Pathogenesis of nerve damage in leprosy: genetic polymorphism regulates the production of TNFα

Sarno, Euzenir Nunes; Santos, Adalberto Rezende; Jardim, Márcia Rodrigues; Suffys, Philip Noël; Almeida, Alexandre S. de; Nery, José A. C.; Vieira, Letícia; Sampaio, E. P.

doi:10.5935/0305-7518.20000087

Cited by 14 publications

(13 citation statements)

References 1 publication

(1 reference statement)

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“…88 TNF SNPs may be associated with inflammatory leprosy nerve damage, but this has not been investigated in large numbers of patients thus far. 89 More recent studies have shown that signalling deficient mutations in certain Toll like receptors (notably TLR2), which act upstream of TNF can be strongly associated with lepromatous leprosy, implicating among others, a role for TNF. 90 Malaria Strong TNF promotor SNP associations were first described in Plasmodium falciparum malaria.…”

Section: Leprosymentioning

confidence: 99%

Is there a future for TNF promoter polymorphisms?

2004

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The in vitro study of TNF promoter polymorphism (SNP) function was stimulated by the numerous case-control (association) studies of the polymorphisms in relation to human disease and the appearance of several studies claiming to show a functional role for these SNPs provided a further impetus to researchers interested in the role of TNF in their disease of interest. In this review we consider case-control studies, concentrating on the autoimmune and inflammatory diseases rheumatoid arthritis, multiple sclerosis, ankylosing spondylitis, and asthma, and on infectious diseases including malaria, hepatitis B and C infection, leprosy and sepsis/septic shock. We also review the available evidence on the functional role of the various TNF promoter polymorphisms. In general, case-control studies have produced mixed results, with little consensus in most cases on whether any TNF polymorphisms are actually associated with disease, although results have been more consistent in the case of infectious diseases, particularly malaria. Functional studies have also produced mixed results but recent work suggests that the much studied À308G/A polymorphism is not functional, while the function of other TNF polymorphisms remains controversial. Studies of the TNF region are increasingly using extended haplotypes that can better capture the variation of the MHC region.

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Section: Leprosymentioning

confidence: 99%

Is there a future for TNF promoter polymorphisms?

2004

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“…In an analysis of 57 TNF*2-positive leprosy patients, reaction responses were found much more frequently amongst heterozygotes compared to homozygotes; however, TNFa levels were similar for a small series of both TNF*1 and TNF*2 patients during and in the absence of reaction, and both sets of patients showed similar increases in TNFa levels during reaction, indicating that these polymorphisms may not influence TNFa levels in vivo. 79 It would be of interest to reassess these associations in a larger data set.…”

Section: Class III Regionmentioning

confidence: 99%

Genetics of susceptibility to leprosy

2002

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The ancient disease of leprosy can cause severe disability and disfigurement and is still a major health concern in many parts of the world. Only a subset of those individuals exposed to the pathogen will go on to develop clinical disease and there is a broad clinical spectrum amongst leprosy sufferers. The outcome of infection is in part due to host genes that influence control of the initial infection and the host's immune response to that infection. Identification of the host genes that influence host susceptibility/resistance will enable a greater understanding of disease pathogenesis. In turn, this should facilitate development of more effective therapeutics and vaccines. So far at least a dozen genes have been implicated in leprosy susceptibility and a genome-wide linkage study has lead to the identification of at least one positional candidate. These findings are reviewed here.

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“…De acordo com Santos e colaboradores 27 , em estudo envolvendo lesões de pacientes multi e paucibacilares, foi observado que a imunoexpressão do TNF-α sob a alteração da região promotora (-308G/A) da proteína era mais frequente em pacientes multibacilares. Nos estudos desenvolvidos por Sarno e colaboradores 28 , verificou-se que, em pacientes multibacilares, a alteração na produção do gene TNF nos macrófagos proporcionaria um ambiente privilegiado para a manutenção do bacilo, favorecendo a persistência da infecção.…”

Section: Sousa Jr Et Al Imunoexpressão De Tnf-α E Tgf-βunclassified

Imunoexpressão de TNF-α e TGF-β em lesões de pacientes nas diversas formas clínicas da hanseníase por meio da técnica de imunoistoquímica

et al. 2013

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Pathogenesis of nerve damage in leprosy: genetic polymorphism regulates the production of TNFα

Cited by 14 publications

References 1 publication

Is there a future for TNF promoter polymorphisms?

Is there a future for TNF promoter polymorphisms?

Genetics of susceptibility to leprosy

Imunoexpressão de TNF-α e TGF-β em lesões de pacientes nas diversas formas clínicas da hanseníase por meio da técnica de imunoistoquímica

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Pathogenesis of nerve damage in leprosy: genetic polymorphism regulates the production of TNFα

Cited by 14 publications

References 1 publication

Is there a future for TNF promoter polymorphisms?

Is there a future for TNF promoter polymorphisms?

Genetics of susceptibility to leprosy

Imunoexpressão de TNF-&#945; e TGF-&#946; em lesões de pacientes nas diversas formas clínicas da hanseníase por meio da técnica de imunoistoquímica

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Product

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Imunoexpressão de TNF-α e TGF-β em lesões de pacientes nas diversas formas clínicas da hanseníase por meio da técnica de imunoistoquímica