title: CD158k is a reliable marker for diagnosis of Sézary syndrome and reveals an unprecedented heterogeneity of circulating malignant cells.
abstract: The diverse aspects of cutaneous T-cell lymphomas may impede the diagnosis of Sézary syndrome (SS) and mycosis fungoides (MF), in particular, at early stages of the disease. We defined the CD158k/KIR3DL2 molecule as a first positive cell surface marker for Sézary cells (SCs). Here, we designed an optimized flow cytometry gating strategy, allowing the definition of lymphocytes of different sizes and defects of cell surface markers. Quantification by cytomorphology, flow cytometry, or clonal evaluation, gave similar results at initial time points and during the evolution in a prospective study involving 64 consecutive cutaneous T-cell lymphoma or erythrodermic patients. We found that CD158k+ T cells and circulating CD4+ T cells from MF patients exhibited unexpected patterns of cell surface expression with a marked heterogeneity of circulating lymphocytes even at initial diagnosis. Taken together, our results show that a multistep gating of CD158k+ cells is reliable to assess tumor burden in case of SS and suggest that both circulating MF CD4+ T cells and CD158k+ T cells are not homogeneous distinct memory populations. Further phenotypic and functional characterizations of such subsets are needed to better understand the underlying molecular mechanisms leading to the development of these diseases.
authors.affiliation: INSERM UMR-1160, Institut Universitaire d'Hématologie, Paris, France; University of Paris Diderot, Sorbonne Paris Cité, Paris, France; Laboratoire d'Immunologie-Histocompatibilité, Hôpital Saint Louis, AP-HP, Paris, France. Electronic address: helene.moins@univ-paris-diderot.fr.
authors.forename: Hélène
authors.initials: H
authors.lastname: Moins-Teisserenc
authors.affiliation: INSERM UMR-1160, Institut Universitaire d'Hématologie, Paris, France.
authors.forename: Magali
authors.initials: M
authors.lastname: Daubord
authors.affiliation: INSERM UMR-1160, Institut Universitaire d'Hématologie, Paris, France; University of Paris Diderot, Sorbonne Paris Cité, Paris, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Clave
authors.affiliation: INSERM UMR-1160, Institut Universitaire d'Hématologie, Paris, France; University of Paris Diderot, Sorbonne Paris Cité, Paris, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Douay
authors.affiliation: INSERM UMR-1160, Institut Universitaire d'Hématologie, Paris, France; University of Paris Diderot, Sorbonne Paris Cité, Paris, France.
authors.forename: Joana
authors.initials: J
authors.lastname: Félix
authors.affiliation: University of Paris Diderot, Sorbonne Paris Cité, Paris, France; INSERM UMR-976, UFR de Médecine, Paris, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Marie-Cardine
authors.affiliation: University of Paris Diderot, Sorbonne Paris Cité, Paris, France; INSERM UMR-976, UFR de Médecine, Paris, France; Service de Dermatolgie, Hôpital Saint Louis, AP-HP, Paris, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Ram-Wolff
authors.affiliation: Laboratoire d'Immunologie-Histocompatibilité, Hôpital Saint Louis, AP-HP, Paris, France.
authors.forename: Guitta
authors.initials: G
authors.lastname: Maki
authors.affiliation: Laboratoire d'Hématologie, Hôpital Saint Louis, AP-HP, Paris, France.
authors.forename: Kheira
authors.initials: K
authors.lastname: Beldjord
authors.affiliation: Laboratoire d'Immunologie-Histocompatibilité, Hôpital Saint Louis, AP-HP, Paris, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Homyrda
authors.affiliation: University of Paris Diderot, Sorbonne Paris Cité, Paris, France; INSERM UMR-976, UFR de Médecine, Paris, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Michel
authors.affiliation: University of Paris Diderot, Sorbonne Paris Cité, Paris, France; INSERM UMR-976, UFR de Médecine, Paris, France. Electronic address: armand.bensussan@inserm.fr.
authors.forename: Armand
authors.initials: A
authors.lastname: Bensussan
authors.affiliation: INSERM UMR-1160, Institut Universitaire d'Hématologie, Paris, France; University of Paris Diderot, Sorbonne Paris Cité, Paris, France; Laboratoire d'Immunologie-Histocompatibilité, Hôpital Saint Louis, AP-HP, Paris, France. Electronic address: antoine.toubert@univ-paris-diderot.fr.
authors.forename: Antoine
authors.initials: A
authors.lastname: Toubert
authors.affiliation: University of Paris Diderot, Sorbonne Paris Cité, Paris, France; INSERM UMR-976, UFR de Médecine, Paris, France; Service de Dermatolgie, Hôpital Saint Louis, AP-HP, Paris, France. Electronic address: martine.bagot@sls.aphp.fr.
authors.forename: Martine
authors.initials: M
authors.lastname: Bagot
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000276:immunology / Q000378:metabolism*; D018450:Disease Progression; D005500:Follow-Up Studies; D018740:Genetic Heterogeneity; D006801:Humans; D007156:Immunologic Memory; D008137:Longitudinal Studies; D016131:Lymphocyte Subsets / Q000378:metabolism; D016410:Lymphoma, T-Cell, Cutaneous / Q000378:metabolism*; D008875:Middle Aged; D009182:Mycosis Fungoides / Q000378:metabolism*; D009360:Neoplastic Cells, Circulating / Q000378:metabolism*; D011446:Prospective Studies; D054343:Receptors, KIR2DL2 / Q000276:immunology / Q000378:metabolism*; D012751:Sezary Syndrome / Q000175:diagnosis* / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; C515077:KIR2DL2 protein, human; D054343:Receptors, KIR2DL2