Rheumatoid factors from patients with rheumatoid arthritis possess private repertoires of idiotypes

Considerable interest has focused on idiotypic cross-reactivity among antibody molecules. Cross-reactive idiotypes (Id) on monoclonal and polyclonal rheumatoid factors (RF) have been found frequently. Sufficient attention has not been directed, however, to the proportion of RF exhibiting the cross-reactivity, leaving the impression of extensive RF cross-reactivity when, in fact, this might represent a small minority of total RF molecules in a given individual. We have examined the polyclonal RF from patients with rheumatoid arthritis (RA) for cross-reactive Id in three different assays and with different Id-anti-Id systems. First, a sensitive liquid-phase radioimmunoassay was used in which panels of sera were tested for inhibition of different, idiotypically unrelated, Id-anti-Id interactions. When compared with normal sera, some of the sera from patients with RA caused minimal inhibition of Id-anti-Id interactions. None, however, caused marked inhibition of any Id-anti-Id system. Secondly, the panels of sera were also tested in a direct binding ELISA to detect partially cross-reactive Id that may not have been identified in the inhibition radioimmunoassay without differing results. Finally, results similar to the autologous Id-anti-Id inhibition assay were also found when the panels of RA sera were tested in two nonautologous Id-anti-Id systems, in which the anti-Id reacted with other than their own Id. These studies indicate that although cross-reactivity with some RF of an individual's total RF population may be seen frequently, an individual's repertoire of RF is itself private, quite diverse, and unique to that individual.