RE: Researchers Find Gene Linked to MS, Arthritis

[Guest guest]

--- a <paula54@...> wrote:

> Researchers Find Gene Linked to MS, Arthritis

> Thu Apr 25,10:56 AM ET

> By E. J. Mundell

> NEW ORLEANS (Reuters Health) -

> A study in identical twins

> has uncovered a previously unknown gene with strong

> associations to both multiple sclerosis (MS) and

> rheumatoid

> arthritis

a: this is veryyy interesting...on my maternal

side my grandmother had RA....her son, my uncle has

MS...my

mom has RA.....and here I sit with

scleroderma/lupus....I hope the do follow-up posts to

this....I would love to know what the gene is...

: Thank you for your kind words...I read your

suggestion about seeing the doc when I came home from

seeing the doc...you should have been a

doctor...apparently my scleroderma is in a flare

causing severe swelling in my joints which is causing

pressure on my discs..which is causing the electric

feelings in legs and arms...what was that song about

the ankle bone connected to the...and on and on...so

after 5 years of saying NOOOOOOOOO....steroids because

everything I read says they are as bad as what ails

you I get to do Medrol for awhile....still waiting for

that Enbrel miracle drug...if anything I learning how

to wait patiently.....and learning as this stuff

progresses you

get to the point where you say ANYTHING ILL TAKE

ANYTHING....if someone had told me 10 years ago at 44

I would be putting 14 different man made chemicals

into my body.....I would have laughed them out of the

state

.....oh well enough boo-hooing....thank you again for

your kind words.....

Kathy in Il: I am sorry you are having such a time of

it....I wish we had a magic wand with your name on

it...it sounds like you have a supportive family so

that must be great..anyway my thoughts are with you..

to all the rest I hope a few less pain filled

days....Kathi in OK

>

>

__________________________________________________

[Guest guest]

Hi-

Thanks for the article- What does it mean to have a highly activated gene, or

high levels of the gene, as i think the article said? Does it mean that both

twins have that one gene, but in one twin it is activated in some way? How is

it activated? How might they test for that? thanks , bonnie L

[Guest guest]

<<.....and learning as this stuff progresses you

get to the point where you say ANYTHING ILL TAKE

ANYTHING....if someone had told me 10 years ago at 44

I would be putting 14 different man made chemicals

into my body.....I would have laughed them out of the

state>>

That's so true! I got to that point during my last flare.just make it STOP!

It frightens me how many medications I'm taking, but I'm really hoping to

get this disease under control.

Carol in FL

Re: [ ] Researchers Find Gene Linked to MS, Arthritis

--- a <paula54@...> wrote:

> Researchers Find Gene Linked to MS, Arthritis

> Thu Apr 25,10:56 AM ET

> By E. J. Mundell

> NEW ORLEANS (Reuters Health) -

> A study in identical twins

> has uncovered a previously unknown gene with strong

> associations to both multiple sclerosis (MS) and

> rheumatoid

> arthritis

a: this is veryyy interesting...on my maternal

side my grandmother had RA....her son, my uncle has

MS...my

mom has RA.....and here I sit with

scleroderma/lupus....I hope the do follow-up posts to

this....I would love to know what the gene is...

: Thank you for your kind words...I read your

suggestion about seeing the doc when I came home from

seeing the doc...you should have been a

doctor...apparently my scleroderma is in a flare

causing severe swelling in my joints which is causing

pressure on my discs..which is causing the electric

feelings in legs and arms...what was that song about

the ankle bone connected to the...and on and on...so

after 5 years of saying NOOOOOOOOO....steroids because

everything I read says they are as bad as what ails

you I get to do Medrol for awhile....still waiting for

that Enbrel miracle drug...if anything I learning how

to wait patiently.....and learning as this stuff

progresses you

get to the point where you say ANYTHING ILL TAKE

ANYTHING....if someone had told me 10 years ago at 44

I would be putting 14 different man made chemicals

into my body.....I would have laughed them out of the

state

.....oh well enough boo-hooing....thank you again for

your kind words.....

Kathy in Il: I am sorry you are having such a time of

it....I wish we had a magic wand with your name on

it...it sounds like you have a supportive family so

that must be great..anyway my thoughts are with you..

to all the rest I hope a few less pain filled

days....Kathi in OK

>

>

__________________________________________________

[Guest guest]

,

This is interesting. The first article in your message mentioned a gene

associated with MS (therefore perhaps also with MBP antibodies) " Just such a

gene turned up, and was active at a rate 8.5-times higher in the MS-affected

twin compared with the

healthy twin. " I wonder if that gene is asparagine endopeptidase ? At first

glance i got the impression that asparagine endopeptidase might be

under-expressed, it seems it is the opposite.

Jon.

--------------------------------------------------------------------------------

Endopeptidase modulated autoimmunity

Dominant myelin basic protein epitopes prevents autoimmunity and can be

hidden from T cells by the action of asparagine endopeptidase.

Myelin basic (MBP) protein can induce experimental autoimmune encephalomyelitis

(EAE) and has been implicated in the suggested autoimmune component in multiple

sclerosis. But, the mechanism by which autoreactive T cells escape tolerance

induction to MBP remains unknown. Two papers in January 14 online Nature

Immunology show that dominant MBP epitopes prevents autoimmunity and can be

hidden from T cells by the action of an asparagine endopeptidase.

Anderton and colleagues from University of Edinburgh, UK, demonstrated

that MBP contains three overlapping but distinct epitopes. They showed that only

activation of T cells specific for either of the minor MBP(89-94) or MBP(95-101)

epitopes resulted in EAE, whereas immunization with the dominant MBP(92-98)

epitope did not induce autoimmunity (Nat Immunol 2002, DOI: 10.1038/ni756).

In the second paper, Bénédicte Manoury and colleagues from University of Dundee,

UK, observed that the destructive processing by asparagine endopeptidase (AEP)

limits the presentation of the dominant MBP epitope to the T cells. They

suggested that differences in the expression of AEP could explain why some T

cells escape central tolerization in the thymus and become activated in the

central nervous system (Nat Immunol 2002, DOI: 10.1038/ni756).

In addition, Anderton et al. concluded that, " peptides must be designed to mimic

the naturally processed form of the antigen if they are to be used effectively

in therapy for autoimmune and allergic disorders " .

Tudor Toma (t.toma@...)

http://www.biomedcentral.com/news/20020114/03

--------------------------------------------------------------------------------

Researchers find gene linked to MS, arthritis

The links between different disorders seem to be growing. I have some

things that I'll post separately that discuss links between MS and

schizophrenia, arthritis and schizophrenia, MS and CFIDS, etc.

The article had links to some of the info I included below. I thought it

would be helpful to see how all these disorders overlap. Even problems with

milk proteins are mentioned in the MS info.

Researchers find gene linked to MS, arthritis

By E. J. Mundell

NEW ORLEANS, Apr 25 (Reuters Health) - A study in identical twins has

uncovered a previously unknown gene with strong associations to both

multiple sclerosis (MS) and rheumatoid arthritis, researchers report.

The finding is " just one more piece of the puzzle " in the search to find the

causes--and, it is hoped--cures for these two common, debilitating diseases,

said graduate student researcher Carolyn Greene of town University in

Washington, DC. She and her colleagues presented the findings here Wednesday

at the annual Experimental Biology 2002 meeting.

MS and rheumatoid arthritis are both autoimmune disorders, illnesses where

the body's immune system inexplicably attacks healthy tissue. In MS, immune

cells gradually wear away the protective myelin sheath surrounding nerve

fibers in the brain and spine, leading to increasing neurological and motor

impairment. In rheumatoid arthritis, tissues lining the joints become the

focus of attack, causing patients pain and disability.

Seeking to find genes linked to MS, Greene and her co-researchers conducted

detailed comparisons of the genetic make-up of a set of identical twins,

only one of whom suffered from MS. Just such a gene turned up, and was

active at a rate 8.5-times higher in the MS-affected twin compared with the

healthy twin. Greene said the gene appears to have been previously unknown,

since it " didn't match to anything " in GenBank, the human genome database.

To rule out the possibility that the finding was a fluke, the researchers

then looked for the gene in a group of healthy individuals and another group

of 13 MS patients. As expected, only the MS group had high levels of gene

activity.

The town researchers also tested individuals with other forms of

autoimmune disease for high levels of gene activity. Five patients with

rheumatoid arthritis tested all had high levels, Greene said. On the other

hand, patients with another autoimmune condition, Crohn's disease, displayed

normal levels of the gene.

Greene stressed that both MS and rheumatoid arthritis are complex diseases

likely to have both genetic and environmental causes. This discovery, she

said, was just one step on a much longer journey. The next step is to try

and determine what role the gene might play in triggering either disease.

Copyright © 2002 Reuters Limited.

WHAT IS THE MULTIPLE SCLEROSIS DISEASE PROCESS?

The Autoimmune Disease Process: General Overview

Multiple sclerosis is referred to as an autoimmune disease. The general

theory for the development of MS is that a genetically damaged immune system

is unable to distinguish between virus proteins and the body's own myelin

and so produces antibodies that attack. In other words, the body becomes

allergic to itself, a condition known as autoimmunity.

Theoretically, this condition develops when the body's immune system is

damaged by genetic or environmental factors or both, causing it to attack

its own tissues.

In the case of MS, the tissues the immune system attacks are those that make

up myelin:

Myelin is made from layers of cell membranes that are produced in the brain

and spinal cord by specialized cells called oligodendrocytes. The

destruction of this myelin sheath during the disease process is the hallmark

for multiple sclerosis.

The myelin coat is distributed in segments along the axons, the long

filaments that carry electric impulses away from a nerve cell.

The segments are separated from each other by tiny clusters called nodes of

Ranvier , which house channels for sodium ions . These sodium ions are

important for boosting the electrical charge required to pass signals from

one nerve to another.

As the myelin insulation is destroyed, signals transmitted from nerve cell

to nerve cell throughout the central nervous system are disrupted.

Experts once believed that axons themselves were spared during the disease

process. Research, however, has shown that many are severed in MS and, in

fact, axon destruction appears to start at an early stage in the disease and

may be a major cause of its irreversibility.

The body often makes corrective actions to offset the effects of the nerve

cell destruction:

For example, researches have observed an increase in the density of the

sodium channels, which carry electric charges. By increasing their numbers,

the nerve cells can continue to communicate, in spite of the loss of myelin.

The nerves also retain some capacity to remyelinate (to restore the

insulating myelin).

Such processes are probably responsible for the remissions that most MS

patients experience. Unfortunately, the disease process nearly always

eventually outpaces these corrective actions.

Onset of Multiple Sclerosis: The Autoimmune Process and the Inflammatory

Response

The Normal Immune Response.

The most important critical immune factors in the disease process are white

blood cells called lymphocytes, which consist of T-cells and B-cells. These

cells are the warriors in the immune defense system.

Receptors on T-cells acquire the ability to recognize specific molecules

called antigens. Antigens are atypically proteins from infecting organisms,

such as bacteria or viruses, and perceived as a threat to the body.

Once the antigen is identified, specific T-cells, called helper T-cells,

trigger the B-cells to release antibodies. These molecules are designed to

attach to and destroy the targeted antigen.

Autoimmunity.

Multiple sclerosis, in fact, probably all autoimmune diseases, involves an

error in the education of T-cells, which makes them unable to distinguish

self from non-self.

In multiple sclerosis, the miseducated T-cells mistake molecules in the

body's own myelin as a foreign antigen. (Such targets, then, are referred to

as self-antigens.)

In response to detection of these self-antigens, the T-cells set off the

usual cascading immune events, including the release of B-lymphocytes, to

rid the body of the perceived threat.

The B-lymphocytes fire off antibodies as usual, but in this case they are

referred to as autoantibodies, because they are attacking antigens that

belong to the body's own self.

And in MS, these self-antigens are myelin proteins, the fatty insulation

covering the nerve fibers. (Of particular interest is a substance called

myelin proteolipid protein, which comprises about half the protein in myelin

and may be a primary target for T-cells.)

To make matters worse, the process perpetuates through a cascading series of

events in which the B-cells and T-cells continue to interact, creating

numerous different self-antigens. The attacks continue and, in the process,

the original self-antigen is unrecognizable.

Cytokines and the Inflammatory Response. The inflammatory response is the

product of an overactive immune system and is a major destructive force in

an autoimmune disease.

Once the lymphocytes have launched a response to an antigen, they also

release masses of other white blood cells to gather at the injured or

infected site.

The major players in this response are white blood cells called leukocytes.

Researchers are particularly interested in leukocytes called cytokines.

These are small powerful proteins that, in tiny amounts, are indispensable

for healing. When they are overproduced, however, which occurs in MS, they

play a major role in the destructive process.

Their intensive convergence on the affected area causes it to be become

inflamed and injurious to the very cells they are designed to protect. Under

normal conditions, this inflammatory process is controlled and

self-limiting, but in people with autoimmune diseases such as multiple

sclerosis, the process persists and damage occurs in the surrounding

tissues.

Important cytokines in MS appear to be tumor necrosis factors,

interleukin-12, and interferon-gamma. (Other cytokines, including

interleukin-10 and transforming growth factor beta, may play a protective

role and help block inflammatory activity.)

Axon Destruction.

Evidence now strongly suggests that axon destruction is a major factor in

the irreversibility of MS and its progression. Microscopic studies reveal

that axons are destroyed while myelin is being peeled off. An amino acid

called N-acetylaspartate, which is critical for axonal health, undergoes

dramatic and destructive changes. Such changes appear to occur early on in

the disease process and to be ongoing. The discovery of these events

indicates that MS affects more of the brain than previously thought and is

having significant effects on research on treatments.

WHAT CAUSES MULTIPLE SCLEROSIS?

Genetic factors certainly play a role in MS. No single gene, however, is

likely to be responsible for causing MS or other autoimmune conditions.

Rather, a combination of genetic factors makes some people more susceptible

to this disease. In addition, some chemical or infection or other

environmental assault is most likely needed to trigger the autoimmune

response.

Genetic Factors

The identical twin of a patient with MS has a 30% chance of developing the

disease. First degree relatives of MS patients have a risk 20 to 50 times

higher than that of the normal population. (It should be noted that these

relatives have an overall risk that is still less than 5%.) One study found

a significant association between siblings with MS and the specific form of

the disease, either relapsing-remitting or chronic progressive, but found no

association with the age of onset or severity of initial symptoms.

Research, in fact, is leading to the conclusion that all autoimmune diseases

are basically due to the same genetic error. A 2001 study found, for

example, that the T-cell immune factors in type 1 diabetes target the same

self-antigens as in multiple sclerosis (MS). And both diseases have been

associated with cow's milk protein. Many questions are unanswered, however.

It is not known why the diseases develop in different locations to cause

separate disorders. Nor, why some autoimmune events occur in everyone but

not everyone develops an autoimmune disease.

Infectious Agents

Infectious agents, most likely viruses, are the top suspects for triggering

the autoimmune response in people genetically susceptible to MS. There are a

number of reasons for this belief:

The geographical distribution of the disease. The number of MS cases

increases the further one gets from the equator in either direction.

Multiple sclerosis clusters. Four separate clusters of multiple sclerosis

outbreaks occurred between 1943 and 1989 in the Faroe Islands, located

between Iceland and Scandinavia. During World War II, this region was

occupied by British troops. The incidence of MS increased each year for 20

years after the war, leading some researchers to think that the troops might

have brought with them some disease-causing agent.

Viral similarity to myelin. Some viruses are strikingly similar to the

myelin protein and may therefore cause confusion in the immune system,

causing the T- cells to continue to attack their own protein rather than the

viral antigen. More than one antigen may be involved, some may trigger the

disease, and others may keep the process going.

Infectious Agents Under Suspicion. Although many infectious microorganisms

have been investigated, no one agent has emerged as a proven trigger. It is

possible different MS patients may be affected by different organisms, and

that infections cause some, ,but not all, cases of MS. Organisms that are at

the top of suspect list are those that can affect the central nervous

system. The following are two primary suspects:

Herpesviruses. HHV-6, a form of herpesvirus that causes roseola, a benign

disease in children, is also known to cause encephalitis (brain

inflammation) in patients with impaired immune systems. A number of studies

have reported higher than normal rates of HHV-6 infection in MS patients and

some experts believe that may be important in MS. Other experts argue,

however, that nearly everyone harbors this virus and there is still no

evidence of a causal relationship. Other herpesviruses can also infect brain

cells. They include herpes simplex 1 and 2 (the causes of oral and genital

herpes), varicella-zoster virus (the cause of chicken pox and shingles), and

cytomegalovirus.

Chlamydia Pneumoniae. Chlamydia pneumoniae, an atypical bacterium that has

been associated with persistent inflammation in small vessels. A few studies

have reported significantly higher rates of previous Chlamydia infection in

MS patients than in individuals without MS. An important group of 2000

studies, however, reported no connection at all between Chlamydia and MS.

Some investigators suggest that different laboratory standards in

identifying the organism have produced varying results. Many experts now

believe there is no strong evidence linking the microbe to MS.

Other viruses that have been investigated include Epstein-Barr virus (the

cause of mononucleosis), measles virus, adenovirus, polyomavirus, and the

retroviruses (HIV, HTLV-I, and HTLV-II).

Vaccinations. Concerns about a link between the hepatitis B vaccine and MS

led France to halt a major vaccination program in 1998. Subsequent research

published in 2001, however, found no evidence of any causal association.

Research also ruled out a link between any other vaccinations, such as or

influenza, and relapses of MS.

Other Possible Triggers

Trauma. Some experts believe that injury (trauma) to the head, neck, or

upper back may trigger new or recurrent symptoms by disrupting the

blood-brain barrier and allowing immunological attacks on the brain. This is

a highly controversial theory, however, with very little supporting

evidence.

Stress. There is a significant correlation between chronic, long-term stress

and exacerbation of MS symptoms. (Stress is not a cause of MS, however.)

Cow's Milk during Early Infancy. Breast milk contains factors that may help

regulate the immune response, and there is some evidence that infants fed

only on cow's milk may have a higher risk for either diabetes type 1 or

multiple sclerosis later in life. Studies on national differences in

diabetes suggest that the risk may vary with different milk proteins,

suggesting that not all cow's milk is the same and some proteins carry

higher risks than others.

WHO GETS MULTIPLE SCLEROSIS?

Between 250,000 and 350,000 Americans and about 1.1 million people worldwide

have multiple sclerosis, and the incidence appears to be increasing. Risk

factors include the following:

Age. Onset typically occurs between the ages of 15 and 40 years, with a peak

incidence between 20 and 30 years old.

Gender. Women are affected twice as often as men are.

Ethnicity. Multiple sclerosis occurs worldwide but is most common in

Caucasian people of northern European origin, especially those of ish

descent. It is extremely rare among Asians and Africans.

Geography. In general, MS is more prevalent in temperate regions of the

world than in the tropics. Multiple sclerosis affects about one in every

1000 people in Western nations. Specifically, prevalence is highest in

northern Europe, southern Australia, and the middle regions of North

America. The incidence has been increasing in southern Europe. It is unclear

whether this pattern is attributable to environmental factors or to

genetics.

Family History. A family history of the disease also puts people at risk,

although the risk for someone inheriting all the genetic factors

contributing to MS is only about 2% to 4%.

--------------------------------------------------------------------------------\

----------------------------------------------------------------

WHAT CAUSES RHEUMATOID ARTHRITIS?

Rheumatoid arthritis is unlikely to be due to a single cause, but rather a

combination of genetic and environmental factors that trigger an abnormal

immune response.

The Inflammatory Process

The inflammatory process is a byproduct of the body's immune system, which

fights infection and heals wounds and injuries. When an injury or an

infection occurs, white blood cells are mobilized to rid the body of any

foreign proteins, such as a virus. The masses of blood cells that gather at

the injured or infected site cause the area to become inflamed. Under normal

conditions, the inflammatory process is controlled and self-limited, but in

people with chronic rheumatoid arthritis, certain defects, probably genetic,

keep this process going.

The primary infection-fighting units are two types of white blood cells,

lymphocytes and leukocytes. Lymphocytes include two subtypes known as

T-cells and B-cells. Normally, when a foreign agent infects the body, helper

T-cells recognize that the invader, known as an antigen, is an alien so it

triggers a series of immune responses to destroy the imposter. In rheumatoid

arthritis, however, a process called autoimmunity occurs. The T-cells

mistake the body's own collagen cells as foreign antigens and set off a

series of events to rid the body of the perceived threat. Initial events

include stimulation of lymphocyte B-cells to produce antibodies, molecules

designed for attack on a specific antigen. When these antibodies attack the

body's own tissue, they are called autoantibodies.

The leukocytes are the other major white blood cells that are spurred into

action by the overactive T-cells. Leukocytes stimulate the production of two

key players in the inflammatory process: leukotrienes, which attract even

more white blood cells to the area, and prostaglandins, which open blood

vessels and increase blood flow. As part of their activity, leukocytes also

produce cytokines , small proteins that many researchers believe are

critical in the process that leads to joint damage and may even be

responsible for inflammation that occurs in parts of the body beyond the

joints. In small amounts, these powerful chemicals are indispensable for

healing. If overproduced, however, cytokines can cause serious damage,

including fever, shock, and even damage to organs, such as the liver.

Important cytokines in the process of rheumatoid arthritis are those known

as tumor necrosis factor and interleukins. Some cytokines play a role in

releasing enzymes, such as those known as collagenase and cathepsin L, which

destroy collagen.

One of the most important cytokines currently targeted in rheumatoid

arthritis research is tumor necrosis factor (TNF); levels of this cytokine

soar in the synovial fluid during arthritic flare-ups. TNF's inflammatory

effects implicate it in many autoimmune disorders including multiple

sclerosis, Crohn's disease, psoriasis, psoriatic arthritis, and others.

Other cytokines under study are interferon, GM-CSF, and interleukins 1,6, 9,

10, 11, 15, and 17. Excessive amounts of nitric oxide, a substance important

in blood vessel flexibility and dilation, may also play a major destructive

role in RA.

Genetic Factors

Although much has been learned about the inflammatory process leading to

rheumatoid arthritis, researchers have yet to uncover the factors that lead

to this devastating self-attack. One prevalent theory is that a combination

of factors trigger rheumatoid arthritis, including genetic susceptibility,

an abnormal autoimmune response, and a viral infection.

HLA-DR4. HLA is a genetically determined element of the immune system that

includes molecules that trap antigens, which are then targeted and attacked

by the immune system. Researchers have identified a molecule called HLA-DR4,

which is present in many patients with autoimmune conditions. In people who

have this genetic susceptibility, the immune system may be tricked into

attacking collagen protein because of its resemblance to some actual foreign

antigen, such as a virus. HLA-DR4, however, is also present in many people

who do not contract RA, and many experts believe that more than one gene

must be involved in order for the disease to develop.

Lack of Corticotropin-Releasing Hormone. Some people may have a genetic

deficiency of a hormone known as corticotropin-releasing hormone (CRH),

which produces corticosteroids, other hormones that suppress the

inflammatory process.

P53. Even successful treatment of the inflammation does not completely

prevent further joint destruction. Research has found the presence of a

mutated gene known as p53 in synovial tissue obtained from a group of

patients. In such cases, the mutation is not inherited but appears to

develop as part of the disease process. In its normal state, the p53 gene is

known as a tumor suppressor gene and causes apoptosis, a natural process by

which cells self-destruct. When the p53 gene is defective, cells do not die

but continue to reproduce; such actions may help explain the development of

a pannus, a growth that occurs in RA composed of thickened synovial tissue,

and the further destruction of cartilage and bone even after the

inflammation has been treated. A p53 mutation is found in many cancers. In

RA, although the defective p53 gene behaves differently, the risk for

certain cancers is higher than normal in patients with rheumatoid arthritis.

It is not known, however, whether the p53 has any role in this increased

risk.

LMP-1. The anti-arthritis gene LMP-1, identified in 1999, affects

interleukin-1, an immune factor that plays an important role in joint

damage.

Infectious Triggers

Although many bacteria and viruses have been studied, no single organism has

been proven to be the primary trigger for the autoimmune response and

subsequent damaging inflammation. Higher than average levels of antibodies

that react with the common intestinal bacteria E. coli have appeared in the

synovial fluid of people with RA, which some experts think may stimulate the

immune system to perpetuate RA once the disease has been triggered by some

other initial infection.

Hormonal Triggers. Hormonal imbalances may contribute to the processes

leading to RA. People with RA appear to have lower than normal levels of

certain hormones secreted by the adrenal gland, including cortical, a stress

hormone, and, in women, dehydroepiandrosterone (DHEA), a weak androgen (male

hormone).

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[Guest guest]

I wish they had given info on the gene. I'm assuming it would be activation

due to some type of stressor, exposure, etc. It could be an immune related

gene that activates due to some type of antigen, an enzyme that activates to

metabolize something, or???

It could also be a gene that has no positive effect or purpose, but becomes

activated by other genes or processes. All I can really do is guess without

more information.

If it turns out that they have discovered a " NEW " or unknown gene,

eventually it could be tested for. It would be the same type of thing they

do now with disorders that run in families. Some people decide to have

tests run to see if they are carrying the gene that makes them susceptable.

It doesn't mean that they will definitely develop the disease. Other

factors play a role in whether that happens.

Cheryl

>From: bonniedanphil@...

>Reply-

>

>Subject: Re: Researchers find gene linked to MS, arthritis

>Date: Fri, 26 Apr 2002 09:39:08 EDT

>

>Hi-

>Thanks for the article- What does it mean to have a highly activated gene,

>or

>high levels of the gene, as i think the article said? Does it mean that

>both

>twins have that one gene, but in one twin it is activated in some way? How

>is

>it activated? How might they test for that? thanks , bonnie L

>

>

>

[Guest guest]

Kathi,

I'll be watching for an update. Don't get upset about the Medrol pack. They

are a lifesaver when going through a flare. Long term steroids are the ones

with the side effects, so if you're able to stay off of long term, you're in

great

shape. Many people have no choice. I feel the same way you do about all

the meds. We all do, but what choice is there? We just have to keep the faith

that something better is on the horizon.

hugs,

a

Re: [ ] Researchers Find Gene Linked to MS, Arthritis

--- a <paula54@...> wrote:

> Researchers Find Gene Linked to MS, Arthritis

> Thu Apr 25,10:56 AM ET

> By E. J. Mundell

> NEW ORLEANS (Reuters Health) -

> A study in identical twins

> has uncovered a previously unknown gene with strong

> associations to both multiple sclerosis (MS) and

> rheumatoid

> arthritis

a: this is veryyy interesting...on my maternal

side my grandmother had RA....her son, my uncle has

MS...my

mom has RA.....and here I sit with

scleroderma/lupus....I hope the do follow-up posts to

this....I would love to know what the gene is...

: Thank you for your kind words...I read your

suggestion about seeing the doc when I came home from

seeing the doc...you should have been a

doctor...apparently my scleroderma is in a flare

causing severe swelling in my joints which is causing

pressure on my discs..which is causing the electric

feelings in legs and arms...what was that song about

the ankle bone connected to the...and on and on...so

after 5 years of saying NOOOOOOOOO....steroids because

everything I read says they are as bad as what ails

you I get to do Medrol for awhile....still waiting for

that Enbrel miracle drug...if anything I learning how

to wait patiently.....and learning as this stuff

progresses you

get to the point where you say ANYTHING ILL TAKE

ANYTHING....if someone had told me 10 years ago at 44

I would be putting 14 different man made chemicals

into my body.....I would have laughed them out of the

state

....oh well enough boo-hooing....thank you again for

your kind words.....

Kathy in Il: I am sorry you are having such a time of

it....I wish we had a magic wand with your name on

it...it sounds like you have a supportive family so

that must be great..anyway my thoughts are with you..

to all the rest I hope a few less pain filled

days....Kathi in OK

>

>

__________________________________________________

[Guest guest]

I'm assuming that you mean't Cheryl <grin>

I would assume that this is not the gene they referred to. According to the

article they couldn't find a gene that matched.

" " Greene said the gene appears to have been previously unknown,

since it " didn't match to anything " in GenBank, the human genome database. " "

Peptidase_C13, Peptidase C13 family. This family of peptidases is known as

the hemoglobinase family because it contains a globin degrading enzyme from

blood parasites. However relatives are found in plants and other organisms

that have other functions. Members of this family are asparaginyl peptidases

Cytogenet Cell Genet 1996;74(1-2):120-3 Related Articles, Nucleotide, OMIM,

Protein, Books, LinkOut

Molecular cloning of a human cDNA encoding putative cysteine protease

(PRSC1) and its chromosome assignment to 14q32.1.

Tanaka T, Inazawa J, Nakamura Y.

Laboratory of Molecular Medicine, University of Tokyo, Japan.

We have isolated a novel human cDNA encoding a protein of 433 amino acids

which shows 40% sequence identity to a hemoglobinase of Schistosoma

japonicum, one of the cysteine proteases in the pathway by which trematodes

degrade host-cell globin. It also has 36% identity to a cysteine protease of

the soybean Glycine max that processes proproteins of various vacuolar

proteins into mature form after translation. Considering the sequence

similarities among these proteins in such widely divergent species, the

human cDNA reported here appears to represent one of a group of genes that

have been well conserved during evolution. Northern-blot analysis revealed

the strongest expression of this gene in kidney, among the human tissues

examined. By fluorescence in situ hybridization, we determined its

chromosome location at 14q32.1.

PMID: 8893817 [PubMed - indexed for MEDLINE]

>From: " Jon " <jerseybean@...>

>Reply-

>< >

>Subject: Re: Researchers find gene linked to MS, arthritis

>Date: Sat, 27 Apr 2002 00:10:04 +0100

>

>,

>

>This is interesting. The first article in your message mentioned a gene

>associated with MS (therefore perhaps also with MBP antibodies) " Just such

>a gene turned up, and was active at a rate 8.5-times higher in the

>MS-affected twin compared with the

>healthy twin. " I wonder if that gene is asparagine endopeptidase ? At

>first glance i got the impression that asparagine endopeptidase might be

>under-expressed, it seems it is the opposite.

>

>Jon.

>

>

>-------------------------------------------------------------------------------\

-

>

>

> Endopeptidase modulated autoimmunity

> Dominant myelin basic protein epitopes prevents autoimmunity and can

>be hidden from T cells by the action of asparagine endopeptidase.

>

>

>Myelin basic (MBP) protein can induce experimental autoimmune

>encephalomyelitis (EAE) and has been implicated in the suggested autoimmune

>component in multiple sclerosis. But, the mechanism by which autoreactive T

>cells escape tolerance induction to MBP remains unknown. Two papers in

>January 14 online Nature Immunology show that dominant MBP epitopes

>prevents autoimmunity and can be hidden from T cells by the action of an

>asparagine endopeptidase.

>

> Anderton and colleagues from University of Edinburgh, UK,

>demonstrated that MBP contains three overlapping but distinct epitopes.

>They showed that only activation of T cells specific for either of the

>minor MBP(89-94) or MBP(95-101) epitopes resulted in EAE, whereas

>immunization with the dominant MBP(92-98) epitope did not induce

>autoimmunity (Nat Immunol 2002, DOI: 10.1038/ni756).

>

>In the second paper, Bénédicte Manoury and colleagues from University of

>Dundee, UK, observed that the destructive processing by asparagine

>endopeptidase (AEP) limits the presentation of the dominant MBP epitope to

>the T cells. They suggested that differences in the expression of AEP could

>explain why some T cells escape central tolerization in the thymus and

>become activated in the central nervous system (Nat Immunol 2002, DOI:

>10.1038/ni756).

>

>In addition, Anderton et al. concluded that, " peptides must be designed to

>mimic the naturally processed form of the antigen if they are to be used

>effectively in therapy for autoimmune and allergic disorders " .

>

>Tudor Toma (t.toma@...)

>

>http://www.biomedcentral.com/news/20020114/03

>

>

_________________________________________________________________

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[Guest guest]

Thanks Cheryl,

Sorry for muddling up your name and taking so long about getting back to you.

You do have a valid point, though I don't think you have demonstrated that the

asparagine endopeptidase detected is actually the cysteine protease from a

family of peptidases is known as the hemoglobinase family, even though they

state: " members of this family are asparaginyl peptidases " . The

hemoglobinase/cysteine protease located at 14q32.1. in the abstract you posted

[published (1996) prior to the study I was discussing (2002)] suggests that had

asparagine endopeptidase been the gene that " was active at a rate 8.5-times

higher in the MS-affected twin " they most probably would have picked it up,

(though we still don't know the gene designation they refer to in that article).

I'm not saying you are wrong, but I am saying there is a possibility that the

hemoglobinase/cysteine proteases from 14q32 might not actually be the asparagine

endopeptidase, there quite possibly are others.

I have just asked some questions of a MS researcher and if I get anywhere I will

let you know. I also will try to find out more about the gene that " was active

at a rate 8.5-times higher " . I don't expect they will say it is 14q32 but it

will be interesting to see if there is any association with other members of

this family.

Jon.

Re: Researchers find gene linked to MS, arthritis

>Date: Sat, 27 Apr 2002 00:10:04 +0100

>

>,

>

>This is interesting. The first article in your message mentioned a gene

>associated with MS (therefore perhaps also with MBP antibodies) " Just such

>a gene turned up, and was active at a rate 8.5-times higher in the

>MS-affected twin compared with the

>healthy twin. " I wonder if that gene is asparagine endopeptidase ? At

>first glance i got the impression that asparagine endopeptidase might be

>under-expressed, it seems it is the opposite.

>

>Jon.

>

>

>-------------------------------------------------------------------------------\

-

>

>

> Endopeptidase modulated autoimmunity

> Dominant myelin basic protein epitopes prevents autoimmunity and can

>be hidden from T cells by the action of asparagine endopeptidase.

>

>

>Myelin basic (MBP) protein can induce experimental autoimmune

>encephalomyelitis (EAE) and has been implicated in the suggested autoimmune

>component in multiple sclerosis. But, the mechanism by which autoreactive T

>cells escape tolerance induction to MBP remains unknown. Two papers in

>January 14 online Nature Immunology show that dominant MBP epitopes

>prevents autoimmunity and can be hidden from T cells by the action of an

>asparagine endopeptidase.

>

> Anderton and colleagues from University of Edinburgh, UK,

>demonstrated that MBP contains three overlapping but distinct epitopes.

>They showed that only activation of T cells specific for either of the

>minor MBP(89-94) or MBP(95-101) epitopes resulted in EAE, whereas

>immunization with the dominant MBP(92-98) epitope did not induce

>autoimmunity (Nat Immunol 2002, DOI: 10.1038/ni756).

>

>In the second paper, Bénédicte Manoury and colleagues from University of

>Dundee, UK, observed that the destructive processing by asparagine

>endopeptidase (AEP) limits the presentation of the dominant MBP epitope to

>the T cells. They suggested that differences in the expression of AEP could

>explain why some T cells escape central tolerization in the thymus and

>become activated in the central nervous system (Nat Immunol 2002, DOI:

>10.1038/ni756).

>

>In addition, Anderton et al. concluded that, " peptides must be designed to

>mimic the naturally processed form of the antigen if they are to be used

>effectively in therapy for autoimmune and allergic disorders " .

>

>Tudor Toma (t.toma@...)

>

>http://www.biomedcentral.com/news/20020114/03

>

>

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