title: Noninherited maternal antigens do not play a role in rheumatoid arthritis susceptibility in Europe. European Consortium on Rheumatoid Arthritis Families.
abstract: OBJECTIVE
  It has been proposed that noninherited maternal antigens (NIMA) (HLA-DR antigens) might play a role in susceptibility to rheumatoid arthritis (RA), especially in patients who are not genetically predisposed, such as those who are HLA-DR4 and/or shared epitope (SE) negative. The present study was undertaken to test the NIMA hypothesis in a large cohort of European RA patients assembled by the European Consortium on RA Families (ECRAF).
  
  
  METHODS
  HLA-DRB1 oligotyping was performed in families of European RA patients for whom both parents were alive. These families were consecutively recruited by the ECRAF between 1996 and 1998, for association studies. The frequencies of HLA-DR NIMA were compared with those of the noninherited paternal antigens (NIPA) after stratification for HLA-DR*04, *0401 and/or *0404, and SE status. NIMA or NIPA that coincided with inherited HLA-DR antigens were considered redundant and excluded from analysis. Calculations concerning the whole group and restricted to patients lacking parental RA were performed.
  
  
  RESULTS
  One hundred seventy families from France (n = 81), Belgium (n = 23), Spain (n = 24), Italy (n = 19), Portugal (n = 14), and The Netherlands (n = 9) were oligotyped. The group of probands was predominantly female (88%), positive for rheumatoid factor, DR*04, and SE (71%, 58%, and 75%, respectively), and had erosive disease (75%). Parental RA was reported in 21 families. Using the NIPA as control, the frequency of HLA-DRB1*04, *0401 and/or *0404-, or SE-positive NIMA was not found to be increased in patients lacking these susceptibility alleles. The same was true when the 21 probands with parental RA were excluded from analysis. In DRB1*04-positive patients, we found no evidence of a relevant effect of HLA-DR3 or DR6 in the NIMA.
  
  
  CONCLUSIONS
  Our results do not support the notion that noninherited maternal antigens have a role in susceptibility to RA in the offspring.
authors.affiliation: Department of Rheumatology, University Hospital, Nijmegen, The Netherlands.
authors.forename: P
authors.initials: P
authors.lastname: Barrera
authors.forename: A
authors.initials: A
authors.lastname: Balsa
authors.forename: H
authors.initials: H
authors.lastname: Alves
authors.forename: R
authors.initials: R
authors.lastname: Westhovens
authors.forename: K
authors.initials: K
authors.lastname: Maenaut
authors.forename: F
authors.initials: F
authors.lastname: Cornélis
authors.forename: P
authors.initials: P
authors.lastname: Fritz
authors.forename: T
authors.initials: T
authors.lastname: Bardin
authors.forename: G
authors.initials: G
authors.lastname: de Almeida
authors.forename: A
authors.initials: A
authors.lastname: Lopes-Vaz
authors.forename: D
authors.initials: D
authors.lastname: Pascual Salcedo
authors.forename: E G
authors.initials: EG
authors.lastname: de la Concha
authors.forename: T R
authors.initials: TR
authors.lastname: Radstake
authors.forename: L B
authors.initials: LB
authors.lastname: van de Putte
authors.forename: P
authors.initials: P
authors.lastname: Migliorini
authors.forename: J F
authors.initials: JF
authors.lastname: Prud'homme
authors.forename: D
authors.initials: D
authors.lastname: Charron
authors.forename: M
authors.initials: M
authors.lastname: Spyropoulou
authors.forename: A
authors.initials: A
authors.lastname: Mendes
authors.forename: M
authors.initials: M
authors.lastname: Spaepen
authors.forename: M
authors.initials: M
authors.lastname: Martinez
authors.forename: V
authors.initials: V
authors.lastname: Lepage
authors.forename: C
authors.initials: C
authors.lastname: Stravopoulos
mesh_terms: D000328:Adult; D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology*; D015331:Cohort Studies; D005060:Europe; D005192:Family Health; D005260:Female; D006684:HLA-DR Antigens / Q000235:genetics*; D006650:Histocompatibility Testing; D006801:Humans; D008297:Male; D009426:Netherlands / Q000453:epidemiology; D015995:Prevalence
chemical_list: D006684:HLA-DR Antigens