title: Association of a functional CD19 polymorphism with susceptibility to systemic sclerosis.
abstract: OBJECTIVE
  CD19 is overexpressed in B cells from patients with systemic sclerosis (SSc), and plays a crucial role not only for autoantibody production, but also for skin fibrosis in mouse models. We previously reported the association of a GT repeat polymorphism in the 3'-untranslated region (3'-UTR) of CD19 with human systemic lupus erythematosus. In this study, we examined whether CD19 polymorphisms are associated with genetic susceptibility to SSc.
  
  
  METHODS
  A case-control association study was performed for CD19 polymorphisms, -499G>T in the promoter region and a GT repeat polymorphism in the 3'-UTR, in 134 patients with SSc and 96 healthy individuals recruited at Kanazawa University. CD19 expression levels in the peripheral blood naive and memory B cells from SSc patients were examined by 2-color flow cytometry.
  
  
  RESULTS
  Carrier frequencies of the -499T allele in the promoter (odds ratio [OR] 2.18, 95% confidence interval [95% CI] 1.31-3.86, P = 0.003) and of the (GT)(14) allele in the 3'-UTR (OR 1.86, 95% CI 1.05-3.28, P = 0.03) were significantly increased in SSc patients compared with healthy controls. Association was particularly evident in patients with limited cutaneous SSc with anticentromere antibodies. These alleles were in linkage disequilibrium, but the -499T allele seemed to play a primary role. CD19 expression levels in peripheral blood B cells were significantly elevated in both naive (P = 0.0029) and memory (P = 0.0022) B cells from patients with SSc who had the -499T allele as compared with those without the -499T allele.
  
  
  CONCLUSIONS
  The CD19 -499G>T polymorphism is associated with higher CD19 expression in B cells, and with susceptibility to SSc.
authors.affiliation: Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. tsuchiya-tky@umin.ac.jp
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Tsuchiya
authors.forename: Kimiko
authors.initials: K
authors.lastname: Kuroki
authors.forename: Manabu
authors.initials: M
authors.lastname: Fujimoto
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Murakami
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Tedder
authors.forename: Katsushi
authors.initials: K
authors.lastname: Tokunaga
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Takehara
authors.forename: Shinichi
authors.initials: S
authors.lastname: Sato
mesh_terms: D000328:Adult; D018941:Antigens, CD19 / Q000235:genetics* / Q000378:metabolism; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007156:Immunologic Memory / Q000235:genetics / Q000276:immunology; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational; D012595:Scleroderma, Systemic / Q000235:genetics* / Q000276:immunology / Q000378:metabolism
chemical_list: D018941:Antigens, CD19