Rheumatoid factor avidity in patients with rheumatoid arthritis: Identification of pathogenic RFs which correlate with disease parameters and with the gal(O) glycoform of IgG

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Abstract
The standard ELISA for measuring rheumatoid factor (RF) binding was modified by treatment after the RF-Fc interaction with 2 M guanidine, which allowed a measurement of the avidity of the interaction. Incubation with 4 M guanidine eliminated RF binding. There was a direct correlation (r= 0.99) between the avidity as measured by the modified guanidine ELISA, and the dissociation constant for monoclonal RFs, as measured by competitive ELISA. Of the seropositive rheumatoid arthritis (RA) patients tested, 47% had high-avidity RFs (≥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 duration, sedimentation rate, RF titer or serum Ig levels compared to those with low-avidity RFs. Additionally 58% of those with high-avidity RFs had subcutaneous nodules, compared to 40% of the low-avidity group. A significantly higher number of nodules was present in the high-avidity RF group compared to those with low-avidity RFs (p=0.03). Interestingly, the RF avidity was significantly higher in isolated immune complexes (IC), compared to that in circulating IgM RFs (p=0.01). The RF 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 identifies a subgroup of IgM RFs that are likely pathological in patients with RA, as well as a specific glycoform of the target antigen.