It is widely accepted that the combination of arthralgia and the presence of antibodies (indicating loss of tolerance) to citrullinated proteins (ACPAs) and or IgM rheumatoid factor (RF) is appropriate to identify individuals with high risk of developing RA.1–4 Approximately 30%–40% of subjects at risk will develop RA within 1 year. The gene discussed is CD40LG; the disease is rheumatoid arthritis.