title: Clinical and immunogenetic characteristics of European multicase rheumatoid arthritis families.
abstract: OBJECTIVE
  To describe the characteristics of a new set of European families with affected sib pairs (ASP) collected by the European Consortium on Rheumatoid Arthritis Families (ECRAF) to replicate the results of our first genome scan. Potential gradients for disease severity in Europe and concordance within families were studied.
  
  
  METHODS
  From 1996 to 1998 European white families with at least two affected siblings were enrolled in the study. Demographic (sex, age at onset), clinical data (rheumatoid factor (RF), disease duration, erosive disease, extra-articular features (EF)), and HLA-DRB1 oligotyping were analysed.
  
  
  RESULTS
  565 patients with rheumatoid arthritis (RA), belonging to 271 families including 319 affected sib pairs (ASP) were collected. Belgium, France, Italy, the Netherlands, Portugal, and Spain contributed 20, 96, 52, 24, 9, and 70 families, respectively. Sex (78% women), age at onset (mean 44 years), and RF positivity (79%) were similar among the countries. Differences were found in disease duration (11-18 years) and in the prevalence of erosive disease (70-93%), nodules (15-44%), subjective Sjögren's syndrome (5-38%), and EF (3-16%) (p<0.05 in all cases). A total of 22% RA sibs were shared epitope (SE) negative, whereas 47% and 30% carried one and two SE alleles respectively. Carriage of SE differed widely among countries (p<0.0001): no SE alleles (6-36%), one allele (43-60%), and two alleles (20-39%). SE encoding alleles were mainly DRB1*04 in the Netherlands and Belgium, whereas SE carriage was less common and evenly distributed between DRB1*01, *04, and *10 in Mediterranean countries. No concordance within families was found either in age/calendar year of onset (intraclass correlation coefficient <0.50) or in clinical and radiological features (kappa<0.22).
  
  
  CONCLUSIONS
  The differences in RA characteristics between European countries and within families underline the heterogeneity of the disease. No clear cut gradient of disease severity was seen in Europe.
authors.affiliation: Rheumatology Unit, University Hospital La Paz, 28046 Madrid, Spain. abalsa@hulp.insalud.es
authors.forename: A
authors.initials: A
authors.lastname: Balsa
authors.forename: P
authors.initials: P
authors.lastname: Barrera
authors.forename: R
authors.initials: R
authors.lastname: Westhovens
authors.forename: H
authors.initials: H
authors.lastname: Alves
authors.forename: K
authors.initials: K
authors.lastname: Maenaut
authors.forename: D
authors.initials: D
authors.lastname: Pascual-Salcedo
authors.forename: F
authors.initials: F
authors.lastname: Cornélis
authors.forename: T
authors.initials: T
authors.lastname: Bardin
authors.forename: L
authors.initials: L
authors.lastname: Riente
authors.forename: T R
authors.initials: TR
authors.lastname: Radstake
authors.forename: G
authors.initials: G
authors.lastname: de Almeida
authors.forename: V
authors.initials: V
authors.lastname: Lepage
authors.forename: C
authors.initials: C
authors.lastname: Stravopoulos
authors.forename: M
authors.initials: M
authors.lastname: Spaepen
authors.forename: A
authors.initials: A
authors.lastname: Lopes-Vaz
authors.forename: D
authors.initials: D
authors.lastname: Charron
authors.forename: M
authors.initials: M
authors.lastname: Martinez
authors.forename: J F
authors.initials: JF
authors.lastname: Prudhomme
authors.forename: P
authors.initials: P
authors.lastname: Migliorini
authors.forename: P
authors.initials: P
authors.lastname: Fritz
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000276:immunology; D005060:Europe; D005260:Female; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D006801:Humans; D008297:Male; D008875:Middle Aged; D012217:Rheumatoid Factor / Q000097:blood; D017678:Sex Distribution
chemical_list: D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D012217:Rheumatoid Factor