The most recognized differences in RA cases are between seropositive and seronegative disease, according David S. Pisetsky, MD, PhD, professor of medicine and immunology at Duke University School of Medicine in Durham, N.C.
Seropositive means that blood tests show the presence of anti-cyclic citrullinated peptides (anti-CCPs), also called anti-citrullinated protein antibodies (ACPAs). Anti-CCPs are antibodies produced against proteins in the body undergoing a molecular change in structure called citrullination. They are present in approximately 60 to 80 percent of people diagnosed with RA. Studies have found that, for many people, the antibodies precede the development of clinical symptoms by 5 to 10 years. If you have symptoms consistent with RA and a positive test for the antibody, an RA diagnosis is almost a certainty.
Previously, seropositivity was defined in terms of an antibody called rheumatoid factor (RF). Rheumatoid factor is an antibody directed to sites on other antibodies and can be detected by a variety of tests. While most patients with anti-CCP antibodies are also positive for rheumatoid factor, the RF antibody can occur in patients with many other conditions, including infection. Anti-CCP is more specific for RA and is becoming the preferred test for making this distinction.
Seronegative means that tests don’t show the presence of these antibodies in your blood. “You can have RA without being seropositive, but it is easier to meet the criteria if you are positive,” says Dr. Pisetsky.
Aside from the presence or lack of antibodies, there are a few other differences in people with seropositive and seronegative RA. For one, people with seropositive, or anti-CCP-positive, disease have a common sequence of amino acids called the shared epitope. This shared amino acid sequence is encoded in the human leukocyte antigen (HLA) genetic site, or locus, which produces proteins that control immune responses. It is not known how the amino acid sequence contributes to RA, but it has been proposed that it attaches to parts of proteins called citrullinated peptides, and therefore contributes to the production of anti-CCP antibodies. Interestingly, smoking is strongly related to the development of RA in patients with the shared epitope. Scientists believe that smoking causes inflammation in the lung, which leads to protein citrullination which in turns induces anti-CCP antibodies in genetically susceptible people with the shared epitope.
Other differences have to do with the risk factors associated with seropositive and seronegative disease.
While one might predict that anti-CCP-negative RA would be milder disease, that isn’t always the case. And although it is unlikely that a person with seronegative RA will ever turn positive, it is possible for people with seronegative disease to eventually be diagnosed with a different disease altogether, Dr. Pisetsky says.
Dr. Pisetsky gives these examples:
- A person diagnosed with seronegative RA may eventually develop a skin rash that would cause the doctor to change the diagnosis to psoriatic arthritis.
- Joint fluid tests in what appears to be RA could lead to a diagnosis of chronic gout.
- Osteoarthritis can sometimes be confused with seronegative RA.
Other conditions you might have:
- Ankylosing spondylitis
- Juvenile arthritis
- Psoriatic arthritis
- Reiter’s syndrome (reactive arthritis)
Complete Blood Count
What it measures:
- Red blood cells, which carry oxygen from your lungs to your body
- White blood cells, which fight infection
- Hematocrit, a measurement of how much red blood is in your system
- Hemoglobin, a protein that helps your blood carry oxygen
- Platelets, which help your blood clot
What it means: It helps your doctor decide if your treatments or the disease itself is causing other problems like anemia. It also checks for side effects cause by some medications.
Other conditions you might have:
Creatine Kinase (CK)
What it measures: Levels of the muscle enzyme creatine phosphokinase (CPK)
What’s normal: Levels vary by age, gender, and race. Your doctor will tell you what your results mean.
What it means: You might have an inflammatory muscle disease. Higher levels of CPK can also show up after trauma, injections into a muscle, muscle disease due to an underactive thyroid, and while taking certain medications such as cholesterol-lowering drugs called statins.
Other conditions you might have:
- Heart attack
- Muscular dystrophy
- Early pregnancy
What it measures: More than 30 blood proteins that work together in your immune system during an inflammatory response. Complement proteins can get used up during this process.
What it means: Lower levels of all three components signal lupus and vasculitis, or inflamed blood vessels. They also give clues about RA. If you have lupus with kidney disease, your doctor may continue to give you this test because levels rise and fall along with disease activity.
- Seropositive & seronegative
- What is seropositive/seronegative?
- What do the test results mean?
- Does a positive rheumatoid factor or anti-CCP mean you must have RA?
- Does this test tell me how severe my arthritis is likely to be?
- What differences are there between people that are seropositive and seronegative?
- Does this affect the medications that will work for me?
- 10 Essential Facts About Seronegative Rheumatoid Arthritis
- Understanding Rheumatoid Arthritis Lab Tests and Results
- What is meant by Seronegative Arthritis?
- Key differences between people that are seropositive and seronegative?
Seropositive & seronegative
The diagnosis of any disease usually progresses along a well defined path that has three parts: a history of the complaint, blood tests and, usually, imaging (x-rays or scans). “Seropositive/seronegative” is a term that refers to the results of blood tests.
What is seropositive/seronegative?
The blood test that is ordered by the doctor in order to help establish the diagnosis of rheumatoid arthritis (RA) is looking for the presence of two proteins in the blood. One of them is called rheumatoid factor (RF). This is a very old but tried and tested investigation that was first introduced into rheumatology in the 1940s. The other test is called anti-CCP (or ACPA) and is more recent. Anti-CCP is more sensitive than RF and may appear much earlier in the course of RA.
What do the test results mean?
The presence of either of these tests may indicate that RA is present. However seropositivity is only one criterion of several that makes the diagnosis of RA likely (some of the other criteria are outlined in the next section). If the other criteria for the diagnosis are present then seropositivity is an additional clinching factor. A positive anti-CCP test is marginally stronger than positive RF test for the diagnosis.
Does a positive rheumatoid factor or anti-CCP mean you must have RA?
A positive RF or anti-CCP test does not mean that you have RA. Other features must be present such as symptoms of pain and swelling in the joints, involvement of many joints with inflammation, morning stiffness in the joints for longer than 45 min, x-ray evidence of the characteristic bone damage in the joints and extra-articular features of RA (meaning features that are outside the joints), such as nodules. Other blood tests commonly used prior to diagnosis include ESR and CRP, which measure the amount of inflammation in the joints. For more information on blood tests please see our article: ‘Laboratory tests used in the diagnosis and monitoring of rheumatoid arthritis.’
Does this test tell me how severe my arthritis is likely to be?
As a rule patients who are seropositive for RF and/or anti-CCP are more likely to have more severe RA but neither of these tests can accurately predict the future course of the disease in an individual patient.
What differences are there between people that are seropositive and seronegative?
As well as seropositive patients having a greater likelihood of developing more serious disease, they are also more likely to have extra-articular complications (such as nodules and vasculitis – see individual NRAS articles for more information) than those who are seronegative. Patients seronegative for RF and anti-CCP may have a different form of inflammatory arthritis for example psoriasis related arthritis or a spondyloarthropathy.
Does this affect the medications that will work for me?
Whilst the efficacy of most medications for RA is not affected by whether someone is seropositive or seronegative, evidence suggests that patients who are seronegative for both RF and anti-CCP do not respond as well to rituximab as patients who are sero-positive for one or both.
References available on request
Rheumatoid arthritis (RA) is a systemic inflammatory disease characterized by joint pain and swelling. It’s a chronic, progressive disease, which, if left untreated or undertreated, may result in functional debilitation and/or erosive joint damage. Complicating matters is the absence of a single definitive test that can diagnose RA. Instead, the standard criteria used to classify a patient with RA is a score based algorithm that includes the presence of at least 1 swollen joint not explained by a different etiology and which takes into account the number and size of joints affected, symptom duration, an abnormal test result for acute-phase reactants, and whether the patient is seropositive or not.1
Seropositivity refers to the presence of 1 or both of the autoantibodies rheumatoid factor (RF) and anticitrullinated protein antibody (ACPA) circulating in the blood. The majority of patients with RA are seropositive, with 50% to 70% of RA patients seropositive for ACPA and 65% to 80% seropositive for RF.2-4 Traditionally, serological status has been used to classify 2 subgroups of patients within the greater heterogeneous population of patients with RA.
These 2 subgroups—those with seronegative or seropositive RA—have typically been described to exhibit distinct courses of disease progression and response to therapy. Findings from numerous analyses of clinical studies have suggested that seropositive patients tend to exhibit a more severe course of disease progression and a poorer prognosis, typified by a greater number and earlier development of joint erosions and the need for more aggressive therapy than seronegative patients.2,5 Given the breadth of data describing the typical course of seropositive RA, it’s not surprising that seronegative RA in comparison is generally believed to be less aggressive and less severe than its seropositive counterpart.2 As a result, a diagnosis of seropositive RA may lead to a perception of more severe disease, thus justifying a more intensive treatment approach than a diagnosis of seronegative RA, which may be perceived as milder.6
This perception, however, is being challenged by recent studies providing new information on the clinical characteristics and outcomes of seronegative patients. The Dutch BehandelStrategieën (BeSt) study was designed to assess the outcomes of 4 Disease Activity Score (DAS)-steered treatment strategies in patients with recent onset RA. In a subanalysis, ACPA negative patients (n=184) had significantly greater disease activity and worse functional ability (as measured by DAS and the Health Assessment Questionnaire, respectively) than ACPA positive patients (n=300) at the outset of the study. Despite this, ACPA positive patients had greater joint damage, as measured by radiographs at baseline, compared to ACPA negative patients. After 8 years of follow-up, both groups had similar clinical responses to DAS-steered treatment, including a similar level of reduction in disease activity and similar level of functional ability. ACPA positive patients, however, exhibited greater progression of joint damage over time than ACPA negative patients.7
Another study, by the Canadian Early Arthritis Cohort (CATCH) study investigators, reported similar trends but also some important differences between seropositive and seronegative patients. Data were analyzed from 841 patients diagnosed with early RA (defined as symptom duration lasting between 6 weeks and 1 year) and undifferentiated inflammatory arthritis.8 About one-quarter of the patients in the cohort were seronegative. The study authors found that several measures of disease severity, including the number of swollen or tender joints and the presence of joint erosions as revealed by radiographs, were significantly higher in seronegative patients than in seropositive patients at baseline. Moreover, the disease duration from symptom onset was significantly shorter in patients who were seronegative as compared to those who were seropositive.
Both sets of patients were being treated similarly at baseline and throughout the study: greater than 85% of patients were on disease-modifying antirheumatic drugs (DMARDs) at baseline and 94% were on DMARDs at the 2 year follow-up. After 2 years, the seronegative RA patients had a significantly greater improvement in several measures of disease activity and had less erosive disease than those with seropositive disease.8
The CATCH study results, considered along with the results of previous studies, highlight the fact that seronegative RA patients are themselves a heterogeneous group, according to Vivian Bykerk, MD, a rheumatologist at the Hospital for Special Surgery in New York City, and a CATCH study author. “If a patient is classified as seronegative, it doesn’t necessarily mean we can predict their response to therapy. Some respond well to treatment and others are more difficult to treat.”
Part of the issue, Dr Bykerk explained, is that some of the patients who are classified as seronegative are actually unrecognized seropositive patients. Levels of autoantibodies in these patients may have been too low to be detected by standard methods, or autoantibodies other than RF or ACPA may be playing a role. For example, antibodies targeting carbamylated proteins have been identified in the sera of more than 45% of patients with RA.9 Interestingly, anticarbamylated protein antibodies were identified in 16% of RA patients who were ACPA negative, and the presence of such antibodies in these patients predicted a more severe disease course.9
The BeSt and CATCH study findings provide new perspectives on the heterogeneity of the seronegative RA patient population. Based on these data, RA patients classified as seronegative may indeed experience a level of disease activity that is as severe, or more severe, than patients who are seropositive, and thus may benefit from the type of aggressive treatment strategies that are more routinely used to treat seropositive patients.7,8
Published: March 20, 2015
10 Essential Facts About Seronegative Rheumatoid Arthritis
Historically, a key blood test to determine whether a person has rheumatoid arthritis checked for the presence of rheumatoid factor (RF): antibodies produced by the immune system that can attack healthy joints and tissues. More recently, an additional antibody called the anti-cyclic citrullinated protein (ACPA) has been considered a marker.
But now, the presence of RF or ACPA is no longer considered necessary for a rheumatoid arthritis diagnosis. When RF and ACPA are negative, but a person has symptoms similar to those of rheumatoid arthritis, seronegative arthritis can be diagnosed. People who have either RF or ACPA antibodies have seropositive RA.
Here are 10 things you should know about seronegative rheumatoid arthritis:
1. Doctors Rely on Symptoms to Diagnose Seronegative RA, Not Just the Results From Blood Tests
Since blood work doesn’t tell the whole story, your doctor will want to find out if you’re experiencing these key symptoms:
- Morning stiffness for more than an hour in your hands, knees, elbows, hips, feet, or ankles that lasts at least six weeks
- Joint swelling, tenderness or pain, and sometimes redness. Typically, RA affects distal joints symmetrically.
- Symptoms that appear symmetrically across the body and in multiple joints
- Chronic inflammation
- Morning stiffness that lasts longer than 30 minutes
X-rays can also help your doctor make a diagnosis by showing signs of erosions or other boney changes.
2. The Presence or Absence of RF or ACPA Doesn’t Make or Break an RA Diagnosis
Testing for rheumatoid factor in people suspected of having RA was popularized in the 1960s, and experts still don’t fully understand the exact link between these factors and the development of the disease. RF can be positive in multiple diseases, such as Hepatitis C, endocarditis, and multiple myeloma.
“Rheumatoid factor clearly plays a role in how serious rheumatoid arthritis the disease can be,” says John J. Cush, MD director of clinical rheumatology for the Baylor Scott & White Research Institute and a professor of medicine and rheumatology at the Baylor University Medical Center at Dallas. A newer blood test checks for ACPA, which appear to be more closely linked to the development of the disease than RF. In fact, a study published in July 2016 in the journal Autoimmunity Reviews says that ACPA antibodies represent an independent risk factor for developing RA. Having ACPA suggests there’s a genetic risk factor for the disease, but it’s not necessary for either antibody to be present in the blood for a diagnosis of seronegative RA.
3. More Than One-Third of People With RA Have Been Diagnosed With the Seronegative Type
While it’s still far more common to receive a seropositive diagnosis, a study published in August 2016 in the journal Rheumatology found that 38 percent of patients are diagnosed with seronegative RA.
RELATED: Rheumatoid Arthritis Myths Debunked
4. People With Seronegative RA Often Have Different Symptoms
The conventional wisdom is that seropositive patients have more severe symptoms, but recent studies suggest that the difference between the two forms of the disease may have more to do with the joints affected than with the severity of the RA symptoms. And a report published in June 2016 in BMC Musculoskeletal Disorders found that further research is needed to better understand the long-term outcomes of patients with seronegative RA.
5. Seronegative RA Could Become Seropositive Down the Road
Your rheumatoid arthritis markers may change over time from negative to positive. Many people with seronegative rheumatoid arthritis develop RF or ACPA — often within the first two years of diagnosis, says Dr. Cush, noting that as many as 80 percent of seronegative cases will become seropositive over time. Some cases develop into other autoimmune disease as well.
6. Seronegative Rheumatoid Arthritis Doesn’t Need to Be Treated Differently Than Seropositive
“Whether you are diagnosed with negative or positive, be aggressive in treatment and stay ahead of the disease,” advises Cush. The purpose of treatment in either case is to lessen pain and slow or prevent progression. “Remission as early as possible is the goal,” he adds.
Standard drug therapy in early disease includes nonsteroidal anti-inflammatory drugs, such as ibuprofen (Advil or Motrin) or Celebrex (celecoxib); Plaquenil (hydroxychloroquine), a medication that belongs to a class of medicines known as a disease-modifying antirheumatic drugs (DMARDs); and Trexall (methotrexate), a powerful drug also used to treat certain forms of cancer that works as an immunosuppressant.
7. Seronegative RA May Not Be the Correct Diagnosis
According to Cush, a small percentage of people with the seronegative form of RA will go into remission in the first year or two, and in some people the disease will progress — either mildly or severely. Others will not respond to conventional treatment, which may be because they don’t have RA at all. Spondyloarthritis conditions, which often affect the spine, are sometimes mistaken for seronegative rheumatoid arthritis.
8. New Symptoms May Change the Diagnosis
Eventually, people with seronegative disease may be diagnosed with a different disease altogether, according to the Arthritis Foundation. If, say, a person diagnosed with seronegative RA develops a skin rash, her diagnosis might change to psoriatic arthritis. Other changes or new test results could lead to a new diagnosis of chronic gout or osteoarthritis.
9. There Is No Way to Predict the Future Severity of Seronegative RA
Forecasting how any disease may progress is extremely difficult. Whether you’re diagnosed with seronegative or seropositive, there are no set expectations of how either form of the disease will play out in an individual. “I don’t know which patients I see will have mild symptoms or who will have horrible ones. But if I could choose, I would rather see a patient be diagnosed with seronegative, because it can have a milder course,” says Cush.
10. Seronegative RA Is Sometimes Linked to Having Higher Levels of Inflammation Than Seropositive
In a European study of 234 people who had both types of rheumatoid arthritis and had experienced symptoms for less than two years, those with seronegative RA showed higher levels of inflammation and more affected joints, according to a study published in April 2016 in Annals of the Rheumatic Diseases.
Understanding Rheumatoid Arthritis Lab Tests and Results
Rheumatoid arthritis (RA) is a chronic autoimmune disease that primarily affects the joints, but can affect other parts of the body. Diagnosing and managing RA involves clinical evaluation by a rheumatologist, as well as several different laboratory tests that require blood work. The results of these tests may be used in two ways:
- To confirm the presence of the RA.
- To determine how active the disease is.
The doctor and healthcare team use the results of these tests to guide treatment options for each patient. In turn, understanding how the results of blood tests used to monitor RA and its treatment can help patients better able to manage their RA.
Rheumatoid factor (RF) was the first autoantibody to be discovered in people with RA. (Autoantibodies develop in response to the body’s own tissue, and are characteristic of autoimmune diseases, such as RA.) Despite the name, however, RF is not specific to RA, and there are many factors that can impact RF lab results. About 20% of those with confirmed RA will not have an abnormal RF test, while 5% of people who do not have RA will have an abnormal RF test. Negative levels do not exclude the disease, and positive levels do not guarantee the diagnosis.
The normal range of RF is from 0-20 u/ml. RF above 20 u/ml is not considered enough to diagnose RA, as there other reasons the RF level may be elevated. Some conditions and medical procedures that can raise RF levels include: other autoimmune diseases, certain chronic infections, diabetes, bacterial endocarditis, cancer, normal aging, vaccinations and transfusions. It’s important to note that once the RF level is elevated, it will often remain so even if the disease goes into remission.
Anticyclic Citrullinated Peptide
Another test which is ordered when rheumatoid arthritis is suspected is the anticyclic citrullinated peptide (anti-CCP). The normal level of anti-CCP is less than 20 u/ml. A level above 20 suggests the possibility of RA. As with rheumatoid factor, some people with positive anti-CCP antibody will not have RA, but this test is somewhat more specific for RA than the rheumatoid factor. The higher the levels of anti-CCP antibody, the more likely it is to suggest RA.
This test is 97% specific for RA if it is present. Once a patient develops a positive anti-CCP, it will usually remain positive, despite remission.
About 20% of RA patients are seronegative, meaning that their RF and anti-CCP lab results both continue to come back negative. In these cases, the physician makes the diagnosis based on physical examination and imaging.
RF and anti-CCP are not used to monitor disease activity, because they both tend to remain positive despite remission. Once the diagnosis of RA has been made and confirmed, these tests are not repeated.
Sedimentation rate (also known as erythrocyte sedimentation rate or ESR), is a crude measure of inflammation. It is calculated by measuring the rate at which red blood cells sediment in a test tube in one hour. Normal levels for men range from 0-15 mm/hr to 0-20mm/hr and for women 0-20 mm/hr/ to 0-30mm/hr, depending on age – higher for people over the age of 50). The ESR rate is not specific for RA, and there are many factors that can interfere with the results, such as bad processing, an infection, and aging in patients over the age of 50.
C-reactive protein is another measure of clinical inflammation. The normal measurement is less than 1.0 in many labs. This test, however, can be influenced by factors such as obesity and infection and is not specific to RA.
Both ESR and C-reactive protein are non-RA-specific measures of inflammation. Both tests are used to test disease activity; when they are high, this suggests that the disease is very active (assuming no other causes for high results, such as infection, are present). The healthcare team orders these labs regularly to monitor the patient’s disease and check how his or her medications are working.
Complete Blood Count
A complete blood count (CBC) test looks at red and white blood cell counts. Below are the normal measurements in our lab – other labs may well have their own set of normal values.
White cell blood count (WBC)
Red cell blood count (RBC)
Platelets Normal Values
3.8 – 10.8
3.8 – 5.1
11.7 – 15.5
The CBC tests help to inform the healthcare team about side effects of treatment and any secondary consequences of RA, such as anemia. If the patient’s hemoglobin levels indicate anemia, this will be further investigated looking for its cause.
Complete Metabolic Panel
A complete metabolic panel is used to monitor kidney and liver function, in order to assess whether changes to medication must be made or whether they are working well. A complete metabolic panel measures sodium (Na), potassium (K), chloride, glucose, creatinine (a measure of kidney function), and AST and ALT (markers of liver function).
Both the CBC and the complete metabolic panel are used to monitor disease activity as well as side effects and efficacy of medication.
With these laboratory tests as a guide, the healthcare provider may need to make adjustments to the patient’s medications and RA treatment. Laboratory tests provide important information in the diagnosis, management and treatment of rheumatoid arthritis. By becoming informed about the normal values for tests, as well as their own numbers, patients with RA can better communicate with the health care team and gain a better understanding about some of the information that is used in developing and monitoring their treatment plans.
Learn more about the HSS Early RA Support and Education Program, a free support and education group, developed specially for people recently diagnosed with RA and early RA.
Summary by Lysa Petrsoric, MPH, MSW, April 20, 2015
Edited by Nancy Novick.
Monica Richey, MSN, ANP-BC/GNP
Mary Kirkland Center for Lupus Care, Hospital for Special Surgery
Rheumatoid arthritis (RA) is an autoimmune disease wherein the immune system attacks parts of the body leading to inflammation of the joints. While the exact cause of RA is still a mystery, it is believed that an infection can confuse the immune system causing it to start attacking the joints. Scientists think that two chemicals in our body, specifically the tumor necrosis factor (TNF) and interleukin-1 trigger the immune system in rheumatoid arthritis. Symptoms such as pain, stiffness and swelling in multiple joints of the hands, wrists, knees, feet, shoulders, can develop gradually or come on suddenly. RA symptoms are very similar to a number of other diseases, and therefore correct diagnosis even through clinical examination, x-rays, and lab tests can prove difficult. Without early treatment, the disease can damage the fibrous connective joint’s tissues, which eventually damages the bones.
There are different types of rheumatoid arthritis and understanding what type of RA you have, will help decide the course of treatment. The diagnosis of the type of RA depends on your symptoms and the clinical results of laboratory tests and x-rays. Types of RA can be differentiated by the presence or absence of an autoantibody or protein produced by the body when it starts attacking the immune system, referred to as the rheumatoid factor (RF). You can have RA without a positive RF result but its presence helps indicate the type of disease present in the body. Studies have shown that over 80% of people with rheumatoid arthritis test positive for rheumatoid factor, which is called the positive (or seropositive) rheumatoid arthritis. Sometimes patients with rheumatoid arthritis consistently have a negative test for rheumatoid factor and this milder form of rheumatoid arthritis is known as the negative (or seronegative) rheumatoid arthritis.
Rheumatoid Factor Positive (Seropositive) RA
If your blood tests positive for the presence of protein called rheumatoid factor (RF), it indicates that your body may be producing an immune reaction to your normal tissues. The RF is usually directed in sites where other antibodies are present. The presence of anti-cyclic citrullinated peptides (anti-CCPs) or anti-citrullinated protein antibodies (ACPAs) in the body along with physical symptoms of RA in the patient confirm an RA diagnosis. When proteins in the body are changing its molecular structure, there are Anti-CCPs found in the body. They are found in approximately 60 to 80% of people diagnosed with RA and the presence of these antibodies may be an early indicator of the start of RA. Antibodies can even show up in the blood tests before any clinical symptoms by about 5 to 10 years. The RF antibody can be present in patients with other medical conditions, including infection, and the anti-CCP test is more specific for RA. You are over four times more likely to develop RA, if you have first-degree relatives who have tested positive for RF.
Rheumatoid Factor Negative (Seronegative) RA
People who test negative for the presence of antibodies or RF in the blood are referred to as seronegative. But they can still have RA. Diagnosis cannot be just based on this test, as clinical symptoms, X-rays, and other laboratory tests will be taken into account. While there is no certainty of this, people who test RF negative are likely to have a milder form of RA than those who test positive.
There are some other differences that manifest in patients with seropositive and seronegative RA patients that test seropositive, or anti-CCP-positive, have a common sequence of amino acids, also known as the shared epitope, encoded in the HLA genetic site. This human leukocyte antigen locus produces proteins to control immune responses. While current research has not yet uncovered how the amino acid sequence contributes to RA, but it is through to attach to parts of proteins called citrullinated peptides, promoting the production of anti-CCP antibodies. Studies have also linked smoking to the development of RA in patients with this shared amino acid epitope. Inflammation in the lungs from smoking causes protein citrullination which produces anti-CCP antibodies in genetically susceptible people with the shared epitope.
There are differences in the risk factors associated with seropositive and seronegative disease. Anti-CCP-negative RA does not always indicate a milder form of RA disease. And while it is unlikely for a person with seronegative RA to ever turn positive, it may be an eventual indicator of a different disease altogether, like psoriatic arthritis, gout or osteoarthritis.
Autoimmune diseases tend to display many common symptoms, making their diagnosis particularly difficult. And people who are diagnosed with one autoimmune disorder may eventually develop another. Symptoms for conditions like lupus, fibromyalgia, Lyme disease, chronic fatigue syndrome, neuropathy, sciatica, anemia, hypothyroidism, and depression have overlapping symptoms. RA may even be confused with osteoarthritis, which is not even an autoimmune disorder, but is caused by daily wear and tear of the joints.
The Illinois Bone & Joint Institute has more than 90 orthopedic physicians, and 20 locations throughout Chicago. We’re here to help you move better so you can live better.
What is meant by Seronegative Arthritis?
History of the complaint, blood tests and imaging (X-rays/scans) are the basic diagnosis of any disease. “Seropositive/ Seronegative” is a term that refers to the results of a blood test.
The question is does Seronegative rheumatoid arthritis exist?
A quick answer to this is YES. When a person tests negative for rheumatoid factor also known as RF and cyclic citrullinated peptides (CCP) and is a condition that is defined by painful and swollen joints that occurs with age.
Being seronegative means, you don’t have the anti-CCPs in your blood at all or not many of them. If you, however, get a negative test for anti-CCPs and have RA symptoms then chances of being seronegative RA are higher.
The basic difference between People with seropositive RA and seronegative kind is usually the seropositive people have more pain and they are also more likely to:
- Have nodules (swollen lumps under the skin)
- Have vasculitis (inflamed blood vessels)
- Have rheumatoid lung issues
- Have other illnesses along with their RA, like cardiovascular disease.
- Smokers are at a high risk to get seropositive RA
Here’s a flowchart to show the classification of Arthritis-
Source- Doctors Gates
It generally happens when the lining of your joints attacks one’s body immune system, this is most common among middle-aged women.
The term Seronegative is derived from the fact that a blood test that does not find an indicator to detect and results in a failed blood test where no RF and anti CCPs are found in the person’s blood, these are the antibodies which are formed by the persons immune system which help attack the healthy tissues in our body
However, unlike other negative results, a seronegative arthritis result can mean a positive diagnosis for something else which is dangerous.
If we look at the chunk of people suffering from arthritis, results have found that almost 71%-80% of patients which show RS symptoms are Seropositive rheumatoid arthritis.
In the case of RA, early diagnosis is very important, the average time between the onset of symptoms and diagnosis is 6-9Months, if the RA, however, goes untreated for 2 years there is a high possibility of people developing joint erosion, indicating disease progression.
The symptoms and course of RA may vary from person to person and can also change daily, but may include:
Source- Genentech, 2016
The patients who in turn depict seronegative results are unclear of their symptoms.
Key differences between people that are seropositive and seronegative?
There is have a higher chance of developing a more serious disease in a Seropositive patient, as they are also more likely to have extra-articular complications (such as nodules and vacuities, swelling) than those patients who are seronegative.
Source- Medical Net, 2010
However, being seropositive or seronegative does not the efficiency of most of the medicines.
During the first six months of illness approximately half of RA patients are seronegative
However, study suggests that after 2 years of illness, only 15-20% of RA patients remain seronegative for RF factor.
What are the treatments?
Irrespective of the type of RA the treatment is likely to be similar
Quoting a few below-
- An anti-inflammatory medication
- A corticosteroid medication,
- A disease-modifying antirheumatic drug
- Physical therapy
- Hot water therapy
- Occupational therapy
- Standing exercises
- Surgery being the last resort
However, an essential point to make here is that these medications won’t cure your RA. They’ll just make the symptoms easier to deal with, and slow down the growth and pain
The best news about seronegative RA or seronegative spondyloarthropathy , seronegative arthritis is that patients who have seronegative results in RF and anti-CCP testing tend to develop a less serious joint disease and have fewer complications than those with seropositive results.
Types of Seronegative arthritis –
- Ankylosing spondylitis– Low back pain and stiffness are the main causes. In severe cases, the affected joints cause severe back stiffness. Other body parts such as chest wall, heels and hips may also hurt. The symptoms in children however begin from the hips to knees and later reaching the spine.
- Reactive arthritis – There is an acute pain in the sacroiliac joint that causes pain, swelling, and inflammation of the joint. There may also be slight swelling in the fingers; however, the reactive arthritis causes weight loss, skin irritation and fever.
- Psoriatic Arthritis- Is a form of arthritis that is linked to skin troubles known as psoriasis. However, an important fact to notice here is that the severity of rash does not reflect the severity of arthritis. There is also a thickening and yellow tinge around the fingernails and toenails and joint troubles arise from the large joints such as hips and sacroiliac joints.
- Enteropathic arthritis – Is a type of arthritis that occurs in the spinal cord that also involves inflammation of the intestinal wall. This type of arthritis typically affects large joints, such as the knees, hips, ankles, and elbows. In children, the arthritis may begin before the intestinal inflammation.
The treatment has changed through the years, so has the thinking about RA in some cases. There is a hope that a better understanding of the differences between the diseases we call RA may provide insights that could eventually lead to new ways to treat and, perhaps in some cases, even prevent it.
What is meant by Seronegative Arthritis? was last modified: December 10th, 2019 by Team Dr Lal PathLabsArticle Tags: arthritis · seronegative · treatment · types Article Categories: Organ Health
Alexis Ogdie1, Mei Liu 2, Sabrina Rebello 2, Angel Cronin 2, Blessing Dube 2, Robert McLean 2, Esther Yi 3, Peter Hur 3 and Philip Mease 4, 1Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 2Corrona, LLC, Waltham, MA, 3Novartis Pharmaceuticals Corporation, East Hanover, NJ, 4Swedish Medical Center/Providence St Joseph Health, and University of Washington, Seattle, WA
Meeting: 2019 ACR/ARP Annual Meeting
Keywords: anti-CCP antibodies and Rheumatoid Factor, axial spondyloarthritis, Psoriatic arthritis, Rheumatoid arthritis (RA)
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Date: Monday, November 11, 2019
Session Title: Epidemiology & Public Health Poster II: Spondyloarthritis & Connective Tissue Disease
Session Type: Poster Session (Monday)
Session Time: 9:00AM-11:00AM
Background/Purpose: Rheumatoid arthritis (RA), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA) share many clinical features but are differentiated by key clinical and molecular characteristics. Patients with RA are often seropositive (S+) for rheumatoid factor (RF) or anti-cyclic citrullinated peptide (CCP) antibodies, whereas those with PsA or axSpA are usually seronegative (S−) for these antibodies. Limited data are available comparing patients with S+ and S− RA, and few studies have compared disease burden across patients with S+ RA, S− RA, PsA, and axSpA. We compared clinical and disease characteristics among these 4 groups in the Corrona RA and PsA/SpA Registries.
Methods: Adult patients with RA enrolled in the Corrona RA Registry and those with PsA or axSpA enrolled in the Corrona PsA/SpA Registry between March 2013 and February 2019 were included. Patients with RA must have had nonmissing RF and anti-CCP values at enrollment and were classified as S+ (RF or anti-CCP ≥ 20 U/mL) or S− (RF and anti-CCP < 20 U/mL). Patient demographics, clinical characteristics, and disease activity and patient-reported outcome (PRO) measures collected at registry enrollment were compared between patients with S+ RA vs S− RA, PsA, or axSpA using t or Wilcoxon rank-sum tests for continuous variables and χ2 or Fisher exact tests for categorical variables.
Results: A total of 4827 patients with S+ RA, 1959 with S− RA, 3001 with PsA, and 512 with axSpA were included. Patients with S− RA had a higher prevalence of comorbidities than those with S+ RA, including fibromyalgia (13.1% vs 5.9%) and depression (22.7% vs 17.6%) (Table 1). Patients with axSpA had a lower prevalence of comorbidities than those with S+ RA; there was no clear trend in prevalence of comorbidities between patients with PsA and S+ RA. Overall biologic and prednisone use were comparable between patients with S+ and S− RA, whereas patients with PsA or axSpA had more biologic use and less prednisone use than those with S+ RA (Table 2). Prior csDMARD use was higher among patients with S− RA and lower among patients with axSpA than those with S+ RA; current csDMARD use was comparable between patients with S+ and S− RA but lower among those with PsA or axSpA. Patients with S+ RA had higher swollen joint counts, ESR, and CRP levels than those with S− RA, PsA, or axSpA, and higher tender joint counts than those with PsA and axSpA (Table 3). Patients with S+ RA had a higher mean physician global assessment score than those with S− RA or PsA but lower than those with axSpA. Patients with S+ RA had a mean patient global assessment score comparable with that of patients with S− RA but lower than those with PsA or axSpA.
Conclusion: Patients with S− RA had a higher comorbidity burden but similar treatment profiles and PRO scores compared with those with S+ RA. Patients with PsA or axSpA had more biologic use and worse PRO scores than those with S+ RA. These results demonstrate the differences in disease manifestations of patients with these diseases. Further studies are needed to identify factors that differentiate these disease groups, particularly regarding therapeutic response.
Disclosure: A. Ogdie, AbbVie, 5, 8, Amgen, 2, 5, 8, BMS, 5, Celgene, 5, 8, Corrona, LLC, 5, Lilly, 5, National Psoriasis Foundation, 2, NIH/NIAMS, 2, Novartis, 2, 5, 7, Pfizer, 2, 5, Rheumatology Research Foundation, 2, Takeda, 5; M. Liu, Corrona, LLC, 3; S. Rebello, Corrona, LLC, 3; A. Cronin, Corrona, LLC, 3; B. Dube, Corrona, LLC, 3; R. McLean, Corrona, LLC, 3; E. Yi, Novartis, 3, Novartis Pharmaceuticals Corporation, 3; P. Hur, Novartis, 3, Novartis Pharmaceuticals Corporation, 3, Novartis Pharmaceuticals Corporations, 3; P. Mease, Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Genentech, Janssen, Novartis, Pfizer, Roche, UCB, 2, 5, Abbott, Amgen, Biogen Idec, BMS, Eli Lilly, Genentech, Janssen, Pfizer, UCB, 8, AbbVie, 2, 5, 8, Abbvie, 2, 5, 8, Abbvie, Amgen, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, Sun, UCB, 5, Abbvie, Amgen, Bristol Myers Squibb, Celgene, Genentech, Janssen, Lilly, Novartis, Pfizer, UCB, 8, Abbvie, Amgen, Bristol Myers Squibb, Celgene, Janssen, Lilly, Novartis, Pfizer, Sun, UCB, 2, AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Genentech, Janssen, Leo, Merck, Novartis, Pfizer and UCB., 5, 8, AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Leo, Eli Lilly, Merck, Novartis, Pfizer, Sun Pharmaceutical Industries, Inc., and UCB, 2, Abbvie, Amgen, Brsitol Myers Squibb, Boehringer Ingelheim, Celgene, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, Sun, UCB, 5, Abbvie, Amgen, Brsitol Myers Squibb, Celgene, Genentech, Janssen, Lilly, Novartis, Pfizer, UCB, 8, Abbvie, Amgen, Brsitol Myers Squibb,Celgene, Janssen, Lilly, Novartis, Pfizer, Sun, UCB, 2, Amgen, 2, 5, 6, 8, Amgen, Bristol-Myers Squibb, Celgene, Galapagos, Gilead, GSK, Janssen, Leo, Eli Lilly, Merck, Novartis, Pfizer, Sun Pharmaceutical Industries, and UCB, 5, BMS, 2, 5, 8, Boehringer Ingelheim, 2, 5, Boerhinger Ingelheim, 5, Bristol Myers Squibb, 2, 5, 8, Bristol Myers Squibb Co., 2, 5, 8, Bristol-Myers Squibb, 2, 5, 6, 8, Celgene, 2, 5, 6, 8, Celgene Corp., 2, 5, 8, CORRONA, 5, Eli Lilly, 2, 5, 8, Galapagos, 2, 5, 8, Genentech, 2, 5, 6, 8, Gilead, 2, 5, 8, Janssen, 2, 5, 6, 8, Janssen Inc, 2, 5, 8, Leo, 2, 5, 8, Lilly, 2, 5, 6, 8, Merck, 2, 5, 8, Novartis, 2, 5, 6, 8, Pfizer, 2, 5, 8, Pfizer Inc, 2, 5, 6, Sun, 2, 5, SUN, 2, 5, Sun Pharma, 2, 5, Sun Pharmaceutical Industries, 2, 5, Sun Pharmaceutical Industries, Inc., 2, 5, 8, UCB, 2, 5, 6, 8, UCB Pharma, 2, 5, 8.
To cite this abstract in AMA style:
Ogdie A, Liu M, Rebello S, Cronin A, Dube B, McLean R, Yi E, Hur P, Mease P. Characteristics of Patients with Seropositive or Seronegative Rheumatoid Arthritis, Psoriatic Arthritis, or Axial Spondyloarthritis: Data from the US-Based Corrona Rheumatoid Arthritis and Psoriatic Arthritis/Spondyloarthritis (PsA/SpA) Registries . Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/characteristics-of-patients-with-seropositive-or-seronegative-rheumatoid-arthritis-psoriatic-arthritis-or-axial-spondyloarthritis-data-from-the-us-based-corrona-rheumatoid-arthritis-and-psoriatic-a/. Accessed February 2, 2020. Favorite Save to PDF
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