Strong association of rheumatoid arthritis with the presence of a polymorphic Ia epitope defined by a monoclonal antibody: comparison with the allodeterminant DR4.

Among individuals with rheumatoid arthritis the presence of the polymorphic Ia antigen epitope detected by the monoclonal antibody 109d6 is more strongly correlated with disease susceptibility than are other specificities, such as HLA DR4, DRw53 (MT3) or the antigenic determinant, defined by the monoclonal antibody 17-3-3S. The cells of 93% of Caucasian and Hispanic patients react with the 109d6 reagent. As was the case in normal individuals, all DR4-positive patients express the 109d6 determinant; however, 26% of those with rheumatoid arthritis have the epitope recognized by antibody 109d6, but lack the specificity DR4. Of these, one-third expresses only HLA DR1 and DQw1 (MT1, MB1) determinants. Studies of family members reveal that here the determinants 109d6, DR1, and DQw1 are encoded by the same unusual haplotype. In certain other individuals with rheumatoid arthritis who express DR4, DRw53, and the 109d6 determinants, family studies show that the 109d6 epitope is encoded not only by the haplotype specifying DR4 but also by the opposite haplotype that does not bear the genes for DR4. This suggests that homozygosity for certain Ia epitopes is relevant to determining the disease-susceptibility state. These studies emphasize the utility of monoclonal antibodies as reagents for the recognition of Ia epitopes that are more closely involved in the determination of disease susceptibility than are allomorphic molecules detected by conventional typing alloantisera.