New Blood Test for Rheumatoid Arthritis: 14-3-3eta
New Rheumatoid Arthritis test based on blood marker 14-3-3η
Yesterday, April 9, 2013, Quest Diagnostics announced a new blood test for Rheumatoid Arthritis based on a new protein biomarker, 14-3-3η. The test is available in the U.S. only at Quest labs through an exclusive agreement with Augurex Life Sciences, Corp. Several studies have investigated the relationship between blood levels of 14-3-3η and RA. According to Quest, 14-3-3η outperformed Rheumatoid factor (Rf) and anti-citrullinated protein antibodies (anti-CCP) in identifying early RA. Quest is also offering all three tests (Rf, anti-CCP, and 14-3-3η) in a combined RA panel which could significantly increase sensitivity.
New tests needed to identify Rheumatoid disease earlier
Rheumatoid factor antibodies are commonly present with Rheumatoid disease, but may be present with other diseases or in up to 10 percent of the general population. About 30% of people diagnosed with RA are Rheumatoid factor negative or “seronegative.” Many who initially test negative with Rf eventually have a positive blood test. The anti-CCP test has been considered the most specific blood test for RA and a predictor of a more serious disease course. It is 90 to 95% specific and its sensitivity is about 80%; so about 20% of those with RA test negative.
Blood tests also needed to confirm disease activity
While higher Rf and anti-CCP may associate with aggressive disease, they are not reliable methods to assess current Rheumatoid disease activity. The blood tests most commonly used to confirm disease activity are erythrocyte sedimentation rate (sed rate or ESR) or C-reactive protein (CRP). ESR is often high during acute illness, especially with cancer. It is a measure of how many red blood cells settle in a test tube in an hour. CRP is a protein produced by the liver during periods of acute inflammation. However, CRP is influenced by environmental and genetic factors. Many people experience acute inflammation or damaging Rheumatoid disease while continuing to have normal CRP or ESR.
New blood tests for RA are urgently needed to improve lives
The application of a new blood marker for RA is significant. Early RA treatment seems to be more beneficial, but can only occur with early diagnosis, which has been elusive, in part due to absence of precise blood tests. However, as 14-3-3η is employed, we hope that it will provide better insight for early diagnosis and with regard to disease activity. Success in each of these areas will be established two ways: further study and use on a wide population of patients.
Recommended reading
- Accurately Measuring Rheumatoid Disease Activity
- 4 Benefits of a New ACPA Rheumatoid Arthritis Test
- The HAQ’s, the RAPID’s & the Rest: 3 Reasons It’s a Moot Point
- Rheumatoid Factor Test: Should We Rely on Rheumatoid Factor Levels?
I am so thankful to read this today. I have struggled with RA for over 10 years. My disease was initially diagnosed as Lupus because my RF was negative. My SED rate is never elevated, even though swelling and inflammation of joints is obvious to the eye and nodules are visible on x-rays. When my RF turned positive, true treatment of RA began….methotrexate, Enbrel, Remicade….all of these over a period of time. Over a year ago, I stopped all chemical treatments, I changed my diet, became vegetarian, and started some new natural tactics to try to combat the disease.This was in part due to the fact that my longtime Rheumatologist left his position. The changes worked well for a while, but I am starting to flare again. I would love to know for sure that RA is my diagnosis…and I would love to find a new Rheumatologist. I have visited two and they are so overworked and overwhelmed that patients are herded in and out like cattle.
This is in response to Erica I believe was the name 25 yrs old just recently found out she has RA and how not to let it take over,I was 23 but it didn’t really hit me bad til i was 26 my advice is find good Dr.’s first and I found out the hard way on a “good” day still remember you have RA and don’t over do it because you still can do damage to yourself and your joints and I always paid for it the next few days because I felt good one day I’d do as much as I could then suffer for a week after so find your limits and good Dr.’s and take care of your self I am 43 know I have learned how much I can do on the “good” days I hope this helped ease your mind because you’ll learn what and what not to do.
Hmmmmm…… I go to the Dr on the 24th. I think I’ll mentioned it to him. However, I think they do their own lab work right there. Oh well, its worth a mention. Now before or after I tell him I WANT a bioligic?!
I am thankful to hear this news. I just would like to know how soon these blood tests will be available. So many dr.s appear to be afraid to diagnosis this disease due to uncertainty of blood tests and so many of us continue to suffer without treatment until symptoms are much worse sometimes still not diagnosed . Thank you Quest looking forward to the tests!!!!Thank you RA Warrior for letting us know!!!!
I pray that this becomes available in the UK…..I have had one RF blood come back positive to the GP ..now the wait begins for an appointment to the Rheumatologist ….
I will follow this with much interest…..
Hi Kelly,
I’m not so sure this is that great of a test. 80% sensitivity and 90-95% specificity does not, in my book, make for a great diagnostic to identify true positives. Here is a little example I cooked up. Let’s take 10,000 people that get this test and let’s also assume the prevalence of RA in the population is 1%. So that’s 100 people with RA and 9900 without. Of the 100 with RA, 80 would test positive, 20 would test negative. Of the 9900 without RA 495-990 (1-specificity, 5-10%) would test positive for RA and 9405-8910 would test negative. Given these numbers you have between 575-1070 total people testing positive. Of those, 80 people, are true positives, thus the positive predictive value of the test is only 7.5%-13.9%. However, the negative predictive value is quite good at about 99.8%.
But then again, people like me don’t have positive RF or CCP yet have symmetric joint involvement, joint deformation, pain and fatigue. Explain that!
Best,
RaRAP
I’m in the car, but I’m not sure that’s the specs of the new test. Sounds like the specs of CCP test (80 sensitivity & 90 specificity)
My dctor uses the Vectra Da test to assess disease activity but I haven’t seen much about them on any of these sites. It is not used for diagnosis but checks 12 markers of disease activity level for RA.
Any idea how costly this one is? I hope it’s not in the same category as the Vectra test. With any of these tests, the number of false positives and especially false negatives is discouraging. It would be great to have something a little better to add to the testing arsenal.
Good question. I called around and these are the prices in central Florida – cash prices. Rf is $50 at hospital lab & $54 at Quest. Anti CCP is 130 $ at hospital lab & $126.88 at Quest. The new test 14-3-3eta is only available at Quest right now. It’s $120. Vectra (by Crescendo Bioscience) is more expensive as you said, but contains 12 biomarkers & the company has a very generous patient assistance program so that anyone who makes less than six times the poverty level gets a big break if insurance doesn’t cover. If my memory is right, the most a patient would pay is $96.
Hi Kelly and Kim,
My friend works at Quest in Ohio and she said that no patient pays anything over $20 for any tests. I don’t know how accurate that is or if it’s the same in all states.
I am so glad that there is a new test. I am printing the article and taking it to my doctor! I keep hearing my RF isn’t high enough and since the drugs are so hard on the body they don’t want to give them to me until my numbers are higher or when I have visible damage. Doesn’t make much sense to me at all but I feel hopeless and at their mercy.
Hi Tina,
I was just “diagnosed” with RA by a long-practicing, award-winning rheumatologist–but my symptoms are atypical, and he’s been honest with me that he’s “not actually sure what I have”–but that early treatment of RA is SO IMPORTANT to prevent future problems. He’s put me on Plaquenil because it’s the gentlest of the DMARDs, with the fewest side effects. I strongly suggest you follow your instincts on this and insist that your rheum provide some help–or get a new rheumatologist! The future with untreated RA is not a pleasant prospect.
This is really terrific news. After reading the article though I am left with a question that I hope some of you can help with. Does your number from the anti-CCP test indicate how severe your RA is or will be? My doctor told me my number but never said if it was an indicator as to the severity of my disease.
Kathy, that number is not an exact predictor, no. It is true that higher results are believed to be associated with aggressive disease. It is a generality, not a rule.
For many doctors, when they see patients with higher anti-CCP, they realize the person may need aggressive disease treatment.
Kathy,
You are right to be concerned about the presence of Anti-CCP and what your number is as well as the presence of RF and what you number is.
When both are present and high values (RF >20 and CCP >250), research shows that the disease course is often worse with more damage evident on radiographs then if these values are negative. Research has shown that particularly when anti-CCP is positive and high that this correlates with more aggressive disease course and damage evident on x-ray or MRI.
This information from the research doesn’t necessarily reflect how well individual people can do when their disease is treated aggressively. It just means that people with RF and CCP positivity LIKELY will have a worse disease course.
REFERENCES: ACPA (Anti-CCP antibodies) and Outcome in RA Disease
deRooy (2011) Predicting arthritis outcomes—what can be learned from the Leiden Early Arthritis Clinic? Rheumatology, 50, 93–100. doi:10.1093/rheumatology/keq230. http://rheumatology.oxfordjournals.org/content/50/1/93.long
Forslind (2004) Prediction of radiological outcome in early rheumatoid arthritis in clinical practice: role of antibodies to citrullinated peptides (anti-CCP). Annals of Rheumatic Diseases, 63, 1090-1095. doi: 10.1136/ard.2003.014233. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1755129/
Houseman (2012) Baseline serum MMP-3 levels in patients with Rheumatoid Arthritis are still independently predictive of radiographic progression in a longitudinal observational cohort at 8 years follow up, Arthritis Research & Therapy, 14, R30.http://arthritis-research.com/content/14/1/R30
Lee (2006) The Predictive Power of Anti-Cyclic Citrullinated Peptide Antibodies: Window into Understanding Gene/Environment/Immunity Interactions. The Journal of Rheumatology, 33(7), 1216-1218. http://www.jrheum.org/content/33/7/1216.citation
Mjaavatten (2010) The likelihood of persistent arthritis increases with the level of anti-citrullinated peptide antibody and immunoglobulin M rheumatoid factor: a
longitudinal study of 376 patients with very early undifferentiated arthritis, Arthritis Research & Therapy, 12, R76. http://arthritis-research.com/content/12/3/R76
Manivelavan (2012). Anti-Cyclic Citrullinated Peptide Antibody: An Early Diagnostic and Prognostic Biomarker of Rheumatoid Arthritis. Journal of Clinical and Diagnostic Research 6(8): 1393–1396.doi: 10.7860/JCDR/2012/4692.2367
http://pubmedcentralcanada.ca/pmcc/articles/PMC3471491/;jsessionid=45B3BA877D7F3186C6F6C1FAFB5C1FD8.thrasher?lang=en-ca
Willemze (2012). The influence of ACPA status and characteristics on the course of RA. Nature Reviews- Rheumatolology, 8, pp144–152. doi:10.1038/nrrheum.2011.204 http://211.144.68.84:9998/91keshi/Public/File/7/8-3/pdf/nrrheum.2011.204.pdf
Hope this helps. Unfortunately, my RF is 41 and CCP >500 – not good!!
Kelly – Just wanted to again say THANK YOU!! This article is exactly what I needed today. I am caught in side-effect heck right now and my really good RA doctor wants me to get a second opinion before we start another biologic. I am seronegative, and almost always have normal ESR & CRP numbers. I just needed the reminder that it didn’t have to be anything else and it is good to have as I prep for a round with a different doctor.
Good luck April. Thinking of you. Hang in there.
Kelly, Thank you so much for RA Warrior, I am learning so much! When you all say the rheumatoid factor is negative do you mean -1 or higher? Mine is 8.9 and CCP Antibodies is 3 but my Doctor says I am Seronegative. SED rate is usually around 60 to 80 and CRP is normally double but finally normal in March. Even though my RF is not negative could I still be Seronegative? She said she measures my disease activity using SED Rate and CRP. I have been in a constant flare since last June and still in denial I guess…maybe it is not RA. After biopsy I was diagnosed with Sarcoidosis in 2006. Kim
Hi Kim, Great question – there are various versions of these tests, so each lab should provide a “reference range” for the results they give. The reference range should show what is normal or what is high. So when you get a copy of the results, you can tell whether the number you got on that particular test at that lab is in the normal range. Normal range is what they mean by “seronegative” for Rf.
The term seronegative used to refer to Rf only, but since the anti-CCP has been widely used & shown to be more specific for RA,most doctors would apply term to the anti-CCP as well. Some doctors will still say a person is seronegative if they have a neg. Rf, even with a positive ccp test.
The fact that your sed rate and CPR are high looks like an indicator of inflammation – it does not correlate in some people, but you just said you have symptoms with it. I don’t know if sarcoidosis can cause those tests to be high too.
On another topic – It’s lucky for you, but I’m glad I’m not her patient because although I’m seropositive with sky-high anti-ccp, I usually have normal sed rate and CRP. From what we can tell, about 40% of patients are like that. With the majority of docs like yours who “measure disease activity using sed rated & CRP,” we’re actually in the same situation that the “seronegative” patients were years ago when they could not get treated.
Hi Kelly,
I am having a Vectra DA blood test on Tuesday. I was wondering if you knew anything about those? Thanks for this site! It has been so helpful!
Hey Kelly,
I am a little confused about this new blood test.I am not new to RA .I recently had the Vectra DA blood test I had it twice about three or four months apart the first came back with a low number for any activity , the second last week was a very high number ,which my Dr told me my RA was very active which I knew because of the way I felt .When I had the first test I felt bad then as well .The Doc said the test was 100% accurate. Have any others have those type of results.
Hi Bob,
I’m not sure what your doc would’ve meant by saying that your Vectra “test was 100% accurate.” I’d assume that the company who performs the test performed it correctly and reported it correctly, so it was accurate in that sense.
Is a test a true reflection of your disease activity? Sometimes.
There is NO test that is in itself a complete accurate measure of disease activity with rheumatoid disease.
Over the years, sometimes, doctors have taken useful tests like the Rheumatoid factor, the anti-CCP, the sedimentation (sed) rate, the CRP, x-rays, bone scans, ultrasound, MRI scans, swollen joint coutns, and many other things I can’t think of right now – – and misunderstood their role in caring for Rheumatoid patients – and used them to so-called “prove” whether a person actually has the disease, or whether his disease is active.
But there has not ever been a definitive test for RA / RD and it is sad when doctors do not know better than to take useful tools and use them as “weapons” against patients.
Back to your situation, Bob. No one can know your disease activity better than you. That’s why patient reported outcome measures are the most important tool in judging rheumatoid disease activity.
You can read more about measuring disease activity here https://www.rawarrior.com/tag/measuring-rheumatoid-disease-activity/
Or about patient reported outcome measures here https://www.rawarrior.com/tag/patient-reported-outcome-measure/
I had a Vectra DA test and the results said “low disease activity”. I knew this couldn’t be right because I could see inflammation in my joints and new symptoms were occurring. I asked a leading rheumatologist in the UK about these results. He said that the Vectra-DA test can be influenced by medications we’re taking, particularly corticosteroids. This made sense to me as I was on a number of DMARDS and prednisone at the time.
Within one month of having the Vectra-DA test, I had an ultrasound of hands and feet. The ultrasound showed worsening RA when compared to the test results I had a year earlier. I had 6 joints with active inflammation, an increase in erosions from 6 to 10, and areas of hypermia. Clearly my disease activity was very high.
I think the Vectra-DA test (in my case) is a waste of time. I have heard similar stories to yours. I just don’t think it is a reliable or valid test, unfortunately.
The European League Against Rheumatism (EULAR) just published guidelines in 2013 for the use of imaging in rheumatology. Their guidelines were based on a review of the research and literature. The use of MRI or ultrasound to assist with diagnosis and monitoring disease activity is known to be far superior to x-rays or clinical exam (a joint count). I am planning to request at least annual ultrasound of my hands and feet to monitor disease progression. I’ve been really pleased with the objective evidence ultrasound provides in my case. My CRP and ESR are always normal – which is known to occur in at least 40-50% of people with RA so that is not a good indicator of inflammation in my case.
Hey Kelly,
I believe when my Dr said the Vectra DA test was 100% accurate he meant as a tool to measure the disease’s activity
on a scale of 1-100.I called Cresendo Bioscience and spoke to their rep they clam to be correct on that test to be able to monitor RA activity.I only know that I have been off all RA drugs since April .I was on Remicade infusions (9 viles)
every 4 weeks.Please understand I am not defending the test .I was on Remicade for 2 1/2 years . I fired my last Rheumy in April and it has taken me awhile to find one that I trust. My CRP AND ESR as well have been normal .I was told by one Dr I was in remission when I was having a great deal of pain, the fatigue at times was unbearable he told me my pain was not RA because it was not in my hands or feet that was not the first time that happened . I don’t know if the test is going to be right all the time ,but it made a believer out of my Doc. When I told him I was hurting ,he agreed because the test showed my RA to be very active.Today I will call Cresendo Bioscience and ask them if the test can be compromised my certain drugs.Thanks Kelly for letting me comment.I appreciate all your time and work you put into keeping us informed .Now I am not sure about this test as well .
Bob West
Hi Bob,
I had a hunch that’s what your doctor implied. It’s frustrating that he believes that. Or that someone from CB told you that. I’m really sorry you’re going through this baloney on top of the disease, which is more than enough for anyone.
ONE – As a fellow patient, I’ll stand by your assessment of your disease any day, over any test anyone can put forth. (And the good people I’ve met at CB would agree with me, I think). This website was one of the first places that this test was discussed, and it has helped some patients to get treated when their docs refused to realize that they were suffering. Yet, I’ve warned from the beginning that it is not THE single test yet – that doesn’t exist. (That’s why I say docs must not use a “tool” as a “weapon.”)
TWO – Reading the research fully, the doctor’s opinion is not supported. There’s just not evidence to make that claim. And I give you my word that I’ll follow up on this story & continue to present the evidence. If a test existed to prove that at person even HAD this disease (much less his level of disease activity), I’d definitely write about that here. (Consider this – as far as I’ve been told, they don’t use the Vectra at Mayo Clinic – if it were THE ultimate test to judge the disease, wouldn’t they use it?)
Finally, to your question about the test results being “compromised by drugs,” the test is just a compilation of 12 tests in one, checking for levels of these things in your blood. The results are based on how much of each one is in your blood. The problem comes with individual differences in Rheumatoid patients. EITHER there are different strains of the disease causing us to have different antibodies OR our different immune systems cause us to create more of different biomarkers in response to the disease OR a combination of the two. (I don’t think anyone knows yet, but when we do, this nonsense of telling people it’s in their head or that they are in remission because of a low CRP or whatever can finally end – as long as there are no errors – which will be never…) If some part of your immune system responded in some way to some medication you took, then yes, it would be reflected in the test results. But in the end that shouldn’t matter if you are already aware of the disease activity, you already know it is high.
I’m not sure I’ve written about this before, but the one time I took the Vectra, it was in the middle of the Rituxan trial I was in. My disease activity did not improve during the year of Rituxan, but obviously some of my B cells (or many) were killed – because that’s what Rituxan does. And my Vectra results were not high. The test showed the Rituxan did something, just not what it needed to do to control my disease. That’s the reason different medications work on different people – it’s like we have a different “version” of the disease if our disease activity is mediated by a different biomarker. I hope I’ve made this clear for whoever reads this – patient, nurse or doctor, or salesperson – we don’t know half enough about this disease to be dismissing patients’ disease activity that is crippling them. That needs to stop, and we need to get on with helping people.
Take care, Bob.
Hey Kelly,
I once more thank you for your help I just pray that some of these Drs would look at all this information maybe it would change their way of thinking .I am going to push really hard that my Dr. check out RA Warrior !I will remind him every time I walk into his office!
Bob West
Bob have you had a recent ultrasound (or MRI) of your hands, feet, or joints you are concerned about? These advanced imaging techniques will show active inflammation, erosions, and hypermia – hallmarks of active disease. If rheumatologists only use clinical exam of joints or x-rays, they are not keeping up with the research that shows these measures are not as accurate as advanced imaging techniques.
Usually University Hospitals will have radiology departments with technicians and radiologists who are experienced in imaging people with RA/RD using MRI or ultrasound.
Here is the link to the EULAR 2013 guidelines on the use of imaging in rheumatology. We need all the tools we can to track disease activity using objective measures that are reliable and valid: http://ard.bmj.com/content/early/2013/03/20/annrheumdis-2012-203158.full.pdf+html
My CRP and ESR are always normal as well. The Vectra-DA test includes CRP as one of the 12 markers they assess.
I agree with Kelly’s analysis about the variety of pathophysiological mechanisms at work with this disease. That is why there are so many different drugs that address the different mechanisms of disease and not one set of diagnostic tools to diagnose or monitor disease activity.