title: Reduced proportions of natural killer T cells are present in the relatives of lupus patients and are associated with autoimmunity.
abstract: BACKGROUND
  Systemic lupus erythematosus is a genetically complex disease. Currently, the precise allelic polymorphisms associated with this condition remain largely unidentified. In part this reflects the fact that multiple genes, each having a relatively minor effect, act in concert to produce disease. Given this complexity, analysis of subclinical phenotypes may aid in the identification of susceptibility alleles. Here, we used flow cytometry to investigate whether some of the immune abnormalities that are seen in the peripheral blood lymphocyte population of lupus patients are seen in their first-degree relatives.
  
  
  METHODS
  Peripheral blood mononuclear cells were isolated from the subjects, stained with fluorochrome-conjugated monoclonal antibodies to identify various cellular subsets, and analyzed by flow cytometry.
  
  
  RESULTS
  We found reduced proportions of natural killer (NK)T cells among 367 first-degree relatives of lupus patients as compared with 102 control individuals. There were also slightly increased proportions of memory B and T cells, suggesting increased chronic low-grade activation of the immune system in first-degree relatives. However, only the deficiency of NKT cells was associated with a positive anti-nuclear antibody test and clinical autoimmune disease in family members. There was a significant association between mean parental, sibling, and proband values for the proportion of NKT cells, suggesting that this is a heritable trait.
  
  
  CONCLUSIONS
  The findings suggest that analysis of cellular phenotypes may enhance the ability to detect subclinical lupus and that genetically determined altered immunoregulation by NKT cells predisposes first-degree relatives of lupus patients to the development of autoimmunity.
authors.affiliation: Arthritis Centre of Excellence, Division of Genetics and Development, Toronto Western Hospital Research Institute, University Health Network, Toronto, Ontario, Canada. jwither@uhnres.utoronto.ca
authors.forename: Joan
authors.initials: J
authors.lastname: Wither
authors.forename: Yong-chun
authors.initials: YC
authors.lastname: Cai
authors.forename: Sooyeol
authors.initials: S
authors.lastname: Lim
authors.forename: Tamara
authors.initials: T
authors.lastname: McKenzie
authors.forename: Nicole
authors.initials: N
authors.lastname: Roslin
authors.forename: Jaime O
authors.initials: JO
authors.lastname: Claudio
authors.forename: Glinda S
authors.initials: GS
authors.lastname: Cooper
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Hudson
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Paterson
authors.forename: Celia M T
authors.initials: CM
authors.lastname: Greenwood
authors.forename: Dafna
authors.initials: D
authors.lastname: Gladman
authors.forename: Janet
authors.initials: J
authors.lastname: Pope
authors.forename: Christian A
authors.initials: CA
authors.lastname: Pineau
authors.forename: C Douglas
authors.initials: CD
authors.lastname: Smith
authors.forename: John G
authors.initials: JG
authors.lastname: Hanly
authors.forename: Christine
authors.initials: C
authors.lastname: Peschken
authors.forename: Gilles
authors.initials: G
authors.lastname: Boire
authors.forename: Paul R
authors.initials: PR
authors.lastname: Fortin
mesh_terms: D000328:Adult; D000974:Antibodies, Antinuclear / Q000097:blood; D015703:Antigens, CD / Q000378:metabolism; D015551:Autoimmunity / Q000276:immunology*; D005190:Family; D005260:Female; D005434:Flow Cytometry; D020022:Genetic Predisposition to Disease; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000235:genetics* / Q000276:immunology*; D008297:Male; D055611:Natural Killer T-Cells / Q000276:immunology*; D010375:Pedigree; D010641:Phenotype
chemical_list: D000974:Antibodies, Antinuclear; D015703:Antigens, CD
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