The Pathogenesis of RA: A New Model | Arthritis Information

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Our conceptualization of rheumatoid arthritis assumes the disease develops in the context of a genetic predisposition and in the presence of certain environmental factors, with interactions between genes and environment leading to immune reactivity and clinical disease. RA is heterogeneous both clinically and etiologically, with two distinct subsets defined by the presence or absence of anticitrulline antibodies.

From RF to CCP 

RA is a criteria-defined, versus etiology-defined, disease, with one criterion being the presence of rheumatoid factor (RF), first recognized nearly seven decades ago. Although RF is present in 80% of patients, it is not specific. It also can be detected in up to 15% of healthy elderly people.

Citrullination is a posttranslational enzymatic process mediated by calcium-dependent peptidyl arginine deiminases in which positively charged protein arginine residues are converted to neutral citrullines, rendering the proteins more subject to degradation by proteolytic enzymes. In RA, increased citrullination is seen in the joints, lungs, and sites of extra-articular involvement as well as in many synovial proteins like fibrinogen, vimentin, and type II collagen. In normal synovial tissue, there is no expression of citrullinated molecules.

Increased citrullination as a manifestation of human disease was first identified in the lining and sublining layers of RA synovial tissue.

It had previously been shown that antibodies to cyclic citrullinated proteins (anti-CCP) are present in about 60% of RA patients, versus 2% of healthy controls and fewer than 10% of patients with other rheumatic diseases.

Citrullination is a common event in many physiologic processes, but antibodies in RA have preferential reactivity to proteins that have undergone posttranslational citrullination.

Further studies have shown anti-CCP antibodies are not only predictive of RA but also have been directly implicated in pathogenesis. Animal data suggest citrullination can alter the immunogenicity of “self” antigens. This is in contrast to RF, which does not seem to be directly proarthritogenic.

Blood repository data from Sweden and the Netherlands found that anti-CCP antibodies can be detected years before symptom onset; they increase in concentration as clinical disease approaches, and thereafter rarely disappear, even with treatment. Patients who are anti-CCP positive typically have a more severe disease course than do anti-CCP-negative patients, with a greater likelihood of erosive disease.

http://www.rheumatologynews.com/article/S1541-9800(08)70366-1/fulltext
I am one who was diagnosed based on positive anti-ccp. Why isn't this test standard for everyone when diagnosing RA? Considering the ramifications that a person who is positive anti-ccp has a more severe disease course, and that anti-ccp can be detected years before symptom onset, it is beyond me that this isn't a standard part of diagnosing RA. I wonder how many people who have been told for years that nothing is wrong with them and have normal blood tests but are not tested for anti-ccp? Again, I have to ask why??? To me it would be paramount that this becomes standard beginning with the PCP.

My dear friend is a family practice physician educated at Dartmouth. She is brilliant. She has fibromyalgia but has other symptoms which could indicate RA. I asked if she had her anti-ccp tested, and she had no idea what I was talking about. Incidentally, she did get it tested and it was negative. Shoot - I typed and it disappeared, so starting all over.
 
I'm also positive anti-ccp (and RF) but I think it's a fairly new test in the U.S. so maybe isn't identified in some areas as being needed?   Eventually, I  hope the word gets out and it becomes standard along with RF and CRP, etc.    I wish it wasn't an indicator of severity down the road, but I guess I'm lucky that my first RD tested for this and I'm being treated aggressively, so hopefully that will help in the long-term.  
I "think" I am negative on most everything including the CCP stuff but clearly have erosive RA on MRI. I'm CCP negative and I'm a smoker.  So, at least for me, this guy is way off. 
 
I did like this part tho -
 
Future Research 

Because anti-CCP antibodies can be present for many years before disease develops, we postulate that there is a need for a second event such as trauma or viral infection that causes transient inflammation and expression of citrullinated proteins in the joints. This remains to be proven, along with a number of other aspects of the process of citrullination.

For example, we have not yet identified exactly which molecules are the targets of immune events in the lungs, nor do we know whether these immune events can be triggered elsewhere than the lungs or why it is that joints are targeted by these immune reactions. However, the framework we have developed should permit further studies on the role of adaptive immunity and the interaction between genes and environment in this subset of rheumatoid arthritis.

 
Yep, I'd like to know which molecules are the targets of immune events are too.
 
Pip
[QUOTE=graciesmom]I am one who was diagnosed based on positive anti-ccp. Why isn't this test standard for everyone when diagnosing RA?
 
This is my pet peeve about rheumatology - no standardization in testing or treatment.  It's a joke. 

well the ACR just came out with their new updated treatment guidelines and people complained because they were too regimated.  I think Suzanne said it was too many circles and arrows.  others complained because AP was virtually ignored.  you can't please everyone.  It includes what tests need to be run with each drug

http://www.rheumatology.org/publications/guidelines/recommendations.pdf 

they are also reviewing the diagnositic criterea to include the anti ccdp.  don't forget that test has been around less than 5 years.  it needed studies like these to validate it
I printed off the guidelines when it was originally posted and my treatment followed their new guidelines.   Made me feel better in that it took away doubt in whether the course I'm on was right or not for me.   It may very well be that RA is different for everyone and treatment for one may not work for another, but isn't it better to have some standards in place?  [QUOTE=buckeye]

well the ACR just came out with their new updated treatment guidelines and people complained because they were too regimated.  I think Suzanne said it was too many circles and arrows. 

[/QUOTE]

The circle and arrows were for treatment options.  I agree diagnostic testing should be standard, as well as what baseline tests are done.  And TB testing prior to immune suppression, etc.


For the most  part diagnostic testing is fairly standard with the exception of the anti ccp.  and I think we will see that added around the ACR meeting.  Th eonly reason it hasn't been is the shear newness of the test and the need for wider spread validation.

The new treatment guidelines, despite the circle and arrows
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