IFN-γ signature in the plasma proteome distinguishes pediatric hemophagocytic lymphohistiocytosis from sepsis and SIRS

  • Howard Lin
    Section of Pediatric Hematology-Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, TX;
  • Brooks P. Scull
    Section of Pediatric Hematology-Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, TX;
  • Baruch R. Goldberg
    Children’s Healthcare of Atlanta, Division of Rheumatology, Emory University School of Medicine, Atlanta, GA;
  • Harshal A. Abhyankar
    Section of Pediatric Hematology-Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, TX;
  • Olive E. Eckstein
    Section of Pediatric Hematology-Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, TX;
  • Daniel J. Zinn
    Section of Pediatric Hematology-Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, TX;
  • Joseph Lubega
    Section of Pediatric Hematology-Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, TX;
  • Jennifer Agrusa
    Section of Pediatric Hematology-Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, TX;
  • Nader El Mallawaney
    Section of Pediatric Hematology-Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, TX;
  • Nitya Gulati
    Section of Pediatric Hematology-Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, TX;
  • Lisa Forbes
    Section of Allergy and Immunology;
  • Ivan Chinn
    Section of Allergy and Immunology;
  • Rikhia Chakraborty
    Section of Pediatric Hematology-Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, TX;
  • Jessica Velasquez
    Section of Pediatric Hematology-Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, TX;
  • Jordana Goldman
    Section of Critical Care Medicine, Department of Pediatrics, Texas Children’s Hospital, Houston, TX;
  • Dalia Bashir
    Section of Critical Care Medicine, Department of Pediatrics, Texas Children’s Hospital, Houston, TX;
  • Fong Lam
    Section of Critical Care Medicine, Department of Pediatrics, Texas Children’s Hospital, Houston, TX;
  • Eyal Muscal
    Section of Rheumatology;
  • Michael. M. Henry
    Center for Cancer and Blood Disorders, Phoenix Children's Hospital, Phoenix, AZ;
  • Jay N. Greenberg
    Division of Hematology, Children's National Medical Center, Washington, DC;
  • Stephan Ladisch
    Division of Hematology, Children's National Medical Center, Washington, DC;
  • Michelle L. Hermiston
    Department of Pediatric Hematology/Oncology, University of California, San Francisco, CA;
  • Lauren K. Meyer
    Department of Pediatric Hematology/Oncology, University of California, San Francisco, CA;
  • Michael Jeng
    Department of Pediatrics, Pediatric Hematology/Oncology, Lucile Packard Children's Hospital, Stanford University, Palo Alto, CA;
  • Ahmed Naqvi
    Division of Haematology/Oncology, The Hospital for Sick Children, Toronto, Ontario, Canada;
  • Kenneth McClain
    Section of Pediatric Hematology-Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, TX;
  • Trung Nguyen
    Section of Critical Care Medicine, Department of Pediatrics, Texas Children’s Hospital, Houston, TX;
  • Hector Wong
    Division of Critical Care Medicine; and
  • Tsz-Kwong Man
    Section of Pediatric Hematology-Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, TX;
  • Michael B. Jordan
    Divisions of Immunobiology and Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH
  • Carl E. Allen
    Section of Pediatric Hematology-Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, TX;

抄録

<jats:title>Abstract</jats:title><jats:p>Hemophagocytic lymphohistiocytosis (HLH) is a syndrome characterized by pathologic immune activation in which prompt recognition and initiation of immune suppression is essential for survival. Children with HLH have many overlapping clinical features with critically ill children with sepsis and systemic inflammatory response syndrome (SIRS) in whom alternative therapies are indicated. To determine whether plasma biomarkers could differentiate HLH from other inflammatory conditions and to better define a core inflammatory signature of HLH, concentrations of inflammatory plasma proteins were compared in 40 patients with HLH to 47 pediatric patients with severe sepsis or SIRS. Fifteen of 135 analytes were significantly different in HLH plasma compared with SIRS/sepsis, including increased interferon-γ (IFN-γ)–regulated chemokines CXCL9, CXCL10, and CXCL11. Furthermore, a 2-analyte plasma protein classifier including CXCL9 and interleukin-6 was able to differentiate HLH from SIRS/sepsis. Gene expression in CD8+ T cells and activated monocytes from blood were also enriched for IFN-γ pathway signatures in peripheral blood cells from patients with HLH compared with SIRS/sepsis. This study identifies differential expression of inflammatory proteins as a diagnostic strategy to identify critically ill children with HLH, and comprehensive unbiased analysis of inflammatory plasma proteins and global gene expression demonstrates that IFN-γ signaling is uniquely elevated in HLH. In addition to demonstrating the ability of diagnostic criteria for HLH and sepsis or SIRS to identify groups with distinct inflammatory patterns, results from this study support the potential for prospective evaluation of inflammatory biomarkers to aid in diagnosis of and optimizing therapeutic strategies for children with distinctive hyperinflammatory syndromes.</jats:p>

収録刊行物

  • Blood Advances

    Blood Advances 5 (17), 3457-3467, 2021-08-30

    American Society of Hematology

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