PD-1 improves accurate detection of Sezary cells by flow cytometry in peripheral blood in mycosis fungoides/Sezary syndrome

Cytometry B Clin Cytom. 2022 May;102(3):189-198. doi: 10.1002/cyto.b.22070. Epub 2022 Apr 22.

Abstract

Background: Accurate Sezary cell detection in peripheral blood of mycosis fungoides/Sezary syndrome (MF/SS) patients by flow cytometry can be difficult due to overlapping immunophenotypes with normal T cells using standard markers. We assessed the utility of programmed death-1 (PD-1/CD279), a transmembrane protein expressed in some hematopoietic cells, for identification and quantitation of circulating Sezary cells among established markers using flow cytometry.

Methods: 50 MF/SS and 20 control blood samples were immunophenotyped by flow cytometry. Principal component analysis (PCA) assessed contributions of antigens to separation of abnormal from normal T cell populations. PD-1 was assessed over time in blood and bone marrow of available MF/SS cases.

Results: Normal CD4+ T cells showed dim/intermediate to absent PD-1 expression. PD-1 in Sezary cells was informatively brighter (≥1/3 log) than internal normal CD4+ T cells in 39/50 (78%) cases. By PCA, PD-1 ranked 3rd behind CD7 and CD26 in population separation as a whole; it ranked in the top 3 markers in 32/50 (64%) cases and 1st in 4/50 (8%) cases when individual abnormal populations were compared to total normal CD4+ T cells. PD-1 clearly separated Sezary from normal CD4+ T cells in 15/26 (58%, 30% of total) cases with few and subtle alterations of pan-T cell antigens/CD26 and was critical in 6 (12% of total), without which identification and quantification were significantly affected or nearly impossible. PD-1 remained informative in blood/bone marrow over time in most patients.

Conclusions: PD-1 significantly contributes to accurate flow cytometric Sezary cell assessment in a routine Sezary panel.

Keywords: PD-1; Sezary syndrome; flow cytometry; mycosis fungoides.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers
  • Dipeptidyl Peptidase 4
  • Flow Cytometry
  • Humans
  • Mycosis Fungoides* / diagnosis
  • Programmed Cell Death 1 Receptor
  • Sezary Syndrome* / diagnosis
  • Skin Neoplasms* / diagnosis

Substances

  • Biomarkers
  • Programmed Cell Death 1 Receptor
  • Dipeptidyl Peptidase 4