Noninherited maternal antigens do not play a role in rheumatoid arthritis susceptibility in Europe

Objective. It has been proposed that noninherited maternal antigens (MMA) ( HLA-DR antigens) might play a role in susceptibility to rheumatoid arthriti s (RA), especially in patients who are not genetically predisposed, such as those who are HLA-DR4 and/or shared epitope (SE) negative. The present stu dy 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 pati ents for whom bath parents were alive. These families were consecutively re cruited by the ECRAF between 1996 and 1998, for association studies. The fr equencies of HLA-DR NIMA were compared with those of the noninherited pater nal antigens (NIPA) after stratification for HLA-DR*04, *0401 and/or *0404, and SE status. NIMA or MPA that coincided with inherited HLA-DR antigens w ere considered redundant and excluded from analysis. Calculations concernin g the whole group and restricted to patients lacking parental RA were perfo rmed. 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%, respec tively), and had erosive disease (75%). Parental RA was reported in 21 fami lies. Using the NIPA as control, the frequency of HLA-DRB1*04, *0401 and fo r *0404-, or SE-positive NIMA was not found to be increased in patients lac king these susceptibility alleles. The same was true when the 21 probands w ith 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. Conclusion. Our results do not support the notion that noninherited materna l antigens have a role in susceptibility to RA in the offspring.