Rheumatoid arthritis is predicted by mildly increased rheumatoid factor: implications for autoimmunity

Rheumatoid arthritis, like other autoimmune diseases, can be brewing for years before it becomes clinically evident. Research just published in the British Medical Journal shows that a mild elevation in rheumatoid factor reveals increased risk for rheumatoid arthritis long before the classical symptoms are expressed. Low levels of autoantibodies can appear early in the evolution of other autoimmune conditions as well. The authors set out to...

"......test whether elevated concentration of rheumatoid factor is associated with long term development of rheumatoid arthritis."

Autoantibodies are produced by the immune system when it attacks our own tissues. The authors of a linked editorial note:

"Rheumatoid factor is an autoantibody used in the classification of rheumatoid arthritis. It can also be present in other inflammatory conditions and is seen in people without known inflammatory conditions. Some studies suggest that the prevalence of rheumatoid factor positivity in the general population increases with age and smoking status. As a consequence, merely being rheumatoid factor positive, without any symptoms, rarely prompts follow-up aimed at early identification of rheumatoid arthritis today."

The investigators tested blood drawn from 9712 subjects in 1981 to 1983 during the Copenhagen City Heart Study for rheumatoid factor and followed the participants for over twenty-seven years. The IgM rheumatoid factor levels were correlated with the emergence of rheumatoid arthritis. The data showed a powerful correlation:

"Rheumatoid factor levels were similar from age 20 to 100 years. During 187 659 person years, 183 individuals developed rheumatoid arthritis. In healthy individuals, a doubling in levels of rheumatoid factor was associated with a 3.3-fold increased risk of developing rheumatoid arthritis, with a similar trend for most other autoimmune rheumatic diseases. The cumulative incidence of rheumatoid arthritis increased with increasing rheumatoid factor category. Multivariable adjusted hazard ratios for rheumatoid arthritis were 3.6 for rheumatoid factor levels of 25-50 IU/mL, 6.0 for 50.1-100 IU/mL, and 26 for >100 IU/mL, compared with <25 IU/mL. The highest absolute 10 year risk of rheumatoid arthritis of 32% was observed in 50-69 years old women who smoked with rheumatoid factor levels >100 IU/mL."

The authors also found associations with lupus erythematosus, systemic sclerosis, and Sjögren's syndrome. The implications are straightforward: autoimmune attack on joint and connective tissue occurs well before the condition becomes full blown. This is true for other autoimmune diseases as well. The authors conclude:

"Individuals in the general population with elevated rheumatoid factor have up to 26-fold greater long term risk of rheumatoid arthritis, and up to 32% 10 year absolute risk of rheumatoid arthritis. These novel findings may lead to revision of guidelines for early referral to a rheumatologist and early arthritis clinics based on rheumatoid factor testing."

In my practice, the Multiple Autoimmune Reactivity Screen is a valuable tool to investigate the early propensity to autoimmune attack on a range of tissues. It also helps to discriminate which active symptoms are due to autoimmunity. This study illustrates the principal that the propensity to autoimmunity can be discerned at an early stage so that measures can be taken to protect against the evolution of full-blown autoimmune disease.