title: KIR genes and HLA class I ligands in Gaucher disease.
abstract: Gaucher disease (GD) is caused by reduced activity of the lysosomal enzyme glucocerebrosidase, which leads to a buildup of glucocerebroside within the cells and chronic stimulation of the immune system. GD is associated with clinical variability even in the same family, which suggests the influence of modifier genes. Natural killer (NK) cells play an important role in the immune response, and their number is decreased in GD. Killer-cell immunoglobulin-like receptors (KIR) regulate the activity of NK cells through an interaction with specific human leukocyte antigen (HLA) class I molecules on target cells.
  
  
  OBJECTIVE
  To analyze the variability of KIR genes in a sample of GD patients from Southern Brazil, and look for associations between variants and clinical manifestations.
  
  
  METHODS
  Thirty-one GD patients (24 mild, 4 moderate, and 3 severe) were included in the study. Fifteen KIR genes, HLA-C and HLA-Bw4 were analyzed using SSP-PCR. Clinical, biochemical, and radiological data were collected by means of a chart review.
  
  
  CONCLUSIONS
  Age at symptom onset was associated with KIR2DL2 and KIR2DS2 in combination with the ligand HLA-C1 (p=0.038). Patients who have the HLA-C2 variant appear to have more mono- and polyclonal bands on protein electrophoresis (p=0.007, OR 21.3). There was no between-group significant difference in the frequencies of KIR/HLA variants.
  
  
  CONCLUSIONS
  Although exploratory our data suggest a possible association of KIR/HLA variants and the severity of GD. Further study of KIR/HLA variants is required, as they seem to be a phenotype-modifying factor in this disease.
authors.affiliation: Medical Genetics Service, Hospital de Clínicas de Porto Alegre, Brazil. fvairo@hcpa.ufrgs.br
authors.forename: Filippo
authors.initials: F
authors.lastname: Vairo
authors.forename: Pâmela
authors.initials: P
authors.lastname: Portela
authors.forename: Patrícia H
authors.initials: PH
authors.lastname: Salim
authors.forename: Mariana
authors.initials: M
authors.lastname: Jobim
authors.forename: Cristina
authors.initials: C
authors.lastname: Netto
authors.forename: Alicia
authors.initials: A
authors.lastname: Dorneles
authors.forename: Suzana
authors.initials: S
authors.lastname: Mittlestadt
authors.forename: Luiz Fernando
authors.initials: LF
authors.lastname: Jobim
authors.forename: Ida Vanessa D
authors.initials: IV
authors.lastname: Schwartz
mesh_terms: D000293:Adolescent; D000328:Adult; D001938:Brazil; D005260:Female; D005776:Gaucher Disease / Q000235:genetics* / Q000276:immunology; D005787:Gene Frequency; D005805:Genes, MHC Class I / Q000235:genetics*; D014644:Genetic Variation; D005838:Genotype; D015235:HLA-B Antigens / Q000235:genetics / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007694:Killer Cells, Natural / Q000378:metabolism; D008024:Ligands; D008297:Male; D010641:Phenotype; D054340:Receptors, KIR / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
chemical_list: D015235:HLA-B Antigens; C042388:HLA-Bw4 antigen; D015395:Histocompatibility Antigens Class I; D008024:Ligands; D054340:Receptors, KIR