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Biomarkers for Early Diagnosis of Hemophagocytic Lymphohistiocytosis in Critically Ill Patients

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Abstract

Many biomarkers have been proposed for the diagnosis of secondary hemophagocytic lymphohistiocytosis (HLH) in adults, but comparative studies are lacking. We analyzed ferritin, glycosylated ferritin, soluble CD25, CD163 and CD14, IL-6, IFN-γ, IL-18, IL-10, IL-1ß, IL-12p70, IL-17α, IP-10, and CXCL9 levels to differentiate HLH from sepsis in critically ill patients. Of 120 patients, HLH was confirmed for 14 patients. Among the biomarkers tested, ferritin, IL-18, and glycosylated ferritin were the most efficient parameters for early diagnosis of HLH. With a sensitivity set at 85%, ferritin, IL-18, and glycosylated ferritin were the biomarkers with the highest specificity: 84, 79, and 71% respectively. Combining IL-18 with the HScore provided a new score with an increased specificity compared to the HScore alone, 86% compared to 70% with a sensitivity set at 100%. A distinct cytokine pattern was highlighted in patients with malignancy-triggered HLH, with highly increased levels of INF-ɣ and CXCL9, compared to HLH secondary to infection. This is the largest study available to date, comparing diagnostic biomarkers for HLH on a cohort of critically ill adult patients. Serum ferritin was the most discriminating parameter for early diagnosis of secondary HLH. IL18*HScore was identified as a highly potential score.

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Funding

This work was supported by a grant from the Brugmann Foundation (grant to FD).

Author information

Authors and Affiliations

  1. Laboratory of Translational Research, Centre Hospitalier Universitaire Brugmann, Université libre de Bruxelles, Brussels, Belgium

    France Debaugnies & Francis Corazza

  2. Medical Biology Department, Laboratoire National de Santé, Dudelange, Luxembourg

    France Debaugnies & Patricia Borde

  3. Microbiology Department, LHUB-ULB, Université libre de Bruxelles, Brussels, Belgium

    Bhavna Mahadeb

  4. Immunology Department, LHUB-ULB, Université libre de Bruxelles, Brussels, Belgium

    Carole Nagant & Francis Corazza

  5. Hematology Department, Jules Bordet Institute, Brussels, Belgium

    Nathalie Meuleman & Adriano Salaroli

  6. Department of Intensive Care, Centre Hospitalier Universitaire Brugmann, Brussels, Belgium

    David De Bels

  7. Clinical Chemistry Department, LHUB-ULB, Université libre de Bruxelles, Brussels, Belgium

    Fleur Wolff

  8. Department of Intensive Care, Hôpitaux IRIS-Sud, Brussels, Belgium

    Philippe Gottignies

  9. Physics of Materials and Optics Unit, University of Mons, Mons, Belgium

    Michel Voué

Authors
  1. France Debaugnies
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  2. Bhavna Mahadeb
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  3. Carole Nagant
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  4. Nathalie Meuleman
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  5. David De Bels
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  6. Fleur Wolff
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  7. Philippe Gottignies
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  8. Adriano Salaroli
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  9. Patricia Borde
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  10. Michel Voué
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  11. Francis Corazza
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Contributions

F.D. and F.C. designed the experiments. F.D., B.M., and C.N. performed the experiments. F.D., M.V., P.B., and F.C. analyzed the data. N.M., D.DB., F.W., P.G., and A.S. recruited the patients and analyzed clinical data. F.D., B.M., and F.C. wrote the manuscript. All authors read, revised, and approved the manuscript.

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Correspondence to France Debaugnies.

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Debaugnies, F., Mahadeb, B., Nagant, C. et al. Biomarkers for Early Diagnosis of Hemophagocytic Lymphohistiocytosis in Critically Ill Patients. J Clin Immunol 41, 658–665 (2021). https://doi.org/10.1007/s10875-020-00950-z

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  • DOI: https://doi.org/10.1007/s10875-020-00950-z

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