Specifically, while we do not yet know the complete pathophysiologic processes that may drive RF generation in pre-RA, ACPA and dual RF-IgA and RF-IgM positivity is likely indicative of an expansion of autoimmune processes towards a state where initiation of synovitis may be more likely and more imminent (4, 31). The gene discussed is CD40LG; the disease is rheumatoid arthritis.