Anti-idiotypic antibodies to anti-DR in patients with rheumatoid arthritis

Rheumatoid arthritis (RA) sera were evaluated for anti-idiotypic (anti-id) antibodies to HLA-DR antigens (anti-DR) using an ELISA method with murine monoclonal anti-DR antibody-coated microtiter plates incubated serially with either normal or RA sera and peroxidase-conjugated goat anti-human IgG (Fc specific). Specificity was examined using other monoclonal antibodies including anti-Leu 3a, OKM5, OKT8, anti-cytochrome c, and anti-breast tumor antigen. Significant binding of 11/33 (33%) RA to anti-DR was found compared with 0/44 normals (P less than 0.001). Two groups were identified: RA sera reacting with anti-DR and anti-Leu 3a and sera which did not bind to anti-DR but bound to irrelevant monoclonal antibodies. Anti-DR reactivity was differentiated from anti-Leu 3a by competitive inhibition studies. Binding of whole sera and IgG from RA patients to anti-DR was significantly inhibited by DR+ cell extract. The same extract was not inhibitory after selective removal of DR antigen by adsorption on an anti-DR-Sepharose column. These data suggest that anti-id antibodies are directed against the antigen-binding site of id. We conclude that some RA patients have anti-id antibodies potentially involved in immunoregulation of anti-DR antibodies.