RESEARCH - Somatic mutations in the mitochondria of rheumatoid arthritis synoviocytes

[Guest guest]

Somatic mutations in the mitochondria of rheumatoid arthritis synoviocytes

R Da Sylva1 , Alison Connor2 , Mburu1, Keystone3 and

Gillian E Wu1

1Department of Biology, York University, Toronto, Ontario, Canada

2The Wellesley Toronto Arthritis and Immune Disorder Research Centre,

University Health Network, Toronto, Ontario, Canada

3Department of Medicine, University of Toronto, Mount Sinai Hospital,

Toronto, Ontario, Canada

Arthritis Research & Therapy 2005, 7:R844-R851 doi:10.1186/ar1752

The electronic version of this article is the complete one and can be found

online at: http://arthritis-research.com/content/7/4/R844

Abstract

Somatic mutations have a role in the pathogenesis of a number of

diseases, particularly cancers. Here we present data supporting a role of

mitochondrial somatic mutations in an autoimmune disease, rheumatoid

arthritis (RA). RA is a complex, multifactorial disease with a number of

predisposition traits, including major histocompatibility complex (MHC) type

and early bacterial infection in the joint. Somatic mutations in

mitochondrial peptides displayed by MHCs may be recognized as non-self,

furthering the destructive immune infiltration of the RA joint. Because many

bacterial proteins have mitochondrial homologues, the immune system may be

primed against these altered peptides if they mimic bacterial homologues. In

addition, somatic mutations may be influencing cellular function, aiding in

the acquirement of transformed properties of RA synoviocytes. To test the

hypothesis that mutations in mitochondrial DNA (mtDNA) are associated with

RA, we focused on the MT-ND1 gene for mitochondrially encoded NADH

dehydrogenase 1 (subunit one of complex I - NADH dehydrogenase) of

synoviocyte mitochondria from RA patients, using tissue from osteoarthritis

(OA) patients for controls. We identified the mutational burden and amino

acid changes in potential epitope regions in the two patient groups. RA

synoviocyte mtDNA had about twice the number of mutations as the OA group.

Furthermore, some of these changes had resulted in potential non-self MHC

peptide epitopes. These results provide evidence for a new role for somatic

mutations in mtDNA in RA and predict a role in other diseases.

Not an MD

I'll tell you where to go!

Mayo Clinic in Rochester

http://www.mayoclinic.org/rochester

s Hopkins Medicine

http://www.hopkinsmedicine.org

[Guest guest]

-

This sounds to me like this could be a very important link in the

discovery chain, if I am reading the techospeak correctly?

Jane

>

> Somatic mutations in the mitochondria of rheumatoid arthritis

synoviocytes

>

>

> R Da Sylva1 , Alison Connor2 , Mburu1,

Keystone3 and

> Gillian E Wu1

> 1Department of Biology, York University, Toronto, Ontario, Canada

> 2The Wellesley Toronto Arthritis and Immune Disorder Research

Centre,

> University Health Network, Toronto, Ontario, Canada

> 3Department of Medicine, University of Toronto, Mount Sinai

Hospital,

> Toronto, Ontario, Canada

>

> Arthritis Research & Therapy 2005, 7:R844-R851

doi:10.1186/ar1752

>

> The electronic version of this article is the complete one and can

be found

> online at: http://arthritis-research.com/content/7/4/R844

>

>

>

> Abstract

>

>

>

> Somatic mutations have a role in the pathogenesis of a number

of

> diseases, particularly cancers. Here we present data supporting a

role of

> mitochondrial somatic mutations in an autoimmune disease, rheumatoid

> arthritis (RA). RA is a complex, multifactorial disease with a

number of

> predisposition traits, including major histocompatibility complex

(MHC) type

> and early bacterial infection in the joint. Somatic mutations in

> mitochondrial peptides displayed by MHCs may be recognized as non-

self,

> furthering the destructive immune infiltration of the RA joint.

Because many

> bacterial proteins have mitochondrial homologues, the immune system

may be

> primed against these altered peptides if they mimic bacterial

homologues. In

> addition, somatic mutations may be influencing cellular function,

aiding in

> the acquirement of transformed properties of RA synoviocytes. To

test the

> hypothesis that mutations in mitochondrial DNA (mtDNA) are

associated with

> RA, we focused on the MT-ND1 gene for mitochondrially encoded NADH

> dehydrogenase 1 (subunit one of complex I - NADH dehydrogenase) of

> synoviocyte mitochondria from RA patients, using tissue from

osteoarthritis

> (OA) patients for controls. We identified the mutational burden and

amino

> acid changes in potential epitope regions in the two patient

groups. RA

> synoviocyte mtDNA had about twice the number of mutations as the OA

group.

> Furthermore, some of these changes had resulted in potential non-

self MHC

> peptide epitopes. These results provide evidence for a new role for

somatic

> mutations in mtDNA in RA and predict a role in other diseases.

>

>

>

>

>

> Not an MD

>

> I'll tell you where to go!

>

> Mayo Clinic in Rochester

> http://www.mayoclinic.org/rochester

>

> s Hopkins Medicine

> http://www.hopkinsmedicine.org

[Guest guest]

-

This sounds to me like this could be a very important link in the

discovery chain, if I am reading the techospeak correctly?

Jane

>

> Somatic mutations in the mitochondria of rheumatoid arthritis

synoviocytes

>

>

> R Da Sylva1 , Alison Connor2 , Mburu1,

Keystone3 and

> Gillian E Wu1

> 1Department of Biology, York University, Toronto, Ontario, Canada

> 2The Wellesley Toronto Arthritis and Immune Disorder Research

Centre,

> University Health Network, Toronto, Ontario, Canada

> 3Department of Medicine, University of Toronto, Mount Sinai

Hospital,

> Toronto, Ontario, Canada

>

> Arthritis Research & Therapy 2005, 7:R844-R851

doi:10.1186/ar1752

>

> The electronic version of this article is the complete one and can

be found

> online at: http://arthritis-research.com/content/7/4/R844

>

>

>

> Abstract

>

>

>

> Somatic mutations have a role in the pathogenesis of a number

of

> diseases, particularly cancers. Here we present data supporting a

role of

> mitochondrial somatic mutations in an autoimmune disease, rheumatoid

> arthritis (RA). RA is a complex, multifactorial disease with a

number of

> predisposition traits, including major histocompatibility complex

(MHC) type

> and early bacterial infection in the joint. Somatic mutations in

> mitochondrial peptides displayed by MHCs may be recognized as non-

self,

> furthering the destructive immune infiltration of the RA joint.

Because many

> bacterial proteins have mitochondrial homologues, the immune system

may be

> primed against these altered peptides if they mimic bacterial

homologues. In

> addition, somatic mutations may be influencing cellular function,

aiding in

> the acquirement of transformed properties of RA synoviocytes. To

test the

> hypothesis that mutations in mitochondrial DNA (mtDNA) are

associated with

> RA, we focused on the MT-ND1 gene for mitochondrially encoded NADH

> dehydrogenase 1 (subunit one of complex I - NADH dehydrogenase) of

> synoviocyte mitochondria from RA patients, using tissue from

osteoarthritis

> (OA) patients for controls. We identified the mutational burden and

amino

> acid changes in potential epitope regions in the two patient

groups. RA

> synoviocyte mtDNA had about twice the number of mutations as the OA

group.

> Furthermore, some of these changes had resulted in potential non-

self MHC

> peptide epitopes. These results provide evidence for a new role for

somatic

> mutations in mtDNA in RA and predict a role in other diseases.

>

>

>

>

>

> Not an MD

>

> I'll tell you where to go!

>

> Mayo Clinic in Rochester

> http://www.mayoclinic.org/rochester

>

> s Hopkins Medicine

> http://www.hopkinsmedicine.org

[Guest guest]

Yes, Jane, I think this is a very important discovery. Somatic mutations are

mutations that occur after conception. They are also called acquired

mutations.

Not an MD

I'll tell you where to go!

Mayo Clinic in Rochester

http://www.mayoclinic.org/rochester

s Hopkins Medicine

http://www.hopkinsmedicine.org

[ ] Re: RESEARCH - Somatic mutations in the mitochondria

of rheumatoid arthritis synoviocytes

> -

> This sounds to me like this could be a very important link in the

> discovery chain, if I am reading the techospeak correctly?

> Jane

>

>>

>> Somatic mutations in the mitochondria of rheumatoid arthritis

> synoviocytes

>>

>>

>> R Da Sylva1 , Alison Connor2 , Mburu1,

> Keystone3 and

>> Gillian E Wu1

>> 1Department of Biology, York University, Toronto, Ontario, Canada

>> 2The Wellesley Toronto Arthritis and Immune Disorder Research

> Centre,

>> University Health Network, Toronto, Ontario, Canada

>> 3Department of Medicine, University of Toronto, Mount Sinai

> Hospital,

>> Toronto, Ontario, Canada

>>

>> Arthritis Research & Therapy 2005, 7:R844-R851

> doi:10.1186/ar1752

>>

>> The electronic version of this article is the complete one and can

> be found

>> online at: http://arthritis-research.com/content/7/4/R844

>>

>>

>>

>> Abstract

>>

>>

>>

>> Somatic mutations have a role in the pathogenesis of a number

> of

>> diseases, particularly cancers. Here we present data supporting a

> role of

>> mitochondrial somatic mutations in an autoimmune disease, rheumatoid

>> arthritis (RA). RA is a complex, multifactorial disease with a

> number of

>> predisposition traits, including major histocompatibility complex

> (MHC) type

>> and early bacterial infection in the joint. Somatic mutations in

>> mitochondrial peptides displayed by MHCs may be recognized as non-

> self,

>> furthering the destructive immune infiltration of the RA joint.

> Because many

>> bacterial proteins have mitochondrial homologues, the immune system

> may be

>> primed against these altered peptides if they mimic bacterial

> homologues. In

>> addition, somatic mutations may be influencing cellular function,

> aiding in

>> the acquirement of transformed properties of RA synoviocytes. To

> test the

>> hypothesis that mutations in mitochondrial DNA (mtDNA) are

> associated with

>> RA, we focused on the MT-ND1 gene for mitochondrially encoded NADH

>> dehydrogenase 1 (subunit one of complex I - NADH dehydrogenase) of

>> synoviocyte mitochondria from RA patients, using tissue from

> osteoarthritis

>> (OA) patients for controls. We identified the mutational burden and

> amino

>> acid changes in potential epitope regions in the two patient

> groups. RA

>> synoviocyte mtDNA had about twice the number of mutations as the OA

> group.

>> Furthermore, some of these changes had resulted in potential non-

> self MHC

>> peptide epitopes. These results provide evidence for a new role for

> somatic

>> mutations in mtDNA in RA and predict a role in other diseases.

>>

[Guest guest]

Yes, Jane, I think this is a very important discovery. Somatic mutations are

mutations that occur after conception. They are also called acquired

mutations.

Not an MD

I'll tell you where to go!

Mayo Clinic in Rochester

http://www.mayoclinic.org/rochester

s Hopkins Medicine

http://www.hopkinsmedicine.org

[ ] Re: RESEARCH - Somatic mutations in the mitochondria

of rheumatoid arthritis synoviocytes

> -

> This sounds to me like this could be a very important link in the

> discovery chain, if I am reading the techospeak correctly?

> Jane

>

>>

>> Somatic mutations in the mitochondria of rheumatoid arthritis

> synoviocytes

>>

>>

>> R Da Sylva1 , Alison Connor2 , Mburu1,

> Keystone3 and

>> Gillian E Wu1

>> 1Department of Biology, York University, Toronto, Ontario, Canada

>> 2The Wellesley Toronto Arthritis and Immune Disorder Research

> Centre,

>> University Health Network, Toronto, Ontario, Canada

>> 3Department of Medicine, University of Toronto, Mount Sinai

> Hospital,

>> Toronto, Ontario, Canada

>>

>> Arthritis Research & Therapy 2005, 7:R844-R851

> doi:10.1186/ar1752

>>

>> The electronic version of this article is the complete one and can

> be found

>> online at: http://arthritis-research.com/content/7/4/R844

>>

>>

>>

>> Abstract

>>

>>

>>

>> Somatic mutations have a role in the pathogenesis of a number

> of

>> diseases, particularly cancers. Here we present data supporting a

> role of

>> mitochondrial somatic mutations in an autoimmune disease, rheumatoid

>> arthritis (RA). RA is a complex, multifactorial disease with a

> number of

>> predisposition traits, including major histocompatibility complex

> (MHC) type

>> and early bacterial infection in the joint. Somatic mutations in

>> mitochondrial peptides displayed by MHCs may be recognized as non-

> self,

>> furthering the destructive immune infiltration of the RA joint.

> Because many

>> bacterial proteins have mitochondrial homologues, the immune system

> may be

>> primed against these altered peptides if they mimic bacterial

> homologues. In

>> addition, somatic mutations may be influencing cellular function,

> aiding in

>> the acquirement of transformed properties of RA synoviocytes. To

> test the

>> hypothesis that mutations in mitochondrial DNA (mtDNA) are

> associated with

>> RA, we focused on the MT-ND1 gene for mitochondrially encoded NADH

>> dehydrogenase 1 (subunit one of complex I - NADH dehydrogenase) of

>> synoviocyte mitochondria from RA patients, using tissue from

> osteoarthritis

>> (OA) patients for controls. We identified the mutational burden and

> amino

>> acid changes in potential epitope regions in the two patient

> groups. RA

>> synoviocyte mtDNA had about twice the number of mutations as the OA

> group.

>> Furthermore, some of these changes had resulted in potential non-

> self MHC

>> peptide epitopes. These results provide evidence for a new role for

> somatic

>> mutations in mtDNA in RA and predict a role in other diseases.

>>