Differential patterns of in vitro IgM rheumatoid factor synthesis in seronegative and seropositive rheumatoid arthritis

The existence of a subpopulation of patients with rheumatoid arthritis (RA) who lack detectable rheumatoid factor (RF) is well documented. The cellular basis for nonexpression of RF in seronegative RA is not understood. In order to approach this problem, we compared mononuclear leukocytes (MNL) from 20 healthy adult controls, 20 seropositive RA and 22 seronegative RA patients to assess their capacity to synthesize IgM and IgM RF in vitro in the presence and absence of pokeweed mitogen (PWM). MNL from 10 of 20 seropositive RA patients spontaneously elaborated IgM RF (mean = 16.7 ng/10⁶ cells), whereas this was not observed with MNL from either controls or seronegative patients. Small quantities of IgM were spontaneously released by MNL from the seropositive (68.1 ng/10⁶ cells), seronegative (43.1 ng/10⁶ cells), and control (142.3 ng/10⁶ cells) groups. PWM induced IgM RF production by MNL from 10 of 20 controls (18.5 ng/10⁶ cells) and 8 of 22 seronegative RA patients (13.5 ng/10⁶ cells); however, this was significantly less than the production observed with seropositive RA MNL (13 of 20; 37.5 ng/10⁶ cells). In contrast, IgM production in response to PWM was significantly less in both the seronegative (999.7 ng/10⁶ cells) and seropositive RA groups (471.7 ng/10⁶ cells) than in the control group (2,678 ng/10⁶ cells). IgM RF constituted a significantly higher proportion of total IgM synthesized by seropositive RA MNL (10.7%) than either seronegative RA MNL (2.5%) or control MNL (1.2%). Differences in IgM RF production in vitro could not be explained by HLA—DR4 status. Hidden RF was not detected in seronegative MNL supernatants. The results indicate clear differences in the pattern of in vitro release of IgM and IgM RF by MNL from seronegative RA patients as compared to either seropositive RA MNL or control MNL. The similarity of seronegative RA MNL to control MNL with regard to in vitro expression of IgM RF suggests that regulatory mechanisms governing RF synthesis are relatively intact in patients who have seronegative RA.