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Clinical features and cause analysis of false positive results of Aspergillus galactomannan assay in pulmonary cryptococcosis patients

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Abstract

There have been conflicting reports of false positive galactomannan assay results in patients with systemic cryptococcosis. We sought to determine the frequency of GM positivity in patients with pulmonary cryptococcosis and confirm the source of this cross-reactivity in vitro. We conducted a retrospective study to elucidate the rate of galactomannan (GM) false positivity and cause in a cohort of 29 patients with pulmonary cryptococcal disease. The production of GM cross-reacting substances by clinical isolates and laboratory isolates of C. neoformans was tested in vitro. The mean serum GM index (Platelia Aspergillus) in patients with pulmonary cryptococcosis was 1.06, with 16 (55.2%) of patients having values above the positive cutoff value of 0.5. GM index values significantly decreased after treatment of cryptococcosis. There was no significant correlation between galactomannan and cryptococcal glucuronoxylomannan antigen (Eiken Latex test) results. Culture supernatants from clinical isolates and wild-type C. neoformans did not react in the GM assay; however, growth in the presence of 6% sodium chloride induced the production of cross-reacting GM antigens in culture supernatants from clinical isolates, wild type and a glucuronoxylomannan-deficient mutant of C. neoformans, but not in culture supernatants from a galactoxylomannan-deficient strain. Our results support the cross-reactivity of cryptococcal galactoxylomannan with the serum GM assay in vitro and in patients with pulmonary cryptococcal infection.

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References

  1. Maertens JA, Klont R, Masson C, Theunissen K, Meersseman W, Lagrou K, Heinen C, Crepin B, Van Eldere J, Tabouret M, Donnelly JP, Verweij PE (2007) Optimization of the cutoff value for the Aspergillus double-sandwich enzyme immunoassay. Clin Infect Dis 44(10):1329–1336

    Article  CAS  PubMed  Google Scholar 

  2. Zandijk E, Mewis A, Magerman K, Cartuyvels R (2008) False-positive results by the platelia Aspergillus galactomannan antigen test for patients treated with amoxicillin-clavulanate. Clin Vaccine Immunol 15(7):1132–1133

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Mennink-Kersten MA, Ruegebrink D, Klont RR, Warris A, Gavini F, Op den Camp HJ, Verweij PE (2005) Bifidobacterial lipoglycan as a new cause for false-positive platelia Aspergillus enzyme-linked immunosorbent assay reactivity. J Clin Microbiol 43(8):3925–3931

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Murashige N, Kami M, Kishi Y, Fujisaki G, Tanosaki R (2005) False-positive results of Aspergillus enzyme-linked immunosorbent assays for a patient with gastrointestinal graft-versus-host disease taking a nutrient containing soybean protein. Clin Infect Dis 40(2):333–334

    Article  PubMed  Google Scholar 

  5. Viscoli C, Machetti M, Cappellano P, Bucci B, Bruzzi P, Van Lint MT, Bacigalupo A (2004) False-positive galactomannan platelia Aspergillus test results for patients receiving piperacillin-tazobactam. Clin Infect Dis 38(6):913–916

    Article  PubMed  Google Scholar 

  6. Vergidis P, Razonable RR, Wheat LJ, Estes L, Caliendo AM, Baden LR, Wingard JR, Baddley J, Assi M, Norris S, Chandrasekar P, Shields R, Nguyen H, Freifeld A, Kohler R, Kleiman M, Walsh TJ, Hage CA (2014) Reduction in false-positive Aspergillus serum galactomannan enzyme immunoassay results associated with use of piperacillin-tazobactam in the United States. J Clin Microbiol 52(6):2199–2201

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Tortorano AM, Esposto MC, Prigitano A, Grancini A, Ossi C, Cavanna C, Cascio GL (2012) Cross-reactivity of Fusarium spp. in the Aspergillus galactomannan enzyme-linked immunosorbent assay. J Clin Microbiol 50(3):1051–1053

    Article  PubMed  PubMed Central  Google Scholar 

  8. Vergidis P, Walker RC, Kaul DR, Kauffman CA, Freifeld AG, Slagle DC, Kressel AB, Wheat LJ (2012) False-positive Aspergillus galactomannan assay in solid organ transplant recipients with histoplasmosis. Transpl Infect Dis 14(2):213–217

    Article  CAS  PubMed  Google Scholar 

  9. Dalle F, Charles PE, Blanc K, Caillot D, Chavanet P, Dromer F, Bonnin A (2005) Cryptococcus neoformans Galactoxylomannan contains an epitope(s) that is cross-reactive with Aspergillus galactomannan. J Clin Microbiol 43(6):2929–2931

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. De Jesus M, Hackett E, Durkin M, Connolly P, Casadevall A, Petraitiene R, Walsh TJ, Wheat LJ (2007) Galactoxylomannan does not exhibit cross-reactivity in the platelia Aspergillus enzyme immunoassay. Clin Vaccine Immunol 14(5):624–627

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. De Pauw B, Walsh TJ, Donnelly JP, Stevens DA, Edwards JE, Calandra T, Pappas PG, Maertens J, Lortholary O, Kauffman CA, Denning DW, Patterson TF, Maschmeyer G, Bille J, Dismukes WE, Herbrecht R, Hope WW, Kibbler CC, Kullberg BJ, Marr KA, Munoz P, Odds FC, Perfect JR, Restrepo A, Ruhnke M, Segal BH, Sobel JD, Sorrell TC, Viscoli C, Wingard JR, Zaoutis T, Bennett JE, European Organization for R, Treatment of Cancer/Invasive Fungal Infections Cooperative G, National Institute of A, Infectious Diseases Mycoses Study Group Consensus G (2008) Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clin Infect Dis 46(12):1813–1821

    Article  PubMed  PubMed Central  Google Scholar 

  12. Zaragoza O, Casadevall A (2004) Experimental modulation of capsule size in Cryptococcus neoformans. Biol Proced Online 6:10–15

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Nelson RT, Hua J, Pryor B, Lodge JK (2001) Identification of virulence mutants of the fungal pathogen Cryptococcus neoformans using signature-tagged mutagenesis. Genetics 157(3):935–947

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Moyrand F, Fontaine T, Janbon G (2007) Systematic capsule gene disruption reveals the central role of galactose metabolism on Cryptococcus neoformans virulence. Mol Microbiol 64(3):771–781

    Article  CAS  PubMed  Google Scholar 

  15. Chen Y, Toffaletti DL, Tenor JL, Litvintseva AP, Fang C, Mitchell TG, McDonald TR, Nielsen K, Boulware DR, Bicanic T, Perfect JR (2014) The Cryptococcus neoformans transcriptome at the site of human meningitis. MBio 5(1):e01087–e01013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Horie M, Tamiya H, Goto Y, Suzuki M, Matsuzaki H, Hasegawa WT, Noguchi S, Kawakami M, Matsuta K, Nagase T, Sakamoto Y (2016) Nonspecific elevation of serum Aspergillus galactomannan antigen levels in patients with rheumatoid arthritis. Respir Investig 54(1):44–49

    Article  PubMed  Google Scholar 

  17. Stynen D, Sarfati J, Goris A, Prevost MC, Lesourd M, Kamphuis H, Darras V, Latge JP (1992) Rat monoclonal antibodies against Aspergillus galactomannan. Infect Immun 60(6):2237–2245

    CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We gratefully acknowledge Dr. Jennifer K. Lodge, Washington University School of Medicine, and Dr. Guilhem Janbon, Pasteur Institute, for providing us with C. neoformans strains.

Funding

DCS was supported by a Foundation award from the Canadian Institutes of Health Research (FDN 159902) and a Research Chair from the Fonds de Recherche Quebec Santé.

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Authors and Affiliations

  1. Department of Infectious Diseases, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan

    Takahiro Takazono, Keitaro Nishimura, Masato Tashiro, Taiga Miyazaki & Koichi Izumikawa

  2. Second Department of Internal Medicine, Nagasaki University Hospital, Nagasaki, Japan

    Takahiro Takazono, Tomomi Saijo, Nobuyuki Ashizawa, Kazuhiro Oshima, Kazuko Yamamoto, Yoshifumi Imamura, Taiga Miyazaki & Hiroshi Mukae

  3. Departments of Medicine, Microbiology and Immunology, McGill University, Montréal, Québec, Canada

    Takahiro Takazono & Donald C. Sheppard

  4. Infectious Diseases and Immunity in Global Health Program, Research Institute of the McGill University Health Centre, Montréal, Québec, Canada

    Takahiro Takazono & Donald C. Sheppard

  5. Department of Laboratory Medicine, Nagasaki University Hospital, Nagasaki, Japan

    Katsunori Yanagihara

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  1. Takahiro Takazono
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  2. Tomomi Saijo
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  13. Donald C. Sheppard
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Corresponding author

Correspondence to Takahiro Takazono.

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The authors declare that they have no conflict of interest.

Ethical approval

The study was approved by the Nagasaki University School of Medicine Research Ethics Committee (Approval no. 16082210).

Informed consent

As this study was a retrospective cohort study, written informed consent was not obtained. However, after approval from the ethics committee of our institute, we have shown the document of “Disclosure of information on clinical research” in our homepage to give the subjects opportunity to declare their will not to participate in this study.

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Takazono, T., Saijo, T., Ashizawa, N. et al. Clinical features and cause analysis of false positive results of Aspergillus galactomannan assay in pulmonary cryptococcosis patients. Eur J Clin Microbiol Infect Dis 38, 735–741 (2019). https://doi.org/10.1007/s10096-019-03469-3

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