Scientists Pinpoint Gene Behind Autoimmune Diseases

[Guest guest]

Scientists Pinpoint Gene Behind Autoimmune Diseases

'Hot

signal' on chromosome 17 could be target for therapies against lupus, other

disorders

WEDNESDAY, March 21 --

Variations in one specific gene appear to be behind several different

autoimmune and auto-inflammatory diseases.

The pinpointed region of

chromosome 17, called NALP1,

could be a new target for treatment, said the authors of a study in the March 22 issue of the New

England Journal of Medicine.

" This part of the immune

system may respond to triggers coming from the environment, like bacteria or

viruses, and there are indications that you can turn it off. So,

we're very, very hopeful that there may be drugs that allow us to do

that, " said the study's senior author, Dr. A. Spritz,

who directs the Human Medical Genetics Program at the University

of Colorado at Denver and Health

Sciences Center.

Spritz added, " That's not going to help people with childhood

diabetes, where the damage is already complete. But,

for a number of chronic autoimmune disorders, like lupus and vitiligo, if you turn off the autoimmune process, the body

could repair itself. "

Some 80 autoimmune and

auto-inflammatory disorders, which occur when the immune system malfunctions

and starts destroying normal tissue, affect between 15 million and 25 million

people in the United

States,

particularly women.

A few of the autoimmune

diseases are caused by mutations in single genes, but most appear to be more

complex. Scientists suspect that some genes may

predispose individuals to one or more diseases, whereas other genes may

predispose individuals to autoimmune and auto-inflammatory diseases in general.

" There has been a feeling

for decades that autoimmune diseases are somehow related, " said Dr.

Gregersen, author of an accompanying editorial in the

journal and director of the

S. Boas Center for Genomics and Human Genetics at the Feinstein Institute

for Medical Research in Manhasset, N.Y.

Interactions between gene

variants and environmental factors also play a role in triggering the onset of

a disease.

Spritz and his colleagues have long focused on patients with vitiligo, a disorder in which pigment cells are destroyed,

resulting in white patches on the skin and sometimes the hair.

Individuals with vitiligo tend also to have

other autoimmune and auto-inflammatory diseases, as do their relatives. But the combinations of diseases are not very consistent.

" They probably have genes

that predispose more toward autoimmunity in general and not specific

disorders, " Spritz said.

The team did a systematic

genetic analysis of 656 persons from 114 extended families in the United States and United Kingdom who had multiple autoimmune diseases, including vitiligo. This led them to a

number of genetic possibilities, but the " hottest " signal was a

region on chromosome 17, which had shown up previously as possibly harboring a

lupus gene in families who also had vitiligo.

A closer examination revealed a

collection of variations in a specific gene, NALP1.

" We don't really know

which one causes the disease, but we can use the variations that we see as

flags or markers of variations, " Spritz

explained. " These could be the ones that cause

the disease or tell us about the ones that do. "

But NALP1 is probably only part of the picture.

" This can't be the whole

story, " Spritz said. " This

is one of probably many genes that predispose to autoimmunity, but it looks

like it may be involved in a pretty big way, which is why we were able to find

it. "

The gene is connected to the

body's primitive immune system, which is involved with the earliest responses

to outside attacks.

" It probably has a big

effect, and it probably interacts in some complex way with other genes and

other risk factors, " Spritz pointed out. " We know a lot about this gene. It

was not an anonymous gene that you would have to start from ground zero

studying. We know that it's part of the surveillance

system for attack by bacteria or viruses, part of the innate immune system. "

" This work is really nice

and elegant, and it's also provocative, " Gregersen

said. " It raises the issue of whether this gene

might be involved in more common disorders. "

He added that the research was

a good example of " a successful, family-based approach to gene

identification and an example of how new genes identified that way can raise

new connections among different diseases. "

Barb in Texas - Together in the Fight, Whatever it Takes!

Son Ken (32) UC 91 - PSC 99 Listed 7/21 @ Baylor Dallas