• Welcome to Phoenix Rising!

    Created in 2008, Phoenix Rising is the largest and oldest forum dedicated to furthering the understanding of and finding treatments for complex chronic illnesses such as chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), long COVID, postural orthostatic tachycardia syndrome (POTS), mast cell activation syndrome (MCAS), and allied diseases.

    To become a member, simply click the Register button at the top right.

Gene Mutation Study Sheds Light on Autoimmune Disease Development

Bob

Senior Member
Messages
16,455
Location
England (south coast)
Gene Mutation Study Sheds Light on Autoimmune Disease Development
Nov 19, 2014
http://www.genengnews.com/gen-news-...t-on-autoimmune-disease-development/81250616/

Researchers say they have discovered how a gene mutation can lead to diseases that occur when the immune system attacks the body by mistake. Understanding how these mechanisms work could help scientists to develop new treatments for autoimmune diseases such as Lupus and neurodegenerative conditions, including Motor Neurone Disease, according to the researchers, who published their study (“The RNA-Editing Enzyme ADAR1 Controls Innate Immune Responses to RNA”) in Cell Reports.

The team found that a mutation in the ADAR1 gene causes a defect in an alarm system in cells that normally protects the body from viruses and other infections. This means that the alarm system is tripped by the cell's own molecules, causing the immune system to attack. Some viruses encode their genetic material using RNA, which is also produced by our own cells when the genes encoded in our DNA are translated into proteins.
Mutations in the ADAR1 gene have been linked to a rare autoimmune disease called Aicardi-Goutieres Syndrome. The disease affects the brain and skin and most people who are affected have significant intellectual and physical problems. The syndrome usually takes hold in early childhood and is so rare that it is not known how many people are affected. However the disease shows significant resemblances to the much more common and less severe Lupus.

Read more:
http://www.genengnews.com/gen-news-...t-on-autoimmune-disease-development/81250616/

Press Release (same info):
http://www.ed.ac.uk/news/2014/immunedisease-171114
 

Bob

Senior Member
Messages
16,455
Location
England (south coast)
Research Paper:

The RNA-Editing Enzyme ADAR1 Controls Innate Immune Responses to RNA
Niamh M. Mannion, Sam M. Greenwood, Robert Young, Sarah Cox, James Brindle, David Read, Christoffer Nellåker, Cornelia Vesely, Chris P. Ponting, Paul J. McLaughlin, Michael F. Jantsch, Julia Dorin, Ian R. Adams, A.D.J. Scadden, Marie Öhman, Liam P. Keeganemail, Mary A. O’Connellemail
20 November 2014
Cell Reports. Volume 9, Issue 4, p1482–1494
DOI: http://dx.doi.org/10.1016/j.celrep.2014.10.041
http://www.cell.com/cell-reports/ab...m/retrieve/pii/S2211124714009103?showall=true

Full article is free to access:
http://www.cell.com/cell-reports/fulltext/S2211-1247(14)00910-3

Summary
The ADAR RNA-editing enzymes deaminate adenosine bases to inosines in cellular RNAs. Aberrant interferon expression occurs in patients in whom ADAR1 mutations cause Aicardi-Goutières syndrome (AGS) or dystonia arising from striatal neurodegeneration. Adar1 mutant mouse embryos show aberrant interferon induction and die by embryonic day E12.5. We demonstrate that Adar1 embryonic lethality is rescued to live birth in Adar1; Mavs double mutants in which the antiviral interferon induction response to cytoplasmic double-stranded RNA (dsRNA) is prevented. Aberrant immune responses in Adar1 mutant mouse embryo fibroblasts are dramatically reduced by restoring the expression of editing-active cytoplasmic ADARs. We propose that inosine in cellular RNA inhibits antiviral inflammatory and interferon responses by altering RLR interactions. Transfecting dsRNA oligonucleotides containing inosine-uracil base pairs into Adar1 mutant mouse embryo fibroblasts reduces the aberrant innate immune response. ADAR1mutations causing AGS affect the activity of the interferon-inducible cytoplasmic isoform more severely than the nuclear isoform.
 

Jonathan Edwards

"Gibberish"
Messages
5,256
Well, I'm glad you are out of your depth too here, Bob! Never heard of Aicardi-whatsisname syndrome but that does not mean it might not be a very interesting lesson in mechanisms. If lupus is just 'less severe' in comparison it seems good that A-G syndrome is so rare. So far I am not sure about the autoimmune connection but it might be very interesting to know what grossly inappropriate interferon production might do to the nervous system. I think maybe I need to look at this, but I am suspecting it may turn out to be complicated!

As an aside, I don't seem to get a flag up if someone does an @ to me. Not sure if some function is disabled (other than my memory for names and the nerves to my left foot that is).
 

Bob

Senior Member
Messages
16,455
Location
England (south coast)
As an aside, I don't seem to get a flag up if someone does an @ to me. Not sure if some function is disabled (other than my memory for names and the nerves to my left foot that is).
Ah, that explains why you always ignore me! Hehehe... You don't really, but perhaps there's alot of 'tags' (that's what they're called) that you've missed...
There's an easy fix... If you go to the following settings page, you can choose what alerts you receive:
http://forums.phoenixrising.me/index.php?account/alert-preferences

The specific one you're looking for is the fourth one down: "Tags you in a message". You need to select that if you want to be alerted when your name is tagged.

I've got all my options ticked/checked, so I recommend doing the same...
(Except that you receive so many 'likes' that perhaps you'll get overwhelmed with alerts if you select alerts for "Likes your message".)

And don't forget to click on 'save changes' at the bottom, when you've finished.
 
Last edited:

Jonathan Edwards

"Gibberish"
Messages
5,256
I've got all those ticked Bob but I don't seem to get the flags. Or maybe there's a delay. I need to look in to this.
 

wdb

Senior Member
Messages
1,392
Location
London
I don't think I had to do anything special to get tagged.

@wdb, can you help Jonathan? (wdb is our tech genius).

It all looks in order this end, at least the logs are showing tag alerts were sent and were viewed.
 

Jonathan Edwards

"Gibberish"
Messages
5,256
Thanks @wdb. It may be I am getting them but I have noticed in the past going back that I find tags I do not recall seeing. I doubt there is a major issue anyway. I did have a patch in September when my email went completely berserk so maybe that was it.