title: The HLA profiles of mixed connective tissue disease differ distinctly from the profiles of clinically related connective tissue diseases.
abstract: OBJECTIVE
  The Norwegian nationwide MCTD cohort was established to obtain unbiased data on key disease issues, and thereby reappraise the concept of MCTD. In the current study, the aims were to obtain detailed HLA profile data on the large Norwegian MCTD cohort and compare these with the HLA profiles of ethnically matched healthy controls and related CTD controls.
  
  
  METHODS
  HLA profiles, determined by sequence-based typing of HLA-B* and DRB1*, were compared between four control groups of Norwegian ancestry, SLE (n = 96), SSc (n = 95), PM/DM (n = 84), healthy individuals (n = 282), the complete MCTD cohort (n = 155) and MCTD subsets defined by key clinical parameters.
  
  
  RESULTS
  HLA-B*08 [odds ratio (OR) 2.05, P = 1.31 × 10(-4)) and DRB1*04:01 (OR 2.82, P = 3.64 × 10(-8)) were identified as risk alleles for MCTD, while DRB1*04:04, DRB1*13:01 and DRB1*13:02 were protective. Risk alleles for SLE and PM/DM were B*08 and DRB1*03:01. SSc risk was associated with DRB1*08:01. Analyses of MCTD subsets identified B*18 [OR 3.32 (95% CI 1.38, 8.01)] and DRB1*03:01 [OR 1.83 (95% CI 1.03, 3.25)] as independent risk factors for lung fibrosis.
  
  
  CONCLUSIONS
  Novel HLA alleles associated with MCTD and disease subsets were identified and DRB1*04:01 was confirmed as a major risk allele. Altogether, the data reinforce the notion of MCTD as a disease entity distinct from SLE, SSc and PM/DM.
authors.affiliation: Department of Medical Genetics, University of Oslo and Oslo University Hospital Ullevål, Rheumatology Unit, Department of Immunology, Oslo University Hospital Rikshospitalet, Oslo and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Siri Tennebø
authors.initials: ST
authors.lastname: Flåm
authors.affiliation: Department of Medical Genetics, University of Oslo and Oslo University Hospital Ullevål, Rheumatology Unit, Department of Immunology, Oslo University Hospital Rikshospitalet, Oslo and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Ragnar
authors.initials: R
authors.lastname: Gunnarsson
authors.affiliation: Department of Medical Genetics, University of Oslo and Oslo University Hospital Ullevål, Rheumatology Unit, Department of Immunology, Oslo University Hospital Rikshospitalet, Oslo and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Torhild
authors.initials: T
authors.lastname: Garen
authors.affiliation: Department of Medical Genetics, University of Oslo and Oslo University Hospital Ullevål, Rheumatology Unit, Department of Immunology, Oslo University Hospital Rikshospitalet, Oslo and Institute of Clinical Medicine, University of Oslo, Oslo, Norway. Department of Medical Genetics, University of Oslo and Oslo University Hospital Ullevål, Rheumatology Unit, Department of Immunology, Oslo University Hospital Rikshospitalet, Oslo and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Benedicte Alexandra
authors.initials: BA
authors.lastname: Lie
authors.affiliation: Department of Medical Genetics, University of Oslo and Oslo University Hospital Ullevål, Rheumatology Unit, Department of Immunology, Oslo University Hospital Rikshospitalet, Oslo and Institute of Clinical Medicine, University of Oslo, Oslo, Norway. Department of Medical Genetics, University of Oslo and Oslo University Hospital Ullevål, Rheumatology Unit, Department of Immunology, Oslo University Hospital Rikshospitalet, Oslo and Institute of Clinical Medicine, University of Oslo, Oslo, Norway. oyvind.molberg@medisin.uio.no.
authors.forename: Øyvind
authors.initials: Ø
authors.lastname: Molberg
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003882:Dermatomyositis / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D006680:HLA Antigens / Q000235:genetics*; D015235:HLA-B Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains / Q000235:genetics; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008947:Mixed Connective Tissue Disease / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics*; D017285:Polymyositis / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics*; D012307:Risk Factors; D012595:Scleroderma, Systemic / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics*; D059467:Transcriptome / Q000235:genetics*; D055815:Young Adult
chemical_list: D006680:HLA Antigens; D015235:HLA-B Antigens; D059811:HLA-DRB1 Chains; C553502:HLA-DRB1*03:01 antigen; C553505:HLA-DRB1*04:01 antigen; C492962:HLA-DRB1*13:01 antigen
keywords: HLA; SLE; U1 small nuclear ribonucleoprotein; connective tissue diseases; genetics; humans; mixed connective tissue disease; myositis; systemic sclerosis