Lupus (Systemic Lupus Erythematosus)-Cause The exact cause of lupus is not known. Experts believe that some people are born with certain genes that affect how the immune system works. These people are more likely to get lupus. Then a number of other things can trigger lupus attacks. These include certain medicines, certain chemicals, tobacco smoke, certain infections, and sunlight. Although these things can trigger lupus, they may affect one person but not another person.