CMT and the autoimmune system/workshop report/1B

[Guest guest]

(Note: Dr. Vinci sent this to me a few days ago for posting to ALL the

group - for those of you that have just joined , Dr. Paolo

Vinci is a leading CMT Rehabilitation Management Specialist in Italy, a

member of this group, and he has has CMT since childhood. His book is

listed in our 'bookmarks' should you wish more CMT information) ~ G

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-

(From Paolo) I too have read the book chapter quoted by Ruth Warren

about immune system and CMT and also met the author at the 3rd Int.

Conference in Canada. Unfortunately I have not read the articles quoted

in the references.

However I do not think that so many CMT people (one third, according to

) have immune deficits: I have visited more than 300 CMTers and

nobody told me that they needed maintenance or repeated antibiotic

therapy to control persistent skin infections, as suggested by .

3 years ago I attended a Workshop organized by the European CMT

Consortium: one of the topics was " Immune system and epigenetic factors

as modulators of pathology " .

This is the text published on Neuromuscular Disorders:

Immune system and epigenetic factors as modulators of pathology.

Angelo Schenone (Genova, Italy) reviewed data from the literature that

showed clinical and histopathological evidence for an involvement of the

immune system in the

pathogenesis of inherited neuropathies. Christoph Schmid and Rudolf

i (Wurzburg,

Germany) presented data from a possible impact of immune cells in

heterozygous P0 mice, a model for CMT1B.

Cross breeding of these mice with immune-deficient mouse mutants (e.g.

RAG-1 mice) resulted in a significant amelioration of the pathological

phenotype as revealed

by electron microscopic and electrophysiological investigations. The

observation that isolated splenocytes from P0 mice show a stronger

proliferation rate than splenocytes

from wild type mice when exposed to myelin components, might reflect

that chronic, genetically mediated myelin degeneration in the mutants

might elicit autoimmunity.

Ralf Gold (Wurzburg, Germany) summarised the principle mechanisms

underlying the pathogenesis in acquired, inflammatory neuropathies. He

particularly focused on the action of T-lymphocytes as producers of

cytokines or of cytotoxic enzymes, such as metalloproteases, perforin

and granzyme. In addition, T-lymphocyte-mediated cyto

kine secretion can indirectly attract macrophages that can be

detrimental for neural cells by secreting cytokines, free oxygen

radicals, nitric oxide and toxic metabolites. As antigen-presenting

cells macrophages can augment the cytooxic action of T-lymphocytes. The

B-lymphocytes interact with specific T-helper cells and serve as

constituents of humoral cytotoxity. In principle, such mechanisms could

also modulate pathogenesis in inherited neuropathies.

Although clear hints for an involvement of the immune system are rarely

found in the clinics and there might be also more coincidental than

causative links between inherited neuropathies and inflammatory

diseases, it appears plausible to assume that the immune system could

act as a modulating factor during the progression of the disease. The

involvement of immune mechanisms might provide one explanation for the

response of some reported patients on immunomodulatory drugs and

possibly also for the high variability in the severity of inherited

neuropathies even within one and the same family.

[Guest guest]

-Can you give me any information on Ruth Warren. Is she quoted in

Dr. Vinci's book or is it somewhere else? I am interested in any

references to CMT and the immune system. If anyone has any, please

post them. Thanks.

Amelia

(From Paolo) I too have read the book chapter quoted by Ruth Warren

about immune system and CMT and also met the author at the 3rd Int.

Conference in Canada. Unfortunately I have not read the articles

quoted in the references.

However I do not think that so many CMT people (one third,

according to ) have immune deficits: I have visited more than 300 CMTers

and nobody told me that they needed maintenance or repeated antibiotic

therapy to control persistent skin infections, as suggested by

.

3 years ago I attended a Workshop organized by the European CMT

Consortium: one of the topics was " Immune system and epigenetic

factors as modulators of pathology " .

This is the text published on Neuromuscular Disorders:

Immune system and epigenetic factors as modulators of pathology.

Angelo Schenone (Genova, Italy) reviewed data from the literature

that showed clinical and histopathological evidence for an involvement

of the immune system in the pathogenesis of inherited neuropathies. Christoph

Schmid and Rudolf

i (Wurzburg, Germany) presented data from a possible impact of immune

cells in

heterozygous P0 mice, a model for CMT1B.

Cross breeding of these mice with immune-deficient mouse mutants

(e.g.

RAG-1 mice) resulted in a significant amelioration of the

pathological phenotype as revealed by electron microscopic and

electrophysiological investigations. The

observation that isolated splenocytes from P0 mice show a stronger

proliferation rate than splenocytes from wild type mice when exposed to myelin

components, might reflect

that chronic, genetically mediated myelin degeneration in the

mutants might elicit autoimmunity.

Ralf Gold (Wurzburg, Germany) summarised the principle mechanisms

underlying the pathogenesis in acquired, inflammatory neuropathies.

He particularly focused on the action of T-lymphocytes as producers of

cytokines or of cytotoxic enzymes, such as metalloproteases,

perforin and granzyme. In addition, T-lymphocyte-mediated cyto

kine secretion can indirectly attract macrophages that can be

detrimental for neural cells by secreting cytokines, free oxygen

radicals, nitric oxide and toxic metabolites. As antigen-presenting

cells macrophages can augment the cytooxic action of T-lymphocytes.

The B-lymphocytes interact with specific T-helper cells and serve as

constituents of humoral cytotoxity. In principle, such mechanisms

could also modulate pathogenesis in inherited neuropathies.

Although clear hints for an involvement of the immune system are

rarely found in the clinics and there might be also more coincidental than

causative links between inherited neuropathies and inflammatory

diseases, it appears plausible to assume that the immune system

could act as a modulating factor during the progression of the disease.

The involvement of immune mechanisms might provide one explanation for

the response of some reported patients on immunomodulatory drugs and

possibly also for the high variability in the severity of inherited

neuropathies even within one and the same family.