Routine measurement of IgM, IgG, and IgA rheumatoid factors: high sensitivity, specificity, and predictive value for...

To determine the isotype specificity and clinical utility of routine testing by ELISA of IgM, IgG, and IgA rheumatoid factors (RF).

The test was performed on 619 individual specimens: blood bank donors (n = 130); rheumatoid arthritis (RA, n = 139); connective tissue diseases (CTD, n = 71); miscellaneous rheumatic disorders (MRD, n = 91); and 188 consecutive clinical laboratory specimens that tested positive by latex agglutination. Rabbit IgG was used as the antigen attached to the solid phase, and rabbit IgG antibody-enzyme conjugates against IgM (Fc5mu), IgG[F(ab')2], and IgA (alpha chain) were used, respectively, to detect IgM, IgG, and IgA RF. The serum was digested with pepsin to facilitate the measurement of IgG RF.

All 3 isotypes were specifically identified; IgM RF was destroyed by pepsin and IgG RF was specifically measured, without interference from IgA RF. Using data obtained from 98 RA specimens and 162 disease controls, the 3 main clinical variables--sensitivity, specificity, and predictive value--were stratified according to 3 combinations of RF isotypes: IgM only (91, 76, and 62%); IgM+IgA (79, 89, and 80%), and IgM+IgG+IgA (53, 99, and 96%). For patients with the 3 isotypes plus > 150 U of IgM and/or IgA the clinical variables were 70, 97, and 93%. In patients with RA the IgG RF was found only in association with IgM RF, i.e., there was no "hidden" RF, and IgA RF was always accompanied by IgM RF. There was a continuous decline in all 3 RF isotypes during treatment with gold salts. The sensitivity of ELISA for IgM RF exceeded that of nephelometry or latex agglutination.

Routine measurement of IgM, IgG, and IgA RF by ELISA with rabbit IgG as the antigen and pepsin digestion for the detection of IgG RF provides useful information in the differential diagnosis of patients with arthritis.