi, E. and Goletti, D. (2007), Response to region of difference 1 (RD1) epitopes in human immunodeficiency virus (HIV)-infected individuals enrolled with suspected active tuberculosis: a pilot study. Clinical & Experimental Immunology, 150: 91–98. doi: 10.1111/j.1365-2249.2007.03462.x

Author Information

  1. 1

    Translational Research Unit,

  2. 2

    Cellular Immunology Unit,

  3. 3

    Clinical Epidemiology Unit, Department of Experimental Research, Istituto Nazionale Malattie Infettive Lazzaro Spallanzani- IRCCS Rome, Italy

*Delia Goletti, Laboratorio di collegamento tra ricerca di base e clinica, ‘Padiglione Del Vecchio’, Istituto Nazionale per le Malattie Infettive ‘Lazzaro Spallanzani’, IRCCS, Roma 00149, Italy. E-mail: d.goletti@tiscali.it

Publication History

  1. Issue published online: 3 AUG 2007
  2. Article first published online: 3 AUG 2007
  3. Accepted for publication 12 June 2007

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Keywords:

  • effector/memory T cells;
  • HIV-TB;
  • IFN-γ;
  • RD1 assays;
  • recall antigen response

Summary

Tuberculosis is the most frequent co-infection in human immunodeficiency virus (HIV)-infected individuals, and which still presents diagnostic difficulties. Recently we set up an assay based on interferon (IFN)-γ response to region of difference 1 (RD1) peptides selected by computational analysis which is associated with active Mycobacterium tuberculosis replication. The objective of this study was to investigate the response to RD1 selected peptides in HIV-1-infected individuals in a clinical setting. The mechanisms of this immune response and comparison with other immune assays were also investigated. A total of 111 HIV-infected individuals with symptoms and signs consistent with active tuberculosis were enrolled prospectively. Interferon (IFN)-γ responses to RD1 selected peptides and recall antigens were evaluated by enzyme-linked immunospot assay. Results were correlated with CD4+ T cell counts, individuals' characteristics, tuberculin skin test, QuantiFERON-TB Gold and T-SPOT.TB. Results from 21 (19%) individuals were indeterminate due to in vitro cell anergy. Among ‘non-anergic’ individuals, sensitivity for active tuberculosis of the assay based on RD1 selected peptides was 67% (24 of 36), specificity was 94% (three of 54). The assay also resulted positive in cases of extra-pulmonary and smear-negative pulmonary active tuberculosis. The response was mediated by CD4+ effector/memory T cells and correlated with CD4+ T cell counts, but not with plasma HIV-RNA load. Moreover, the RD1 selected peptides assay had the highest diagnostic odds ratio for active tuberculosis compared to tuberculin skin test (TST), QuantiFERON-TB Gold and T-SPOT.TB. RD1 selected peptides assay is associated with M. tuberculosis replication in HIV-infected individuals, although T cell anergy remains an important obstacle to be overcome before the test can be proposed as a diagnostic tool.

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