Genes gone awry

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Genes gone awry

Postby TwistedHelix » Mon Sep 10, 2007 5:10 am

I've run this through my patented, " Gobbledygook – to – English", translating machine and it would appear that, during a relapse, a number of genes are expressed which prevent the white blood cells from killing themselves at the correct time. This would mean that immune system activity, which might start out as just a normal bit of housekeeping, goes on for far too long and leads to damage:


Impaired expression of peripheral blood apoptotic-related gene transcripts in acute multiple sclerosis relapse.
Ann N Y Acad Sci. 2007 Jun;1107:155-67
Authors: Achiron A, Feldman A, Mandel M, Gurevich M
Differential expression of apoptotic genes may influence the susceptibility of activated lymphocytes to expand and induce acute relapse and persistent inflammation in patients with relapsing-remitting multiple sclerosis (RRMS). The exact relationship between alterations in apoptotic-related gene expression and clinical disease activity has not been broadly evaluated. In this study we studied peripheral blood mononuclear cells (PBMCs) expression of pro- and antiapoptotic genes in RRMS patients during acute relapse in comparison to patients in remission. Using cDNA Affymetrix microarrays platform (U133A2 microarrays) we analyzed the gene expression profile of PBMC derived from 22 RRMS patients in acute relapse (15 females, mean age 34.6 +/- 1.8 years, disease duration 5.6 +/- 0.8 years) in comparison to 20 sex- and age-matched RRMS patients in remission. One thousand five hundred seventy-eight gene transcripts significantly differentiated acute multiple sclerosis (MS) relapse from remission. This characteristic gene expression signature was enriched by an apoptotic-related pathway. The 1578 gene transcripts that significantly differentiated acute relapse from remission were enriched by 55 apoptotic-related genes in that reflected different operating pathways during the acute phase of the disease. These genes mainly involved the caspase-dependent pathway and included overexpression of the negative regulator of FAS-induced apoptosis (TOSO) and the BCL2 antiapoptotic family members (BCL2, BCL2 AA) as well as downexpression of proapoptotic genes like BAX, apoptotic protease-activating factor 1 (APAF1) and caspases 1, 2, 8, 9. and 10. An additional group of antiapoptotic genes related to T cell receptor-mediated apoptosis was also found to be overexpressed in acute relapse and included TCR-binding CD3E antigen, antiapoptotic serine threonin kinase (AKT), and NF kappa B-associated genes like reticuloendotheliosis viral oncogene homolog A (RELA) and human T cell leukemia virus type I-binding protein (Tax1BP) known to inhibit tumor necrosis factor (TNF)-induced apoptosis. Our findings demonstrate impaired apoptotic mechanisms in peripheral lymphocytes from RRMS patients during acute relapse. This suggests that the inflammatory process in active disease is targeted by inhibition of proapoptotic and repression of antiapoptotic genes that allow prolonged abnormal immune responses.
PMID: 17804543 [PubMed - in process]
Dom
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Postby bromley » Mon Sep 10, 2007 8:55 am

Dom,

Good find. It fits it with an answer given by Dr Alasdair Coles to a question I posed at an "ask the expert " session.

Ian


I am not sure I can answer your question directly….. certainly I am not sure we can contribute anything to the debate about infective triggers.

But we have made some observations that are relevant. For instance, we –as others - have noted that the immune cells from people with multiple sclerosis do not die as quickly as they should (by a programmed suicide system called “apoptosis”). This is important because one way of stopping an immune attack is for the immune cells themselves to die. And we know that all people (with or without multiple sclerosis) have immune cells that react against myelin. Perhaps getting multiple sclerosis is simply down to a defect in the mechanism that causes immune cells to die off…..

If so, one way of treating multiple sclerosis might be to restore the mechanism of apoptosis. We have some information on this, but it is too early to go public on an open website!
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