title: Brief Report: HLA-DRB1, DQA1, and DQB1 in Juvenile-Onset Systemic Sclerosis.
abstract: Systemic sclerosis (SSc) is a rare disease that is particularly uncommon in children. Specific HLA alleles have been associated with SSc in adults. This study was undertaken to investigate HLA class II alleles in juvenile-onset SSc.
  
  
  
  DRB1, DQA1, and DQB1 alleles were determined by DNA-based HLA typing. Analyses were conducted comparing Caucasian patients with juvenile-onset SSc (n = 76) to healthy Caucasian controls (n = 581).
  
  
  
  Initial analyses focused on HLA class II associations previously reported in adult Caucasian patients with SSc. The frequency of DRB1*11 was not significantly increased in juvenile-onset SSc (22.4% of patients with juvenile-onset SSc versus 17.6% of controls; odds ratio [OR] 1.35, P = 0.34), nor were the specific DRB1*11:01 or *11:04 alleles. DQA1*05, a risk factor previously identified in adult men with SSc, was increased in patients with juvenile-onset SSc versus controls (57.9% versus 44.1%; OR 1.76, P = 0.027), as was DRB1*03 (34.2% versus 22.5%; OR 1.79, P = 0.031). Secondary analyses of all DRB1 allele groups revealed an association with DRB1*10 (10.5% of patients with juvenile-onset SSc versus 1.5% of controls; OR 7.48, P = 0.0002). As this is a new observation, correction was made for multiple comparisons of 13 different DRB1 allele groups; results nevertheless remained significant (P = 0.003). Also, a lower frequency of DRB1*01 was observed in patients with juvenile-onset SSc who were younger at disease onset (OR 0.06, P = 0.01) and in those with antibodies to topoisomerase (OR 0.14, P = 0.024).
  
  
  
  Associations of HLA alleles with juvenile-onset SSc differed from associations with SSc in women, but were similar to associations with SSc in men. Additionally, a novel association with DRB1*10 was observed in children. The greatest proportion of genetic risk of SSc is contributed by the HLA complex, and the current study reveals the importance of the association of HLA class II genes in juvenile-onset SSc.
authors.affiliation: Seattle Children's Research Institute and University of Washington, Seattle. anne.stevens@seattlechildrens.org.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Stevens
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Sami B
authors.initials: SB
authors.lastname: Kanaan
authors.affiliation: University of Pittsburgh and Children's Hospital of the University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
authors.forename: Kathryn S
authors.initials: KS
authors.lastname: Torok
authors.affiliation: University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Medsger
authors.affiliation: University of Texas Health Science Center at Houston.
authors.forename: Maureen D
authors.initials: MD
authors.lastname: Mayes
authors.affiliation: University of Texas Health Science Center at Houston.
authors.forename: John D
authors.initials: JD
authors.lastname: Reveille
authors.affiliation: Lurie Children's Hospital of Chicago and Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors.forename: Marisa
authors.initials: M
authors.lastname: Klein-Gitelman
authors.affiliation: Duke University School of Medicine, Durham, North Carolina.
authors.forename: Ann M
authors.initials: AM
authors.lastname: Reed
authors.affiliation: Stanford University, Stanford, California and Lucile Packard Children's Hospital, Palo Alto, California.
authors.forename: Tzielan
authors.initials: T
authors.lastname: Lee
authors.affiliation: Hackensack University Medical Center, Hackensack, New Jersey.
authors.forename: Suzanne C
authors.initials: SC
authors.lastname: Li
authors.affiliation: Seattle Children's Research Institute, Seattle, Washington.
authors.forename: Gretchen
authors.initials: G
authors.lastname: Henstorf
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Christine
authors.initials: C
authors.lastname: Luu
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Tessa
authors.initials: T
authors.lastname: Aydelotte
authors.affiliation: Fred Hutchinson Cancer Research Center and University of Washington, Seattle.
authors.forename: J Lee
authors.initials: JL
authors.lastname: Nelson
mesh_terms: D000293:Adolescent; D000483:Alleles; D000974:Antibodies, Antinuclear / Q000276:immunology; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004264:DNA Topoisomerases, Type I / Q000276:immunology; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D059848:HLA-DQ alpha-Chains / Q000235:genetics*; D059866:HLA-DQ beta-Chains / Q000235:genetics*; D059811:HLA-DRB1 Chains / Q000235:genetics*; D006801:Humans; D008297:Male; D016017:Odds Ratio; D010641:Phenotype; D065840:Protective Factors; D012594:Scleroderma, Localized / Q000235:genetics* / Q000276:immunology; D012595:Scleroderma, Systemic / Q000235:genetics* / Q000276:immunology; D044465:White People / Q000235:genetics
chemical_list: D000974:Antibodies, Antinuclear; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; C069050:HLA-DQA1 antigen; C069051:HLA-DQB1 antigen; D059811:HLA-DRB1 Chains; C538950:anticentromere antibody; D004264:DNA Topoisomerases, Type I