Measurement of Rheumatoid Factor Isotypes in the Clinical Laboratory

Abstract

In this study we assessed the clinical utility of measuring all major rheumatoid factor (RF) isotypes (IgG, IgA, and IgM) in the diagnostic immunology laboratory using an enzyme-linked immunoassay (ELISA). An improved method for IgG-RF was tested which employed a commercially available monoclonal anti-human IgG Fd antibody and did not require pepsin digestion of samples. We detected elevated levels of all three RF isotypes in a population of hospitalized rheumatoid arthritis patients (n=109). We demonstrated a significant association between IgM and IgA RF which occurred in 36% of our subjects, while less than 6% had IgM + IgG RF or IgG + IgA RF. A comparison of the IgM ELISA with the Rheuruaton revealed a statistically significant correlation (r=0.65, p=0.0001). In addition, the two methodologies were equivalent in sensitivity (ELISA: 76%, Rheumaton: 78%). However, the ELISA procedure was more time consuming, costly, and required greater technical expertise. The following clinical and laboratory findings were significantly associated with RF isotypes: IgG RF and the presence of rheumatoid nodules (p=0.03), elevated erythrocyte sedimentation rate (ESR) and IgG RF (p=0.007), and elevated ESR and IgM RF (p=0.0009). Our ELISA methodology did not provide significant advantages over existing techniques to justify its use as part of the routine laboratory assessment of rheumatoid factor.