Women who develop rheumatoid arthritis (RA) have signs of immune activation for up to 12 years before the onset of symptoms, US researchers report.
“A growing body of evidence suggests that RA develops in three phases: an asymptomatic period of genetic risk, a preclinical phase in which RA-related autoantibodies can be detected, and a clinical phase with acute signs and symptoms of inflammatory arthritis,” say Elizabeth Karlson and colleagues from Harvard medical School in Boston, Massachusetts.
In the present study, Karlson and team used samples from two large, prospectively studied cohorts of women (the Women's Health Study [WHS] and the Nurses' Health Study [NHS]) to examine the association between inflammatory markers and preclinical RA.
They tested blood samples, obtained prior to symptom onset in women who later developed RA, for levels of interleukin-6 (IL-6), soluble tumor necrosis factor receptor II (sTNFRII) (as a surrogate marker for TNF), and high-sensitivity C-reactive protein and compared the results with matched controls.
The researchers report that there were 93 incident RA cases in the NHS and 77 incident cases in the WHS, with an average time to onset of symptoms of 5.2 years.
The median IL-6 and sTNFRII levels were significantly higher in preclinical RA cases compared with controls in the NHS group but not in the WHS, which may be due to women in the WHS group having a less severe form of RA, Karlson et al remark.
Pooled analysis of the two cohorts showed that levels of sTNFRII were elevated up to 12 years prior to the development of RA and were associated with a two-fold increased risk for RA. Elevated IL-6 levels were also associated with RA but only less than 4 years before symptom onset.
“Our findings suggest that during the preclinical phase of autoantibody production, there is immune reactivity, with production of pro-inflammatory cytokines that are typically seen in symptomatic RA, namely, IL-6 and TNF,” conclude the researchers in the journal Arthritis and Rheumatism.
“Studies with repeated assessments of biomarkers prior to RA development may provide further insight into the timing of biomarker elevation in preclinical RA,” they add.