Prime culprit behind the onset of rheumatoid arthritis identified

[kristopher]

Study: Culprit leading to rheumatoid arthritis discovered

February 26, 2014
By RYOSUKE NONAKA/ Staff Writer

An international group of researchers is offering hopes of a cure for sufferers of rheumatoid arthritis, identifying the prime culprit behind the onset of the crippling disease.

This discovery could lead to the development of a drug for the first time to cure the autoimmune disease, in which a sufferer's immune system attacks his own tissues, instead of combating invading viruses and bacteria in the body.

The scientists, including researchers at Osaka University, have found that people susceptible to contracting rheumatoid arthritis developed the disease after cellular misfolded proteins are transported to the surfaces of cells without being processed into peptides. These proteins were processed within the cells in the bodies of healthy people.

“We can expect to develop a drug that is targeted at denatured proteins to dissolve them, or a method of examination that will allow doctors to make a diagnosis of the disease at an extremely early stage,” said Hisashi Arase, professor of immunology at Osaka University, one of the researchers.

The findings were carried in the online Proceedings of the National Academy of Sciences...

Autoantibodies to IgG/HLA class II complexes are associated with rheumatoid arthritis susceptibility

Significance

Cellular misfolded proteins are transported to the cell surface by MHC class II molecules via association with the peptide-binding groove without processing to peptides. We found that IgG heavy chain is transported to the cell surface by MHC class II molecules. Furthermore, IgG heavy chain associated with MHC class II molecules is recognized by autoantibodies in rheumatoid arthritis patients. Autoantibody binding to IgG heavy chain complexed with different MHC class II alleles was strongly associated with rheumatoid arthritis susceptibility conferred by certain MHC class II alleles. These findings suggest that misfolded proteins complexed with MHC class II molecules could be targets for autoantibodies in autoimmune diseases, which might be involved in autoimmune disease susceptibility.

Abstract
Specific HLA class II alleles are strongly associated with susceptibility to rheumatoid arthritis (RA); however, how HLA class II regulates susceptibility to RA has remained unclear. Recently, we found a unique function of HLA class II molecules: their ability to aberrantly transport cellular misfolded proteins to the cell surface without processing to peptides. Rheumatoid factor (RF) is an autoantibody that binds to denatured IgG or Fc fragments of IgG and is detected in 70–80% of RA patients but also in patients with other diseases. Here, we report that intact IgG heavy chain (IgGH) is transported to the cell surface by HLA class II via association with the peptide-binding groove and that IgGH/HLA class II complexes are specifically recognized by autoantibodies in RF-positive sera from RA patients. In contrast, autoantibodies in RF-positive sera from non-RA individuals did not bind to IgGH/HLA class II complexes. Of note, a strong correlation between autoantibody binding to IgG complexed with certain HLA-DR alleles and the odds ratio for that allele’s association with RA was observed (r = 0.81; P = 4.6 × 10?5). Our findings suggest that IgGH complexed with certain HLA class II alleles is a target for autoantibodies in RA, which might explain why these HLA class II alleles confer susceptibility to RA.

http://www.pnas.org/content/early/2014/02/19/1401105111.abstract

[Warpy]

1. That could lead to preventive medicine, certainly

What we RA gimps would really like is something that attacks those nasty inflammatory cytokines without attacking us in the process. The biologicals do a good job of it be many of us can't take those.

[diane in sf]

7. I have gout and have found driking cherry juice makes the symptoms go away

I started putting 3 ounces of cherry kombucha in with about 3 ounces of kefir as part of my breakfast. I haven't had any pain in my toes since I've been doing that. I'm also noticing an improvement in the fine articulation of movement in my feet with concurrent improvement in my balance.

[Warpy]

8. The whole mechanism for gout is very different

and relates to purines in the diet. In people with gout, those purines crystallize, especially in joints, causing swelling and severe pain.

The cherry juice isn't going to hurt you. Staying away from purines or taking medications to deal with them will also work.

[Fridays Child]

2. I wish I had the science background to understand this.

In any event, progress toward understanding and treating autoimmune disorders is exciting. I wonder whether this research has ramifications for other autoimmune conditions.

[Warpy]

4. I can boil it down a bit

They've known for a long time that people with RA tend to have a certain type of marker on their immune cells.

This goes a bit farther and states our cells admit cockeyed proteins that normal people's immune cells destroy while they're in the blood stream. Or their own cells turn the cockeyed proteins into usable substances. Our cells save them. Then our immune systems attack our own cells to get at the bad proteins. It makes sense.

I'd still prefer something that binds to cytokines and makes them inert so that we're not exhausted, depressed and in pain.

[Fridays Child]

6. So...

...treatment might involve targeting the bad proteins without destroying entire cells? And, when you refer to cytokines, are those the bad proteins?

My son has advanced ankylosing spondylitis. I know that this research is about RA but I wonder whether a similar mechanism is in play with AS.

Anyway, if RA is anything like AS, you're dealing with a lot of pain.

I hope that real help is on the horizon for you and for my son.

[truedelphi]

9. Thanks for the clear explantion about gout and cherry juice and the other

Matters you bring up. I know Cherry Juice works great with gout, as my mom had it and when I suggested she try cherry juice, she did and it worked.

I only have very mild seasonal arthritis, (not RA) and with Calif. in a drought, it doesn't act up much at all.

[VanillaRhapsody]

3. I am going tomorrow to get a specialist diagnosis of my own first Auto Immune Disorder

But not RA (so far) I have had allergies all my life.....I kind of had a feeling this was going to happen eventually sooner or later....I guess that day has come. I hope this will at least prevent the progression of these diseases....that's the part that sucks and most don't understand....they have no real idea what causes them and all they can do is try to stop progression and treat symptoms...

To think you stay relatively healthy (which I am just had a physical last month) but instead my body turns against me. I guess it wasn't happy with just being allergic to outside forces....now I get the pleasure of being allergic to me! Anyway....thanks for the chance to vent. There is still a small chance this is not Auto Immune disorder....I shall soon find out.

[Warpy]

5. They're incurable at present

but they're all treatable to one extent or another.

[jtuck004]

10. The treatments suck. And the side effects vary. Wife got a mrsa infection

in the shoulder of the arm they were doing her IV infusions in. Several weeks of high dollar antibiotics I had to giver her IV at home. The week of the last treatment she developed an allergy to the penicillin and dropped unconscious, in shock. I treated her, transported her when she was awake a little.

Now we are on another one, I give subq injections every week, medicine delivered by UPS. Drug company is making a LOT of money off of that one - as with most of the new ones.

What I would like is not only a cure, but some way to fix the damage it does to the body over the years. It just tears one up, and the fixes we have for that today comes with its own set of issues.