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Diagnosis of occult tuberculosis in hematological malignancy by enumeration of antigen-specific T cells

Leukemia volume 20, pages 379–381 (2006)Cite this article

Hairy cell leukemia is a rare indolent lymphoproliferative malignancy characterized by splenomegaly and pancytopenia. Patients are prone to acquire life-threatening infections and can develop mycobacterial diseases.1 Traditional tools for tuberculosis diagnosis rely on the identification of mycobacteria through microscopy and culture. These methods have low sensitivity and so cannot usefully rule out a diagnosis of tuberculosis where this is suspected. Moreover, mycobacterial culture can take several weeks, often delaying diagnosis and initiation of therapy. As a result, a significant proportion of tuberculosis patients are diagnosed only at autopsy. This diagnostic delay, and its adverse consequences, are even greater in immunosuppressed patients in whom the clinical presentation is frequently nonspecific and the progression of tuberculosis is more rapid.

The tuberculin skin test (TST) confirms infection and not active disease, but in low burden countries (where the prevalence of latent tuberculosis infection in the general population is low), a positive TST result can help in the decision to start treatment while mycobacterial culture results are awaited, or support a clinical diagnosis of tuberculosis when bacteriological confirmation is lacking. Conversely, a negative result might, in theory, help to rule out a diagnosis of tuberculosis. However, the TST is of little help in immunosuppressed patients, such as those with hematological malignancies, who often have falsely negative TST results.2 A test of Mycobacterium tuberculosis infection with high diagnostic sensitivity would therefore be useful in the evaluation of immunosuppressed patients where tuberculosis is included in the differential diagnosis. The ex vivo enzyme-linked immunospot (ELISPOT) assay is a very sensitive method for detecting low frequencies of antigen-specific interferon-γ-producing T cells direct from peripheral blood. Thus, it may provide a more sensitive means of detecting M. tuberculosis-specific immune responses than the TST, which measures cutaneous delayed-type hypersensitivity to purified protein derivative (PPD). Two M. tuberculosis gene products, early secretory antigen target-6 (ESAT-6) and culture filtrate protein-10 (CFP-10), are strong targets of cellular immune response in tuberculosis patients and contacts.3 Recently, the ELISPOT-RD1 assay for interferon-γ-producing T-cells specific for ESAT-6 or CFP-10 peptides, has been demonstrated to be a rapid, highly sensitive and specific diagnostic tool for the detection of M. tuberculosis infection, including in immunosuppressed individuals.4, 5, 6 Here, we describe how the ELISPOT-RD1 accelerated the diagnosis of disseminated tuberculosis in a leukemic patient with persistent fever and a negative TST.

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Acknowledgements

This work was supported by the Wellcome Trust (UK) and Azienda Ospedaliera Policlinico di Modena (Italy). We thank Roslyn Kemp, Tim Hinks, Oni Chowdhury and Sarah Gooding for their helpful comments.

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Authors and Affiliations

  1. Respiratory Disease, University of Modena and Reggio Emilia, Modena, Italy

    L Richeldi, M Losi, F Luppi, P Roversi, S Cerri & L M Fabbri

  2. Hematology Clinic, University of Modena and Reggio Emilia, Modena, Italy

    M Luppi, L Potenza & G Torelli

  3. Nuffield Department of Clinical Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK

    K A Millington, K Ewer & A Lalvani

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  1. L Richeldi
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Correspondence to A Lalvani.

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Richeldi, L., Luppi, M., Losi, M. et al. Diagnosis of occult tuberculosis in hematological malignancy by enumeration of antigen-specific T cells. Leukemia 20, 379–381 (2006). https://doi.org/10.1038/sj.leu.2404053

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