Autoantibodies can antecede overt clinical disease by years, as demonstrated by the fact that serological positivity for anti-SSA/Ro autoantibodies can be detected long before clinical symptoms of Systemic Lupus Erythematosus (SLE);1 however, autoantibody profiles alone cannot predict which patients will develop clinically significant disease versus those who will remain in a benign autoimmune state. The gene discussed is CALR; the disease is systemic lupus erythematosus.