Research: blockade of TNF can trigger the onset of MS

Objective. To determine the pattern of demyelinating disorders (DDs)
occurring during anti-TNF-α therapy.

Methods. Between June 2005 and April
2008, 1800 French rheumatologists and internists were contacted to
report cases of DDs occurring in patients treated with

Results. After a median of 10.2 (1.5-39.9) months of
treatment, 33 patients developed DDs: 22 had CNS and 11 peripheral
nervous system (PNS) involvement. Underlying diseases were RA (n = 16),
AS (n = 11), PsA (n = 4), JIA (n = 1) and PM (n = 1). Anti-TNF-α was
infliximab (n = 15), etanercept (n = 12) or adalimumab (n = 6). CNS
involvement was encephalic lesions (n = 16), transverse myelitis (n = 8)
or retrobulbar optic neuritis (n = 5). Cerebrospinal fluid (CSF)
analysis in 16 patients and MRI in 20 patients were abnormal. All
patients discontinued anti-TNF-α. Fifteen patients required steroids.
Twenty patients initially improved. Five patients developed multiple sclerosis.
PNS involvement was chronic (n = 9) or acute inflammatory demyelinating
polyneuropathy (n = 2). CSF analysis revealed an increased protein
level in nine patients. Nerve conduction studies confirmed DD in all
these patients. Anti-TNF-α was discontinued in 10 patients and 8
received i.v. immunoglobulins. Two patients relapsed after introduction
of another anti-TNF-α. Overall, a causal relationship between anti-TNF-α
and DD was considered as probable in 31 patients and definite in 2 who
had positive rechallenge.

Conclusion. Causal relationship between
anti-TNF-α and induction of DD remains unclear, but in some cases the
chronology of clinical events is suggestive. Nevertheless, DD might
persist despite treatment discontinuation, suggesting that anti-TNF-α
could trigger the demyelinating process, which further evolves

People treated
with Lemtrada can develop autoimmune thyroid disease, it appears that
people with arthritis treated with anti-tumour necrosis
factor develop demyelinating disease and multiple sclerosis. This is
further evidence that overall blockade of TNF is not a good idea in MS.
Most experimental data may suggest that TNF blockade could be good,
however I think this shows that TNF does lots of different things some could be good and others bad and balance is that its removal at least from the peripheral compartment is bad news.
This can tell us something about biology. Following Lemtrda
administration there is a cytokine storm, quelled by steroids, that
reactive old demylinated lesions

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  • A little bit different view:
    Description of my possible medical history with the following approach:

    – YE leads to an infection of the Peyer's patches, the liver and the spleen

    – In immunocompromised patients, it may also come to the dissemination of the infection with neurological involvement

    – Yersinia can suppress the immune cascade active. Intracellular bacterial survival is prolonged periods

    – The neighborhood of fluid spaces with eg an osmotic gradient from the infected tissue to fluid ensure the transport of substances immunologically active, which could trigger an immune response. These substances are dissolved in a different place from the liquid (ie. CSF) where they are presented to the immune system. If this substance as the cause is not known, the image of an autoimmune disease is presented.
    A: autoimmune disease.

    – The problem is that the place of the immune presentation is not related with the place of "immune production". So the actual infection can not be effectively combated by a directed immune response. This raises a picture of a B: a chronic disease.

    – If the host cell or the intracellular bacteria is died, active suppression of the signal cascade is impossible. Immune processes directed (possibly after sufficient time for learning) and effective start against the infection. It caused tissue damage at the site of infection, especially when infected cells become immune-presenting cells. There is a heavy
    C: disease flare, stays until the end of the presentation of immunological trigger.

    – The different D: courses of progression are then depending on how many yersinia-bacteria have been destroyed in a disease flare, and how many survived (because still hidden in other cells) or had returned to other cells can escape. Also it plays a role in how many yersinia had been able to escape the phagocytosis. This is another weapon of yersinia, which helps to lead to a E: Chronic infection.

    – Long persistence by low propagation and growth speed: The rapid intracellular replication would increase the risk of an early immune response. Sometimes less is more effective.

    – The longer the duration of the intracellular infection is, without the immune scored note of the infection, the more of neighboring cells can be infected cells, proceed by transcytosis. The period until the first strong immune response determines the degree of dissemination of the infection. The later the directed immune response came up, the heavier F: the expected course will be, because the likelihood that infected tissue could become involved with in immune processes is increased.

    – Geographical Distribution: The possibility of cold enrichment of Yersinia is an advantage for YE compared to other bacteria. It seems possible that the G: spread of Yersinia and the MS have similar priorities, apart from the white patches from the different cards.

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