Testing for isotypes does not help differentiating rheumatoid arthritis from other rheumatoid factor positive diseases

Rheumatoid factors (RFs) are useful for diagnosis and classification of rheumatoid arthritis (RA). Nephelometric and turbidimetric techniques, which detect total RF but do not reveal the antibody isotype, are common diagnostic methods in clinical routine. Given the recent development of isotype-specific immunoassays, the detection of IgG, IgM, and IgA RFs represents an interesting challenge. The aim of the study was to evaluate whether specific RF tests performed as a second step after traditional nephelometry could help differentiating RA from other RF-positive diseases. We tested 117 consecutive serum samples that were RF-positive at nephelometry (BNII nephelometric analyzer, Siemens) for IgA, IgG, and IgM RF isotypes by a fluoroimmunoenzymatic assay (FEIA) on the Phadia 250 instrument (ThermoFisher). Fifty-five subjects had RA and 62 presented non-RA diagnoses. Eighteen sera (15.4%) were positive only by nephelometry, two were positive only for IgA RF, and the remaining 97 sera were all positive for IgM RF isotype (with or without IgG and IgA RF). Positive findings did not correlate with RA or non-RA diagnosis. Spearman rho correlation coefficient between nephelometric total RF and IgM isotype was moderate (0.657), and weak between total RF and IgA (0.396) and IgG (0.360) isotypes. Despite its low specificity, measurement of total RF by nephelometry still seems to be the method that performs best. As IgM, IgA, and IgG RF isotypes showed only a moderate correlation with total RF measurement, their diagnostic use as a second level test remains controversial.