title: Sialic acid cyclization of human Th homing receptor glycan associated with recurrent exacerbations of atopic dermatitis.
abstract: BACKGROUND
  The molecular pathogenesis underlying recurrent exacerbations of atopic dermatitis (AD) is unclear. Some peripheral CCR4(+) and CCR7(+) helper memory T cells express the specific homing receptor, sialyl 6-sulfo Lewis X (G152 glycan). This glycan loses receptor activity via cyclization of its sialic acid moiety, thus becoming cyclic sialyl 6-sulfo Lewis X (G159 glycan). These findings suggest that the disordered expression of G152 and G159 glycans may be associated with recurrent exacerbations of AD.
  
  
  OBJECTIVE
  To assess the possible association of G152 and G159 glycans, which are expressed on peripheral helper T (Th) cells, with frequency of exacerbations.
  
  
  METHODS
  The percentage of glycan-expressing cells among peripheral blood CD4(+)CD45RO(+) lymphocytes was determined by flow cytometry. The association of glycans with the frequency of exacerbations determined by recurrence scores as well as with current disease activity was statistically tested.
  
  
  RESULTS
  Current disease activity was significantly associated with CCR4(+)CCR7(-) memory Th cells expressing CSLEX-1 glycan, the conventional skin-trafficking receptor without sialic-acid-cyclization activity. In contrast, the frequency of exacerbations was positively and negatively associated with CCR4(+)CCR7(+) memory Th cells expressing G152 and G159 glycans, respectively. Receiver operating characteristics analyses indicated that the ratio of the G152(+)/G159(+) cell percentages discriminated patients with highly recurrent AD with the best accuracy.
  
  
  CONCLUSIONS
  Flow cytometric determination of G159 and G152 glycans on peripheral helper memory T cells may be clinically useful for identifying patients with highly recurrent AD. Disordered sialic acid cyclization of G152 glycan may underlie highly recurrent AD, which may provide a novel therapeutic approach.
authors.affiliation: Division of Molecular Pathology, Aichi Cancer Center, Nagoya, Aichi 464-8681, Japan.
authors.forename: Keiichiro
authors.initials: K
authors.lastname: Sakuma
authors.forename: Takuya
authors.initials: T
authors.lastname: Furuhashi
authors.forename: Sachiko
authors.initials: S
authors.lastname: Kondo
authors.forename: Uichiro
authors.initials: U
authors.lastname: Yabe
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Ohmori
authors.forename: Hidemi
authors.initials: H
authors.lastname: Ito
authors.forename: Masahiro
authors.initials: M
authors.lastname: Aoki
authors.forename: Akimichi
authors.initials: A
authors.lastname: Morita
authors.forename: Reiji
authors.initials: R
authors.lastname: Kannagi
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D003500:Cyclization; D003876:Dermatitis, Atopic / Q000209:etiology / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D006801:Humans; D007156:Immunologic Memory; D016256:Lewis X Antigen / Q000031:analogs & derivatives; D008297:Male; D008875:Middle Aged; D019158:N-Acetylneuraminic Acid / Q000737:chemistry; D009844:Oligosaccharides / Q000737:chemistry / Q000378:metabolism; D054398:Receptors, CCR4 / Q000378:metabolism; D054400:Receptors, CCR7 / Q000378:metabolism; D016201:Receptors, Lymphocyte Homing / Q000737:chemistry / Q000378:metabolism*; D012008:Recurrence; D000080506:Sialyl Lewis X Antigen / Q000031:analogs & derivatives; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism*; D055815:Young Adult
chemical_list: C086949:6'-sulfated sialyl Lewis x; C515354:CCR4 protein, human; C515370:CCR7 protein, human; D016256:Lewis X Antigen; D009844:Oligosaccharides; D054398:Receptors, CCR4; D054400:Receptors, CCR7; D016201:Receptors, Lymphocyte Homing; D000080506:Sialyl Lewis X Antigen; D019158:N-Acetylneuraminic Acid