Why a positive rheumatoid factor test does not always mean rheumatoid arthritis
Luc Van Kaer
Luc Van Kaer
View: Text | PDF
Commentary

Why a positive rheumatoid factor test does not always mean rheumatoid arthritis

Abstract

Rheumatoid factors (RFs) are autoantibodies directed against the tail region of IgG antibodies and are present in a majority of people with rheumatoid arthritis (RA). RF production is commonly assessed to help diagnose RA, but its performance is limited due to low specificity and sensitivity for reasons that have remained unclear. In this issue of the JCI, Hocaoğlu and Sawalha shed light on this matter using extensive phenome-, genome-, transcriptome-, and proteome-wide association analyses of RF-seropositive and -seronegative individuals. They report that RF production was controlled by a genetic signature that included HLA and non-HLA genes and an immune signature reflective of B cell dysregulation but distinct from the genetic and immune signatures associated with RA. These findings explain the limited diagnostic value of RF testing in RA and may help refine the clinical management of RA and development of interventions that prevent or delay disease.

Authors

Luc Van Kaer

×

Figure 1

Genetic, environmental, and immune factors associated with asymptomatic RF production compared with RA.

Options: View larger image (or click on image) Download as PowerPoint
Genetic, environmental, and immune factors associated with asymptomatic ...
Hocaoğlu and Sawalha (13) compared the genetic and systemic immune signatures of RF production in asymptomatic individuals (left) with the established genetic and peripheral immune signatures of patients with RA (right). In addition to differences in the genetic loci associated with either group, the study determined that RF production in genetically susceptible individuals may be associated with environmental factors such as smoking and certain infections that mediate mucosal inflammation. Over time, RF levels may rise and include non-IgM isotypes. In individuals who are also genetically susceptible to RA development, environmental factors such as infections may trigger progression toward RA and rapid induction of the systemic RA immune signature, which commonly includes production of ACPAs.