Deepening the search for clues to rheumatoid arthritis

November 9, 2009 By Ellen Clegg
X-ray image of the hand of a rheumatoid arthritis patient. Image courtesy Wikimedia Commons

( -- The gnawing pain of rheumatoid arthritis is a signal that the body’s immune system has hit the wrong target: its own cartilage and bone.

The disease, which affects about 1% of the adult population worldwide, has no clear root cause, and for many patients, the available therapies are not effective.

For reasons that science has yet to fully understand, cells that normally destroy foreign invaders like bacteria turn on the body itself, causing and eroding the delicate machinery that keeps joints supple. But the body also holds tantalizing clues, nestled in the DNA of each cell. In the 1970s, researchers found the first genetic risk factor for rheumatoid arthritis. A second risk factor was identified in 2003, and genome-wide studies have found a variety of others since then.

Now, scientists and clinicians at the Broad Institute of MIT and Harvard, and Brigham and Women’s Hospital, working with an international team, have widened the hunt, finding three new for the disease. They also identified four more that look like promising targets for further research. Their work was published online November 8 in the journal .

The researchers brought a powerful weapon to the hunt: A computer program called GRAIL allowed them to quickly comb through nearly three decades’ worth of scientific literature on PubMed, a free digital archive maintained by the National Institutes of Health since the 1960s.

Much like Google, GRAIL harnesses the power of computer algorithms to sift through a vast array of text - in this case, the program analyzed 250,000 published abstracts, or summaries, of studies on genes in humans and in other organisms such as the mouse.

"With GRAIL, you can take a list of genes and use the wealth of published literature and mine it for a common thread," said Soumya Raychaudhuri, a postdoctoral researcher at the Broad Institute who developed the program and who is first author of the paper. "GRAIL is fast and objective. There are 20,000 genes in the human genome, and none of us is an expert on all 20,000. GRAIL helps you parse the list really quickly and come up with promising candidates that you can then focus your attention on. It’s a way to focus one’s intellectual resources."

Hardier than any pair of human eyes, GRAIL, which is short for Gene Relationships Across Implicated Loci, scans study abstracts for references to regions of the genome suspected to play a role in rheumatoid arthritis and compares these with previously confirmed risk factors. The short list of new candidates can then be confirmed in laboratory studies.

Raychaudhuri and his colleagues used GRAIL to examine studies that uncovered single "letter" variations in the genome, known as single-nucleotide polymorphisms, or SNPs, from 179 regions of the genome thought to influence risk.. GRAIL gave each region a score, based on its relationships to genes in 16 regions that are already known to be associated with rheumatoid arthritis.

Twenty-two of these SNPs looked promising, so the scientists examined them in samples from thousands of patients with and without rheumatoid arthritis. Of the 22, the analysis found three new risk factors for rheumatoid arthritis, and four more that look like promising targets for further research. Many of these variants are in or near regions of the genome already associated with autoimmune diseases, such as lupus erythematosus, celiac disease, and type 1 diabetes.
"These SNP associations continue to clarify critical biological processes involved in RA pathogenesis," the authors wrote, including the deployment of the immune system’s most important "soldiers," T-cells and B-cells.

"It really helped us take a long list of potential genetic variants and focus in on a small number of them … to see if these are true rheumatoid arthritis risk alleles, or not," said Robert Plenge, assistant professor at Harvard Medical School and director of genetics and genomics in the Division of Rheumatology, Immunology and Allergy at Brigham and Women's Hospital. "It allowed us to disregard a lot of things that we didn’t think would be important and to focus on those that had a higher chance of being important," said Plenge, one of the paper’s co-authors.

Although the scientists note that GRAIL is limited because it relies on the descriptions in already published literature, they hope it will help define the biological pathways involved in rheumatoid arthritis.

"One of the big challenges for technologies like GRAIL is to get it to move beyond the abstracts and get to the full text. That’s one of my longterm goals," Raychaudhuri said. "But the hope of all of this is that it will help us figure out what the key pathways are that seem to predispose people to disease,"he said. "And hopefully with that, we’ll be able to identify drugs that are effective."

More information: Raychaudhuri S et al., Genetic variants at CD28, PRDM1, and CD2/CD58 are associated with risk, Nature Genetics, advance online publication, 08 November 2009 | doi:10.1038/ng.479

Provided by Broad Institute

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not rated yet Nov 09, 2009
Perhaps the re-searchers ought to focus more, on all the alien substances that's put into the human body, via DRUGS, injected under the guise of building immunity, aka, VACCINATIONS.

I believe many are aware, of the following and definite link; rheumatoid arthritis is a neurological disease, and there are likewise, many links to VACCINES, having very debilitating effects on the human neurological system.

We Have A Question About Vaccines.

4409 -- TOXIC mercury makes you smarter!

It ain't what you don't know that gets you into trouble. It's what you know for sure that just ain't so - Mark Twain (1835-1910)

Information compiled and provided by: Christopher-Peter: Maingot; without prejudice, malice aforethought, ill will, vexation, or frivolity.
not rated yet Nov 09, 2009
Ummm, neurology makes up most of the processes behind pain. You aren't making a very good argument here just because DRUGS and VACCINATIONS both affect the neurological system. So does SEX and CHOCOLATE and SMOG. Perhaps we should look at those instead based on your reasoning?

Also, did you think about looking back a couple hundred years before vaccines were around to see if people still had arthritis then? I'm guessing they did.

Quack quack.
not rated yet Nov 09, 2009
Flu Shot Reactions Worry Officials.
Almost 1,000 Canadians have suffered adverse reactions to the flu vaccine in the past two months, Health Canada has revealed – [dubbed oculo-respiratory syndrome].

Analysis of Relative Risks and Levels of Risk in Canada.
Scroll down to Table 3. and take note of the first eight or so causes of death.

From the Council On Foreign Relations (CFR) Symposium, on Pandemic Influenza: Science, Economics and Foreign Policy:

“What would work better…would be to say; there was a shortage (vaccine) and people would then tend to line up more, for something that’s in demand…ha, ha, ha, ha, ha.”

October 16, 2009
CFR admits false scarcity tactic to get people to take the H1N1 vaccine.

Quack, quack?

Information compiled and provided by: Christopher-Peter: Maingot; without prejudice, malice aforethought, ill will, vexation, or frivolity.
Nov 09, 2009
This comment has been removed by a moderator.
not rated yet Nov 09, 2009
Figures...when everything starts falling apart for folks like you...out comes the mention of conspiracy, in an effort to discredit anything further.

It is commonly believed that the Salk vaccine was responsible for halting the polio epidemics that plagued American children in the 1940s and 1950s. If so, why did the epidemics also end in Europe, where polio vaccine was not so extensively used? Of greater current relevance; why is the Sabin virus vaccine still being administered to children when Dr. Jonas Salk, who pioneered the first vaccine, points out that Sabin vaccine is now causing most of the polio cases that appear?

Verum Mos, Solvo Vos.

Information compiled and provided by: Christopher-Peter: Maingot; without prejudice, malice aforethought, ill will, vexation, or frivolity.
not rated yet Nov 09, 2009
More on POLIO Conspiracy...

The United States Centre for Disease Control (CDC) admitted that the vaccine has become the dominant cause of polio in the US today, with 87% of cases between 1973 and 1983 caused by the vaccine. More recently, 1980-1989, every case of polio in the US was caused by the vaccine. Doctors and scientists on the staff of the National Institute of Health during the 1950's were well aware that the Salk vaccine was ineffective and deadly. Some frankly stated that it was "worthless as a preventative and dangerous to take". The Salk "inactivated" or "killed-virus" was actually regulated to permit 5,000 live viruses per million doses.

In 1958 mass vaccination triggered a disastrous increase in polio, the highest being 700% in Ottawa, Canada. The highest incidence in the USA occurred in those states which had been induced to adopt compulsory polio shots.

We should really try and get back on topic though...Arthritis.
not rated yet Nov 09, 2009
fuzz54...why did you delete your last post?

It wasn't anything personal...really!


Archaeological evidence indicates that arthritis was known as far back as the earliest dynasties of ancient Egypt and possibly before that time.

Health Canada clearly states the health risks associated with ingesting fluorides (any drink with fluoridated water): Fluorides lead to SKELETAL FLUOROSIS, a progressive disease. Bones increase in density and become brittle. SYMPTOMS INCLUDE; pain, stiff joints, difficulty in moving, deformed bones and, a greater risk of bone fractures. [Caps, brackets-mine]

Arthritis and vaccines.

Arthritis & vaccine citations.

Breastfeeding protects against rheumatoid arthritis
not rated yet Nov 09, 2009
I have to agree, Fluoride is one of those "popular" treatments that everyone should use, it says so on the label and I saw it on tv so it must be true!
I guess that I must be an bit strange because I avoid it like the plague, but then my teeth are in fine conditition and my BMD is good.
Then again, I'm just a kid at 51, plenty of time to fall apart.
not rated yet Nov 12, 2009
fuzz54...why did you delete your last post?

It wasn't anything personal...really!

Physorg deleted my post. It violated forum guidelines, although it's hard to say which guideline.
not rated yet Nov 12, 2009
Oh, okay. I see that "being snarky" in comments is not allowed. I'm glad that this forum has such specific guidelines.
not rated yet Nov 14, 2009
Listen to this interview between Dr. Mercola and Dr. Larry Palevsky; a board-certified pediatrician trained at the New York School of Medicine...he compellingly and convincingly, provides sound, rational, scientific justification, as to why, you need to seriously reconsider the wisdom of choosing vaccines as an option to prevent against most diseases.

In part eight, at the 4 minute mark, specific mention is made, regarding vaccine ingredients and, arthritis, and also neurological reactions that I would not like to take the chance with...would you, really?

Expert Pediatrician Discusses Vaccines (Part 1)

Information compiled and provided by: Christopher-Peter: Maingot; without prejudice, malice aforethought, ill will, vexation, or frivolity.
not rated yet Dec 01, 2009
Just to re-visit the correlation between the POLIO VACCINE and perhaps POLIO itself.

Mutation of live virus in oral doses linked to 124 cases this year, experts say.
Aug 14, 2009 - The Associated Press.

Polio is spreading in Nigeria and health officials say; it's caused by the vaccine used to fight the paralyzing disease.

So far, 124 Nigerian children have been paralyzed this year — about twice those afflicted in 2008.

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