Ann Lab Med.  2019 Sep;39(5):430-437. 10.3343/alm.2019.39.5.430.

Flow Cytometric Analysis of T Cells in Hemophagocytic Lymphohistiocytosis

• Park MS
• Yoo IY
• Kim HJ
• Kim SH
• Kim SJ
• Cho D

• KMID: 2450965
• DOI: http://doi.org/10.3343/alm.2019.39.5.430

Abstract

BACKGROUND
T cell immunophenotypes in patients with hemophagocytic lymphohistiocytosis (HLH) have been described. Downregulation of CD5 or CD7 on T cells has been reported in patients with Epstein-Barr virus (EBV)-positive HLH. As the utility of T cell immunophenotypes as an adjunctive diagnostic or a prognostic marker for HLH has not been evaluated, we analyzed T cell immunophenotypes in HLH patients for this purpose.
METHODS
We classified 45 HLH patients into three subgroups: EBV-positive HLH (N=27), EBV-negative secondary HLH (N=15), and familial HLH (N=3). We retrospectively characterized downregulation patterns of CD5 or CD7 on activated T cells, using flow cytometry. Overall survival was estimated using Kaplan-Meier curves and compared using the log-rank test.
RESULTS
An aberrant immunophenotype, including CD5 and/or CD7 downregulation on T cells, was observed in 55.6% (15/27) of the EBV-positive HLH patients and 100% of the familial HLH (3/3). Only one (1/15, 6.7%) patient with EBV-negative secondary HLH showed an aberrant loss of CD7 antigen on CD8+ T cells. The presence of an aberrant T cell immunophenotype was not related to overall survival in EBV-positive HLH and EBV-negative secondary HLH patients.
CONCLUSIONS
An aberrant T cell immunophenotype may assist in discriminating EBV-negative secondary HLH and EBV-positive HLH. However, it may not be useful as a prognostic marker.

Keyword

Epstein-Barr virus; Familial; Hemophagocytic lymphohistiocytosis; Flow cytometry; T cell; Overall survival

MeSH Terms

Antigens, CD7
Down-Regulation
Flow Cytometry
Herpesvirus 4, Human
Humans
Lymphohistiocytosis, Hemophagocytic*
Retrospective Studies
T-Lymphocytes*
Antigens, CD7

Figure

• 

  Fig. 1 Study design flowchart for classification of HLH patients.*HLH patients were identified according to the 2004 criteria [13]; †>2,000 genome copies/mL of serum; ‡Three familial HLH cases were diagnosed as type 3 familial HLH based on detection of pathogenic variants of the UNC13D gene.Abbreviations: HLH, hemophagocytic lymphohistiocytosis; EBV, Epstein-Barr virus; EBER-ISH, Epstein-Barr encoding region in situ hybridization; BM, bone marrow; MDS, myelodysplastic syndromes; LPD, lymphoproliferative disease.

• 

  Fig. 2 Representative flow cytometric findings in HLH patients. Red and green colors indicate CD8+ T cells and CD4+ T cells, respectively.(A) CD5 downregulation on CD8+ T cells in EBV-positive HLH. (B) CD7 downregulation on CD8+ T cells in EBV-negative secondary HLH. (C) CD5 downregulation on CD8+ T cells in familial HLH.Abbreviations: HLH, hemophagocytic lymphohistiocytosis; EBV, Epstein-Barr virus.

• 

  Fig. 3 Kaplan-Meier survival analysis of HLH patients based on the presence of an aberrant T cell immunophenotype. (A) Overall survival of all HLH patients. (B) Overall survival of EBV-positive HLH patients. (C) Overall survival of EBV-negative secondary HLH patients.Abbreviations: HLH, hemophagocytic lymphohistiocytosis; EBV, Epstein-Barr virus.

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