title: SLURP1 mutation-impaired T-cell activation in a family with mal de Meleda.
abstract: BACKGROUND
  Mal de Meleda (MDM) is palmoplantar erythrokeratoderma with an autosomal recessive inheritance and is caused by a mutation in the gene encoding SLURP-1 (lymphocyte antigen 6/urokinase-type plasminogen activator receptor related protein-1). SLURP-1 is an allosteric agonist to the nicotinic acetylcholine receptor (nAchR) and it regulates epidermal homeostasis. In addition, murine studies have shown that nAchR signalling is important for the regulation of T-cell function. Among the family members, patients with the homozygous SLURP1 (previously known as ARS component B) mutation are prone to melanoma and viral infection, which might link to defective T-cell function as well as a derangement of epidermal homeostasis.
  
  
  OBJECTIVE
  To investigate the association of the SLURP1 gene mutation with T-cell activation in a Taiwanese family with MDM. To test that SLURP-1 is essential for T-cell activation.
  
  
  METHODS
  Human peripheral blood mononuclear cells (PBMCs) were isolated from a Taiwanese MDM family bearing the G to A substitution in nucleotide 256 in the SLURP1 gene, corresponding to a glycine to arginine substitution at amino acid 86 (G86R) in the SLURP-1 protein. PBMCs from homozygotes and wild-type controls were stimulated with anti-CD3/anti-CD28 antibodies and the level of T-cell activation was determined by the stimulation index.
  
  
  RESULTS
  PBMCs with the heterozygous and homozygous SLURP-1 G86R mutation had defective T-cell activation. This was restored by the addition of 0·5 μg mL(-1) recombinant human SLURP-1 protein.
  
  
  CONCLUSIONS
  Patients with MDM with the homozygous SLURP-1 G86R mutation may have an impaired T-cell activation. The presence of wild-type SLURP-1 is essential for normal T-cell activation.
authors.affiliation: Department of Dermatology, National Taiwan University Hospital, Chung-Shan South Road, Taipei 100, Taiwan.
authors.forename: J-W
authors.initials: JW
authors.lastname: Tjiu
authors.forename: P-J
authors.initials: PJ
authors.lastname: Lin
authors.forename: W-H
authors.initials: WH
authors.lastname: Wu
authors.forename: Y-P
authors.initials: YP
authors.lastname: Cheng
authors.forename: H-C
authors.initials: HC
authors.lastname: Chiu
authors.forename: H-Y
authors.initials: HY
authors.lastname: Thong
authors.forename: B-L
authors.initials: BL
authors.lastname: Chiang
authors.forename: W-S
authors.initials: WS
authors.lastname: Yang
authors.forename: S-H
authors.initials: SH
authors.lastname: Jee
mesh_terms: D000368:Aged; D000950:Antigens, Ly / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D015153:Blotting, Western; D018106:CD28 Antigens / Q000097:blood; D017252:CD3 Complex / Q000097:blood; D005260:Female; D006801:Humans; D007645:Keratoderma, Palmoplantar / Q000150:complications / Q000235:genetics / Q000276:immunology; D007911:Lentigo / Q000150:complications / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics*; D008297:Male; D008545:Melanoma / Q000150:complications / Q000473:pathology; D017354:Point Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology*; D013624:Taiwan; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics*; D014860:Warts / Q000150:complications / Q000473:pathology
chemical_list: D000950:Antigens, Ly; D018106:CD28 Antigens; D017252:CD3 Complex; C048963:SLURP1 protein, human; D014568:Urokinase-Type Plasminogen Activator