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Diagnosis of invasive aspergillosis by tracking Aspergillus-specific T cells in hematologic patients with pulmonary infiltrates

Leukemia volume 21, pages 578–581 (2007)Cite this article

Invasive aspergillosis (IA) is a leading cause of infection-related mortality in hematologic patients, with death rate ranging from 50 to 90%.1 The reason for this extremely poor outcome is because of the difficulties in a timely and undoubted diagnosis, which still relies on a very high degree of suspicion. The current diagnostic tools are limited by invasiveness, slowness, relative insensitiveness, lack of standardization and unpredictable kinetics.2 The most widely studied test, Galctomannan antigenemia (GM), has been demonstrated to be highly variable in performance, with sensitivity ranging between 29 and 100%, and is affected by several factors related either to the fungus or to the host.2 Furthermore, the detection of Aspergillus DNA through polymerase chain reaction (PCR) is still hampered by the difficulties in understanding the fungal DNA release and kinetics other than by technical barriers.2 For all these reasons, establishing an early diagnosis of IA remains a challenge.1, 2

Recent studies have shown that adaptive immunity contributes to the host defense against Aspergillus species.3 In the murine model of IA, mice resistant to the infection produce a high pulmonary level of T helper1 (TH1) cytokines, whereas mice with a high level of T helper2 (TH2) cytokines suffer from disease progression.4 In a human clinical setting, a study has measured the production of either interferon-γ (IFN-γ) or interleukin-10 (IL-10) in culture supernatants of peripheral blood mononuclear cells (PBMCs) stimulated with Aspergillus antigens, showing that patients with high IFN-γ/IL-10 ratio survive IA.5 Moreover, the adoptive transfer of Aspergillus-specific IFN-γ-producing T-cells (IFN-γ-TH1) has been reported to cure IA in allogeneic bone marrow transplant (alloBMT) patients.6

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Acknowledgements

We are indebted to Professor F Narni, Dr A Donelli, Dr G Riva, Dr A Imovilli and Dr E Rivolti, and the nurse staff of the Department of Oncology and Hematology for the clinical management of the patients, and Professor L Richeldi of the Respiratory Disease Unit for helpful discussion. We are also indebted to Merck Sharp & Dohme and Dr Patrizia Marchegiano and the staff of the Medical Direction of the Azienda Ospedaliera Policlinico of Modena for the fellowship support to one of the authors (FV). Drs Potenza, Barozzi, Torelli and Luppi have applied for an Italian patent regarding clinical applications of the ELISPOT assay for the diagnosis of Aspergillus infection.

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Author notes

  1. L Potenza and P Barozzi: These authors contributed equally to this study

Authors and Affiliations

  1. Department of Oncology and Hematology, Section of Hematology, University of Modena and Reggio Emilia, Azienda Ospedaliera Policlinico, Modena, Italy

    L Potenza, P Barozzi, D Vallerini, R Bosco, C Quadrelli, L Mediani, M Morselli, F Forghieri, F Volzone, G Torelli & M Luppi

  2. Infectious Disease Clinics, University of Modena and Reggio Emilia, Azienda Ospedaliera Policlinico, Modena, Italy

    M Codeluppi

  3. Department of Pathology, University of Modena and Reggio Emilia, Azienda Ospedaliera Policlinico, Modena, Italy

    G Rossi

  4. Department of Surgery, University of Modena and Reggio Emilia, Azienda Ospedaliera Policlinico, Modena, Italy

    G Tazzioli

  5. Microbiology and Virology Unit, University of Modena and Reggio Emilia, Azienda Ospedaliera Policlinico, Modena, Italy

    C Venturelli

Authors
  1. L Potenza
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  14. G Torelli
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  15. M Luppi
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Corresponding author

Correspondence to M Luppi.

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Potenza, L., Barozzi, P., Vallerini, D. et al. Diagnosis of invasive aspergillosis by tracking Aspergillus-specific T cells in hematologic patients with pulmonary infiltrates. Leukemia 21, 578–581 (2007). https://doi.org/10.1038/sj.leu.2404504

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