Publication Date
4-29-2021
Journal
Blood
DOI
10.1182/blood.2020009499
PMID
33512385
PMCID
PMC8085480
PubMedCentral® Posted Date
12-10-2020
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
ADP-ribosyl Cyclase 1, Adolescent, Adult, CD8-Positive T-Lymphocytes, Case-Control Studies, Child, Child, Preschool, Cytokine Release Syndrome, Diagnosis, Differential, Female, HLA-DR Antigens, Humans, Infant, Lymphocyte Activation, Lymphohistiocytosis, Hemophagocytic, Male, Membrane Glycoproteins, Sepsis, Young Adult
Abstract
Hemophagocytic lymphohistiocytosis (HLH) is a fatal disorder of immune hyperactivation that has been described as a cytokine storm. Sepsis due to known or suspected infection has also been viewed as a cytokine storm. Although clinical similarities between these syndromes suggest similar immunopathology and may create diagnostic uncertainty, distinguishing them is critical as treatments are widely divergent. We examined T-cell profiles from children with either HLH or sepsis and found that HLH is characterized by acute T-cell activation, in clear contrast to sepsis. Activated T cells in patients with HLH were characterized as CD38high/HLA-DR+ effector cells, with activation of CD8+ T cells being most pronounced. Activated T cells were type 1 polarized, proliferative, and displayed evidence of recent and persistent activation. Circulating activated T cells appeared to be broadly characteristic of HLH, as they were seen in children with and without genetic lesions or identifiable infections and resolved with conventional treatment of HLH. Furthermore, we observed even greater activation and type 1 polarization in tissue-infiltrating T cells, described here for the first time in a series of patients with HLH. Finally, we observed that a threshold of >7% CD38high/HLA-DR+ cells among CD8+ T cells had strong positive and negative predictive value for distinguishing HLH from early sepsis or healthy controls. We conclude that the cytokine storm of HLH is marked by distinctive T-cell activation whereas early sepsis is not, and that these 2 syndromes can be readily distinguished by T-cell phenotypes.
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