TUMOR-NECROSIS-FACTOR PROMOTER POLYMORPHISM AND SUSCEPTIBILITY TO LEPROMATOUS LEPROSY

Genetically determined differences in immune responses to environmenta l agents may underlie susceptibility to many autoimmune and infectious diseases, Leprosy provides an example of a polarity in the type of im mune response made to an infectious agent, and there is evidence that the major histocompatibility complex is genetically linked to leprosy type, It was found that HLA-DR2 is associated with both tuberculoid an d lepromatous types of leprosy; however, a variant at position -308 of the promoter of the neighboring tumor necrosis factor (TNF) gene was increased in frequency in lepromatous (odds ratio = 3.0, P = .02) but not tuberculoid leprosy, Some studies have found higher serum levels o f TNF in lepromatous than tuberculoid leprosy, and high TNF levels are found in malaria and leishmaniasis, which are also associated with th is TNF allele. It is speculated that this association reflects genetic variability in cytokine production, which influences the immune respo nse to and clinical outcome of leprosy.