title: Mucorales-Specific T Cells in Patients with Hematologic Malignancies.
abstract: BACKGROUND
  Invasive mucormycosis (IM) is an emerging life-threatening fungal infection. It is difficult to obtain a definite diagnosis and to initiate timely intervention. Mucorales-specific T cells occur during the course of IM and are involved in the clearance of the infection. We have evaluated the feasibility of detecting Mucorales-specific T cells in hematological patients at risk for IM, and have correlated the detection of such cells with the clinical conditions of the patients.
  
  
  RESULTS
  By using an enzyme linked immunospot assay, the presence of Mucorales-specific T cells in peripheral blood (PB) samples has been investigated at three time points during high-dose chemotherapy for hematologic malignancies. Mucorales-specific T cells producing interferon-γ, interleukin-10 and interleukin-4 were analysed in order to detect a correlation between the immune response and the clinical picture. Twenty-one (10.3%) of 204 patients, accounting for 32 (5.3%) of 598 PB samples, tested positive for Mucorales-specific T cells. Two groups could be identified. Group 1, including 15 patients without signs or symptoms of invasive fungal diseases (IFD), showed a predominance of Mucorales-specific T cells producing interferon-gamma. Group 2 included 6 patients with a clinical picture consistent with invasive fungal disease (IFD): 2 cases of proven IM and 4 cases of possible IFD. The proven patients had significantly higher number of Mucorales-specific T cells producing interleukin-10 and interleukin-4 and higher rates of positive samples by using derived diagnostic cut-offs when compared with the 15 patients without IFD.
  
  
  CONCLUSIONS
  Mucorales-specific T cells can be detected and monitored in patients with hematologic malignancies at risk for IM. Mucorales-specific T cells polarized to the production of T helper type 2 cytokines are associated with proven IM and may be evaluated as a surrogate diagnostic marker for IM.
authors.affiliation: Section of Hematology, Department of Surgical and Medical Sciences, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria Policlinico, Modena, Italy.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Potenza
authors.affiliation: Section of Hematology, Department of Surgical and Medical Sciences, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria Policlinico, Modena, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Vallerini
authors.affiliation: Section of Hematology, Department of Surgical and Medical Sciences, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria Policlinico, Modena, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Barozzi
authors.affiliation: Section of Hematology, Department of Surgical and Medical Sciences, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria Policlinico, Modena, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Riva
authors.affiliation: Section of Hematology, Department of Surgical and Medical Sciences, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria Policlinico, Modena, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Gilioli
authors.affiliation: Section of Hematology, Department of Surgical and Medical Sciences, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria Policlinico, Modena, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Forghieri
authors.affiliation: Hematology and Bone Marrow Transplantation, Azienda Ospedaliero-Universitaria Santa Maria della Misericordia di Udine, Udine, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Candoni
authors.affiliation: Pediatric Hematology/Oncology, Policlinico GB Rossi, Verona, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Cesaro
authors.affiliation: Section of Hematology, Department of Surgical and Medical Sciences, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria Policlinico, Modena, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Quadrelli
authors.affiliation: Department of Hematology, Universitaire Ziekenhuizen Leuven, Campus Gasthuisberg, Leuven, Belgium.
authors.forename: Johan
authors.initials: J
authors.lastname: Maertens
authors.affiliation: Department of Pathology, Azienda Ospedaliero-Universitaria Policlinico, Modena, Italy.
authors.forename: Giulio
authors.initials: G
authors.lastname: Rossi
authors.affiliation: Section of Hematology, Department of Surgical and Medical Sciences, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria Policlinico, Modena, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Morselli
authors.affiliation: Clinic of Infectious Diseases, Integrated Department of Medicine, Emergency Medicine and Medical Specialties, Azienda Ospedaliero-Universitaria Policlinico, Modena, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Codeluppi
authors.affiliation: Clinic of Infectious Diseases, Integrated Department of Medicine, Emergency Medicine and Medical Specialties, Azienda Ospedaliero-Universitaria Policlinico, Modena, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Mussini
authors.affiliation: Section of Hematology, Department of Surgical and Medical Sciences, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria Policlinico, Modena, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Colaci
authors.affiliation: Section of Hematology, Department of Surgical and Medical Sciences, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria Policlinico, Modena, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Messerotti
authors.affiliation: Section of Hematology, Department of Surgical and Medical Sciences, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria Policlinico, Modena, Italy.
authors.forename: Ambra
authors.initials: A
authors.lastname: Paolini
authors.affiliation: Section of Hematology, Department of Surgical and Medical Sciences, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria Policlinico, Modena, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Maccaferri
authors.affiliation: Section of Hematology, Department of Surgical and Medical Sciences, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria Policlinico, Modena, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Fantuzzi
authors.affiliation: Section of Statistics, Department of Diagnostic, Clinical and Public Health Medicine, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria Policlinico, Modena, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Del Giovane
authors.affiliation: Division of Thoracic Surgery, Department of Surgical and Medical Sciences, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria Policlinico, Modena, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Stefani
authors.affiliation: Division of Thoracic Surgery, Department of Surgical and Medical Sciences, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria Policlinico, Modena, Italy.
authors.forename: Uliano
authors.initials: U
authors.lastname: Morandi
authors.affiliation: Section of Hematology, Department of Surgical and Medical Sciences, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria Policlinico, Modena, Italy.
authors.forename: Rossana
authors.initials: R
authors.lastname: Maffei
authors.affiliation: Section of Hematology, Department of Surgical and Medical Sciences, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria Policlinico, Modena, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Marasca
authors.affiliation: Section of Hematology, Department of Surgical and Medical Sciences, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria Policlinico, Modena, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Narni
authors.affiliation: Hematology and Bone Marrow Transplantation, Azienda Ospedaliero-Universitaria Santa Maria della Misericordia di Udine, Udine, Italy.
authors.forename: Renato
authors.initials: R
authors.lastname: Fanin
authors.affiliation: Pediatric Hematology/Oncology and Transplantation, IRCCS Policlinico S. Matteo, Pavia, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Comoli
authors.affiliation: Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy.
authors.forename: Luigina
authors.initials: L
authors.lastname: Romani
authors.affiliation: Unitè des Aspergillus, Pasteur Institut, Paris, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Beauvais
authors.affiliation: Clinic of Infectious Diseases, Department of Internal Medicine, Geriatrics and Nephrologic Diseases, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
authors.forename: Pier Luigi
authors.initials: PL
authors.lastname: Viale
authors.affiliation: Unitè des Aspergillus, Pasteur Institut, Paris, France.
authors.forename: Jean Paul
authors.initials: JP
authors.lastname: Latgè
authors.affiliation: Clinic of Infectious Diseases, Department of Internal Medicine, Geriatrics and Nephrologic Diseases, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
authors.forename: Russell E
authors.initials: RE
authors.lastname: Lewis
authors.affiliation: Section of Hematology, Department of Surgical and Medical Sciences, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria Policlinico, Modena, Italy.
authors.forename: Mario
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authors.lastname: Luppi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D016867:Immunocompromised Host; D015470:Leukemia, Myeloid, Acute / Q000276:immunology* / Q000382:microbiology; D008297:Male; D008875:Middle Aged; D009090:Mucorales / Q000276:immunology*; D009091:Mucormycosis / Q000000981:diagnostic imaging / Q000276:immunology* / Q000382:microbiology; D011859:Radiography; D018418:Th2 Cells / Q000276:immunology* / Q000382:microbiology; D055815:Young Adult