Objective
HLA-DRB1 alleles encoding the shared epitope (SE) are associated with rheumatoid arthritis (RA) but the underlying biological mechanism is unknown. Several case–control studies have been published on the protective effect of particular SE negative alleles, according to the physicochemical properties of the fourth antigenic peptide binding pocket (P4). The present study was undertaken to test those hypotheses taking advantage of a familial based association analysis.