[Present status and problems with rheumatoid factor as a laboratory test]

Rheumatoid factor(RF) has generally been defined as antibodies against mammalian IgG Fc. In a majority of patients with rheumatoid arthritis(RA), RF can be regarded as an autoantibody because it binds to their own IgG. RF in RA, however, can bind to various other IgG antigens such as IgG allotypic antigens(Gm), isoallotypic antigens, species-specific IgG antigens, cross-reactive antigens shared by other mammalian IgG and neoantigens created within IgG by immune-complex formation. This multi-specific characterization of RF has caused interlaboratory variation and it has been difficult to conduct external quality assessment(EQA) using various qualitative and/or quantitative RF kits. In the future, RF measurement should be assessed by each kit's EQA. It is significant to make a distinction between the pathological and non-pathological roles of RF owing to improvement of vagueness in clinical evaluation of RF measurement. Complement activation by RF, measurement of functional affinity(avidity) and quantitative determination of IgG and/or IgA RF have been investigated by us and other investigators for evaluation of RF's pathological role. Quantitative determination of RF's physiological, innate and non-pathological role is so important in health and disease that we have developed IgM-class antiglobulin against neoantigens appearing not in heat-aggregated human IgG but in human IgG bound to antigen.