The appearance of RF of the immunoglobulin M (IgM) isotype years before the onset of disease was first reported by Aho and colleagues [4] and has been confirmed in a number of studies showing that RF of the IgM isotype, as well as the immunoglobulin G (IgG) and immunoglobulin A (IgA) isotypes, preceded the onset of RA [4–7]. The gene discussed is CD40LG; the disease is rheumatoid arthritis.