02674nas a2200397   4500000000100000008004100001260001300042653001200055653003800067653001100105653003800116653002000154653001100174653001200185653000900197653003900206653002600245653002800271653003200299653003200331100001400363700001500377700001500392700001500407700001600422700001300438700001500451700001600466245010500482856005900587300003100646490001300677050003200690520154000722022001402262       2000                            d  c2000 Dec10aAlleles10aEnzyme-Linked Immunosorbent Assay10aFemale10aGenetic Predisposition to Disease10aGenetic Testing10aHumans10aleprosy10aMale10aPeripheral Nervous System Diseases10aPolymorphism, Genetic10aPopulation Surveillance10aSensitivity and Specificity10aTumor Necrosis Factor-alpha1 aSarno E N1 aSantos A R1 aJardim M R1 aSuffys P N1 aAlmeida A S1 aNery J A1 aVieira L M1 aSampaio E P00aPathogenesis of nerve damage in leprosy: genetic polymorphism regulates the production of TNF alpha.  uhttp://leprev.ilsl.br/pdfs/2000/v71s1/pdf/v71s1a30.pdf  aS154-8; discussion S158-600 v71 Suppl  aInfolep Library - available3 a<p>Studies carried out over the last decade have strongly suggested that TNF alpha both overtly participates in the cell-mediated immune response against Mycobacterium leprae, and is overproduced during reaction. In addition, reactions are intimately related to the onset of nerve damage. Finally, TNF alpha has been implicated in the pathogenesis of many human and experimental autoimmune peripheral neuropathies that, as in leprosy, result in demyelination and axonal lesions. Because of recent findings associating human TNF alpha mutant alleles at the -308 position with increased production of TNF alpha in many immunological and infectious diseases, an investigation of the role of TNF2 in predisposing leprosy patients to reaction has been undertaken. Analysis of 300 patients with leprosy--210 multibacillary and 90 paucibacillary--has shown that the percentage of reactional patients was similar among both carriers and non-carriers of the TNF2 allele. However, a separate analysis of 57 carriers of TNF2 found that reactions occurred much more frequently among heterozygous than among homozygous patients. Moreover, the frequency of neuritis was somewhat greater among the heterozygous patients than among the non-carriers. Enhanced serum levels of TNF alpha have been noted in both TNF-1 and TNF-2 mutant patients in the course of leprosy reaction. Our observations to date suggest that other factors not related to the presence of the mutant gene may lead to the TNF alpha hyper-responsiveness observed during reaction.</p>  a0305-7518