Idiotypic network: possible explanation of seronegativity in a patient with rheumatoid arthritis

In order to explain long term seronegativity in certain patients with rheumatoid arthritis (RA), we looked for the presence of anti-idiotypic antibodies against rheumatoid factors (RFs). From a patient's serum with classical but seronegative RA, we isolated a low quantity of the IgG fraction which partially recognized polyclonal RF idiotypes. The purified Fab'2 anti-idiotypic antibodies were able to inhibit up to 48% of in vitro RF production by pokeweed mitogen stimulated lymphocytes from a patient's peripheral blood with seropositive RA. The two main conclusions of this study are: (1) this single patient with seronegative RA has serum antibodies directed against RF idiotypes and (2) these anti-idiotypic antibodies could be implicated in the generation of seronegativity.