RHEUMATOID-FACTOR AVIDITY IN PATIENTS WITH RHEUMATOID-ARTHRITIS - IDENTIFICATION OF PATHOGENIC RFS WHICH CORRELATE WITH DISEASE PARAMETERS AND WITH THE GAL(0) GLYCOFORM OF IGG

The standard ELISA for measuring rheumatoid factor (RF) binding was mo dified by treatment after the RF-Fc interaction with 2 M guanidine, wh ich allowed a measurement of the avidity of the interaction. Incubatio n with 4 M guanidine eliminated RF binding. There was a direct correla tion (r = 0.99) between the avidity as measured by the modified guanid ine ELISA, and the dissociation constant for monoclonal RFs, as measur ed by competitive ELISA. Of the seropositive rheumatoid arthritis (RA) patients tested, 47% had high-avidity RFs (greater than or equal to 8 % RF binding remaining after guanidine treatment). Tender joint count scores were significantly higher in the high avidity group (p = 0.05), whereas there was no significant difference in the ages, disease dura tion, sedimentation rate, RF titer or serum Ig levels compared to thos e with low-avidity RFs. Additionally 58% of those with high-avidity RF s had subcutaneous nodules, compared to 40% of the low-avidity group. A significantly higher number of nodules was present in the high-avidi ty RF group compared to those with low-avidity RFs (p = 0.03). Interes tingly, the RF avidity was significantly higher in isolated immune com plexes (IC), compared to that in circulating IgM RFs (p = 0.01). The R F avidity correlated with the presence of the glycoform of IgG lacking galactose in both circulating and IC-derived IgG (p = 0.003 and 0.009 respectively). Information about the strength of binding to Fc identi fies a subgroup of IgM RFs that are likely pathological in patients wi th RA, as well as a specific glycoform of the target antigen.