Serum IgG4 anti-Fab antibodies in rheumatoid arthritis are constitutively expressed

IgG4 comprises a significant proportion of the total anti-Fab antibody (aFABA) response in many but not all patients with rheumatoid arthritis (RA). Analyses of the dynamics of IgG aFABA subclass expression in 11 RA patients for periods of up to 11 months demonstrated that IgG4 aFABA was restricted to 6 of the 11 RA patients' sera initially studied and comprised approximately 25% (or more) of the total IgG aFABA response. Quantities of IgG4 aFABA in subsequent, serially obtained serum samples from these patients remained stable throughout the study period, whereas the remaining RA patients whose initial sera possessed small quantities of serum IgG4 aFABA failed to generate any augmented IgG4 aFABA response during the study. Elevated expression of IgG4 aFABA did not appear to be a consequence of a generalized polyclonal gammopathy or a generalized increase in autoantibody expression, though patients with higher total IgG4 serum levels expressed significantly greater quantities of IgG4 aFABA. These results indicate that the differential expression of IgG4 aFABA among RA patients reflects constitutive production within a subset of RA patients in whom IgG4 appears to comprise a significant proportion of the total IgG aFABA response.