The distribution of
HLA-D region
antigens was studied in three groups (I, IIa, and IIb) of patients with
rheumatoid arthritis (RA): group I comprised 43 patients with mild, non-progressive RA, controlled by non-steroidal anti-inflammatory drugs without progression or erosions; group II comprised 94 patients with severe disease, who had earlier been treated with non-steroidal anti-inflammatory drugs and all had incomplete response requiring treatment with
gold (
sodium aurothiomalate). Of these, 46 patients (group IIa) responded to
gold and the disease was well controlled, and the remaining 48 patients (group IIb) did not respond to
gold and developed
gold induced toxic reactions, including
thrombocytopenia or
proteinuria, or both.
HLA-D region
antigens were defined by serological and molecular (Southern blot analysis and
oligonucleotide typing) techniques. The results show that DR4 was significantly increased in all three groups of patients. The prevalence of DR1, or DR1 in DR4 negative patients, and DR3 and DR4 associated DQw7 specificities, however, showed differences in these three groups of patients. The prevalence of DR1 and of DR1 in DR4 negative patients was increased only in patients with mild (group I) RA, but not in patients with severe (groups IIa and IIb) disease. On the other hand, the prevalence of DR4 associated DQw7 was significantly increased in patients with severe disease, but not in patients with mild RA. In addition, DR3 was significantly increased only in patients with severe disease who developed
gold induced toxic reactions (group IIb). These data suggest that the
HLA-D region genes which cause susceptibility to mild RA may be different from those causing susceptibility to severe RA. The results suggest that both DR and DQ (A, B) genes may be important in conferring susceptibility to RA: DR in mild disease and DQ in severe RA.