HUMAN MONOCLONAL RHEUMATOID FACTORS - INCIDENCE OF CROSS-REACTIONS WITH TISSUE-COMPONENTS AND CORRELATION WITH V-H GENE USAGE

Human monoclonal antibodies with rheumatoid factor (RF) activity, deri ved from lymphocytes from the synovial tissue of rheumatoid arthritis (RA) patients and the peripheral blood of healthy individuals were exa mined for cross-reactivity with tissue and cellular antigens. The majo rity of IgM RF from RA patients (68%) showed reactivity with at least one component, and were frequently multispecific. A very significantly smaller proportion (28%) of the RF derived from healthy individuals d emonstrated reactivities against tissue/cellular antigens (P = 0.004). RF from RA patients most commonly reacted with gastric glands (61%), nuclei (50%) and smooth muscle (50%), whereas RF from healthy donors m ost commonly reacted with gastric glands (20%), smooth muscle (16%), e ndothelium (16%) and glomeruli (16%). The most striking difference bet ween the two groups was the reactivity with nuclear components, demons trated by 50% of the RA RF, but by none of the healthy donor RF. As th e two groups of antibodies share the same specificity for IgG Fc, but show differences in variable region segment usage, we investigated the relationship between V-H gene usage and tissue/cell cross-reactivity using these antibodies and anti-blood group antibodies. Antibodies usi ng V(H)3 or V(H)4 gene segments showed a very significantly greater fr equency of tissue/cell reactions than those using V(H)1 (P = 0.0095 an d 0.0004 respectively).