Original summary written by Lysa Petrsoric, MPH, MSW, April 20, 2015, and edited by Nancy Novick. If you have negative rheumatoid factor and negative anti-CCP and are diagnosed with rheumatoid arthritis, it is called seronegative RA. Anti-CCP and rheumatoid factor (RF) isotypes (IgM, IgA, IgG) levels were measured at entry, 12 months and again at 12 months after swapping to rituximab. We represent patients through our popular social media channels, our website CreakyJoints.org, and the 50-State Network, which includes nearly 1,500 trained volunteer patient, caregiver and healthcare activists. We believe that the most accurate information is found directly in the scientific source. If the results of both tests are negative, but a person is still showing other symptoms of arthritis, they may have seronegative. What Do the Results of an Anti-CCP Test Mean? Smoking increases the risk of testing positive for anti-CCP antibody levels and is also associated with higher levels and more severe disease status in Rheumatoid Arthritis patients [10, 11, 12, 13]. As with rheumatoid factor, some people with positive anti-CCP antibody will not have RA, but this test is somewhat more specific forRA than the rheumatoid factor. Test CCP: Cyclic Citrullinated Peptide Antibodies, IgG, Serum: Clinical and Interpretive; [cited 2020 Feb 12]; [about 2 screens]. Early detection of anti-CCP antibodies is crucial to properly treat the disease and stop its progression [10]. Atlanta: American College of Rheumatology; c2020. financial benefits of concert attendance to the community music; how many toes does a brahma chicken have; what is the difference between section 17 and section 47 https://labtestsonline.org/understanding/analytes/ccp/tab/test/, http://www.arthritisandpainclinic.com/blood-tests.html, http://arthritis.about.com/od/radiagnosis/f/anticcp.htm, http://www.webmd.com/rheumatoid-arthritis/arthritis-test-results, http://www.medicinenet.com/citrulline_antibody/index.htm, http://patient.info/doctor/rheumatoid-arthritis-pro, http://www.arthritis.org/about-arthritis/types/rheumatoid-arthritis/articles/what-type-do-you-have.php, http://rheumatology.oxfordjournals.org/content/43/5/655.full, http://ard.bmj.com/content/64/10/1521.full.pdf. The CCP (cyclic citrullinated peptide) blood test is ordered with a number of other tests to determine what an individuals rheumatoid factor happens to be. Some labs report this same result using a different measurement notation, that is, as less than 20 EU/ml.) In order to reach a rheumatoid arthritis diagnosis when a patient tests positive for anti-CCPs, several other criteria must be met. Available from: Mayo Clinic Laboratories [Internet]. Its important to note that once the RF level is elevated, it will often remain so even if the disease goes into remission. The test is ordered when a person displays signs and/or symptoms of rheumatoid arthritis. Generally, doctors combine the results of anti-CCP and rheumatoid factor tests to screen for RA. Diagnosing and managing RA involves clinical evaluation by a rheumatologist, as well as several different laboratory tests that require blood work. Vitamin D deficiency is linked to both a greater risk of developing rheumatoid arthritis and more severe arthritis symptoms such as pain, swelling, and inflammation in existing patients [15, 16]. Information is shared for educational purposes only. Le contenu de ce site Web est titre informatif uniquement et ne constitue pas un avis mdical. A positive result may also indicate that there is the . Comment * document.getElementById("comment").setAttribute( "id", "a1bed6b5b8875850fc0a432f727f48fe" );document.getElementById("a6cbe26769").setAttribute( "id", "comment" ); Save my name, email, and website in this browser for the next time I comment. 121 S. Orange Ave Orlando, FL 32801 info@rheumatoidarthritis.org 1-877-284-0235. Mayo Foundation for Medical Education and Research; c19982020. The study included 78 patients with seropositive RA (mean age, 62.31 years; 55.1% women) and evidence for anti-CCP, antimutated citrullinated vimentin (MCV), and/or RF autoantibodies. SelfDecode is a personalized health report service, Any medical information published on this website is not intended as a substitute for informed medical advice and you should not take any action before consulting with a healthcare professional. However, it isnt a very sensitive marker, which means that a negative result does not necessarily rule out rheumatoid arthritis [10]. The anti-CCP antibody test measures your bodys level of antibodies that commonly target specific proteins found in the joints. For this reason, a doctor will typically use several tests and investigations to confirm or rule out RA. Antibodies and autoantibodies are proteins made by the immune system. Remember to talk to your doctor before starting any new supplement or making significant changes to your diet. Available from: Lab Tests Online [Internet]. Around 30% of RA patients test negative for both antibodies [24]. Your provider may need to do more tests to help find out what is causing your symptoms. RASN is dedicated to providing the most up to date and trusted information. Once the diagnosis of RA has been made and confirmed, these tests are not repeated. Filed Under: Medical Articles and Infographics, 2023 HealthResearchFunding.org - Privacy Policy, 14 Hysterectomy for Fibroids Pros and Cons, 12 Pros and Cons of the Da Vinci Robotic Surgery, 14 Pros and Cons of the Cataract Surgery Multifocal Lens, 11 Pros and Cons of Monovision Cataract Surgery. Available from: Familydoctor.org [Internet]. Some people with RA may not have a positive anti-CCP test result. The anti-CCP test is thought to be slightly more specific than RF for diagnosing rheumatoid arthritis. Patients who test positive for anti-CCP antibodies at the time of diagnosis are likely to progress more rapidly and develop more destructive forms of RA [13, 26, 11]. A seropositive result could mean an overall more severe disease course than rheumatoid arthritis patients who are classified as seronegative. This will allow your doctor to detect whether anti-CCP is present in your body. A dip in anti-CCP levels tells doctors that the body has slowed down production of those inflammatory autoantibodies, and the patient might have low disease activity or be in remission. Other testing is performed to help exclude the possibility that lupus could be causing the bothersome symptoms instead of rheumatoid arthritis. Anti-CCP Antibody Test: Results and What They Mean Leawood (KS): American Academy of Family Physicians; c2020. On the other hand, the CCP test is more than 90 percent specific, which means that less than 10 percent of people who test positive donotmeet the criteria for rheumatoid arthritis. If a patient tests positive for anti-CCP, it doesnt immediately lead to a rheumatoid arthritis diagnosis. I was just diagnosed with RA. If both are positive, it is likely that a person has RA or is at risk of developing it. It can be a symptom of rheumatoid arthritis. A plus sign next to the number [1+, 2+, etc] means that the information is found within the full scientific study rather than the abstract. Anti-CCP antibody testing usually requires that you have your blood drawn and sent to a lab. The Anti-CCP Blood Test Normal Range is lower than 20 u/mL. If you test positive for anti-CCP and are diagnosed with RA, your doctor will likely pursue a more aggressive treatment regimen. SelfDecode is a personalized health report service, He is the author of numerous health-related books and contributor to several medicine, health and wellbeing websites. Negative results may not necessarily mean the lack of a disease or disorder either. A patient with rheumatoid arthritis who has positive blood tests for anti-CCP has what is commonly referred to as seropositive rheumatoid arthritis. A Mayo prospective clinical evaluation of the CCP antibody test showed a diagnostic sensitivity for RA of 78% with fewer than 5% false positive results in healthy controls (see Cautions). Natural Factors That May Decrease Inflammation in Joint Disease Align your health hacks with your genes for optimal health & cognitive function. Is anti-CCP the same as rheumatoid factor? Anti-cyclic citrullinated peptide (CCP) is an auto-antibody. Anti-CCP antibody blood tests ("strongly positive" at - NRAS Negative levels do not exclude the disease, and positive levels do not guarantee the diagnosis. Anything over this level means that you test positive for the antibodies and anything below means you test negative . If you feel that any of our content is inaccurate, out-of-date, or otherwise questionable, please leave a comment or contact us at support@selfdecode.com. 2013 May-Jun [cited 2020 Feb 12]; 29(3):773-77. ; 2018 Oct 27 [cited 2020 Feb 12]; [about 3 screens]. They are present in the majority of patients with rheumatoid arthritis. If you have suggestive signs of rheumatoid arthritis and positive results in the anti-CCP test but negative results in the RA test, or if you are symptomatic with weak results in both tests, it is likely that you are in the early phase of the disease or that it will develop in the future. These tests are slightly less accurate than tests that require blood draws that are then sent away to a lab for analysis. Rheumatoid Arthritis; [updated 2018 Aug 28; cited 2020 Feb 12]; [about 3 screens]. It is worth noting that not all patients with low levels of anti-CCP mean that the result is positive. A positive result for cyclic citrullinated peptide (CCP) antibodies indicates a high likelihood of rheumatoid arthritis (RA). A negative result by itself does not rule out the disease. A complete metabolic panel is used to monitor kidney and liver function, in order to assesswhether changes to medicationmust be made orwhether they are working well. The results of these tests may be used in two ways: The doctor and healthcare team use the results of these tests to guide treatment options for each patient. Only a medical provider has the ability to interpret what specific results may mean from this blood test based on an individuals medical history or answer specific health questions. Frustrated by the lack of good information and tools, Joe decided to embark on a learning journey to decode his DNA and track his biomarkers in search of better health. Available from: Arthritis Foundation [Internet]. Doctors use the anti-CCP antibody test in combination with other tests and symptoms to diagnose rheumatoid arthritis and determine the likely course of the disease. In addition to improving symptoms and preventing and reducing joint damage, these medications can reduce anti-CCP levels substantially [30, 31, 4]. Anti CCP Blood Test Results Meaning - HRF This may also occur in the feet, knees, hip,s elbows, shoulder, or the neck. anti ccp levels 500 - sky-cover.co.uk The presence of rheumatoid factor in the blood is not specific to RA but may indicate an autoimmune disease. Joe Cohen flipped the script on conventional and alternative medicineand it worked. Anti-CCP test results can occasionally be misleading. This test looks for CCP (cyclic citrullinated peptide) antibodies in the blood. Anti-CCP-positive patients with RA have a higher 10-year probability of Rheumatoid Arthritis (RA); 2019 Feb [cited 2020 Feb 12]; [about 2 screens]. Rheumatoid arthritis can be difficult to diagnose, especially in its early stages. Anti-CCPs have shown to be present in patients with other connective tissue disorders like systemic lupus erythematosus (SLE). Around 60% to 80% of people diagnosed with RA have anti-CCPs. After the needle is inserted, a small amount of blood will be collected into a test tube or vial. Rheumatoid arthritis - Diagnosis - NHS It is fairly common to have a general feeling of not being well if rheumatoid arthritis is present as well. Synovial fluid levels of anti-cyclic citrullinated peptide antibodies Both ESR and C-reactive protein are non-RA-specific measures of inflammation. CCP antibodies, also called anti-CCP antibodies, are a type of antibody called autoantibodies. These antibodies can be detected in as little as 3 months in individuals who have developed a high rheumatoid factor. A positive outlook depends on early detection of symptoms followed by a diagnosis. A level above 20 suggests the possibility of RA. Learn more here. A positive anti-CCP result typically indicates a person has RA, particularly if they also test positive for rheumatoid factor. Positive CCP antibodies and negative RF, it may mean you are in the early stages of rheumatoid arthritis or will develop it in the future. 3 out of 4 people who are affected by RA fit into this specific demographic. Orlando (FL): Rheumatoid Arthritis Support Network; RA and Anti-CCP: What is the Purpose of an Anti-CCP Test? (Autoantibodies develop in response to the bodys own tissue, and are characteristic of autoimmune diseases, such as RA.) In some cases, positive anti-CCP is an indication of other conditions aside from rheumatoid arthritis. Anticyclic Citrullinated Protein Antibodies Are Implicated in the I'm 29, I was diagnosed with RA about. Laboratory tests provide important information in the diagnosis, management and treatment of rheumatoid arthritis. A blood sample is drawn from the patient and analyzed in a lab. Frustrated by the lack of good information and tools, Joe decided to embark on a learning journey to decode his DNA and track his biomarkers in search of better health. The information on this website has not been evaluated by the Food & Drug Administration or any other medical body. Understanding rheumatoid arthritis lab tests and results. Special Instructions Connective Tissue Disease Cascade For high CCP positive patients, 61.9% had a diagnosis of RA. Anti-CCP antibodies can be detected in RA patients years before they show any symptoms [19, 20]. The mean level of anti-CCP antibodies declined by 131 U/ml during the 3 year follow up (95% CI 34 to 228 U/ml). 7 - 500 U/ml. If you have symptoms of rheumatoid arthritis, and your results show: Learn more about laboratory tests, reference ranges, and understanding results. Antibodies are proteins the immune system makes to fight infections, but auto-antibodies trigger autoimmunity, where the immune system attacks a persons own body. Last month, they upped my mtx to 8 tablets due to swollen hands. is a clickable link to peer-reviewed scientific studies. Available from: Lab Tests Online [Internet]. Gum disease (periodontal disease) is often caused by an infection by the bacteria P. gingivalis [3]. The positive predictive value of RA in patients with a high positive CCP 3.1 was 2.5-fold higher than those with a low positive CCP 3.1 ( P < .0001). Testing for anti-CCP antibodies helps doctors to diagnose RA patients and determine how severe the disease is, as well as predict the likely outcome of the disease. The reason for this is RF is present in patients without rheumatoid arthritis who have other autoimmune disorders. Rheumatoid factor: Ranges, tests, and treatment - Medical News Today A positive anti-CCP usually means that you have rheumatoid arthritis. Regarding the relationship between anti-CCP level and fracture risk, only the risk of major fracture was higher in group II than in group I (p = 0.005) (Fig. There is very little risk to having a blood test. Many studies have shown that CCP antibodies provide a more accurate diagnosis of rheumatoid arthritis compared with RF testing. laboratory tests, reference ranges, and understanding results, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3809312, https://www.rheumatology.org/Learning-Center/Glossary/ArticleType/ArticleView/ArticleID/439, https://www.arthritis.org/diseases/rheumatoid-arthritis, https://my.clevelandclinic.org/health/diseases/4924-rheumatoid-arthritis/diagnosis-and-tests, https://familydoctor.org/condition/rheumatoid-arthritis, https://www.hss.edu/conditions_understanding-rheumatoid-arthritis-lab-tests-results.asp, https://labtestsonline.org/tests/autoantibodies, https://labtestsonline.org/tests/cyclic-citrullinated-peptide-antibody, https://labtestsonline.org/glossary/inflammation, https://labtestsonline.org/tests/rheumatoid-factor-rf, https://www.mayoclinic.org/diseases-conditions/rheumatoid-arthritis/diagnosis-treatment/drc-20353653, https://www.mayocliniclabs.com/test-catalog/Clinical+and+Interpretive/84182, https://www.merckmanuals.com/home/bone,-joint,-and-muscle-disorders/joint-disorders/rheumatoid-arthritis-ra, https://www.nhlbi.nih.gov/health-topics/blood-tests, https://www.rheumatoidarthritis.org/ra/diagnosis/anti-ccp, https://www.urmc.rochester.edu/encyclopedia/content.aspx?contenttypeid=167&contentid=ccp, U.S. Department of Health and Human Services, Joint stiffness, especially in the morning. Vitamin D deficiency is linked to both rheumatoid arthritis and higher anti-CCP antibodies. Anti-CCP Purpose, Procedure, Result And More | Lab Tests Guide While a high CCP may mean a possibly aggressive disease course, it must be looked at with the amount of swelling, inflammation in the blood, and the number of joints involved. However, in 2010, the American College of Rheumatology changed their criteria for diagnosing RA to include the presence of anti-CCP antibodies [9]. Higher levels of antibodies to P. gingivalis are linked to higher levels of citrulline [3]. If your CCP antibody results were positive, it means these antibodies were found in your blood. Washington D.C.: American Association for Clinical Chemistry; c20012020. In addition to improving symptoms and preventing and reducing joint damage, these medications can reduce anti-CCP levels substantially [30, 31, 4]. 2023 HealthCheckUp.com. Most patients with rheumatoid arthritis have anti-cyclic citrullinated peptide (anti-CCP). It is hypothesized that the lung inflammation caused by smoking could possibly lead to developing the anti-CCP antibodies in patients who possess this shared epitope. Even though the anti-CCP is considered fairly specific for rheumatoid arthritis, you can see it sometimes in a small percentage of patients with other types of inflammatory arthritis, says Dr. Kaplan. This could happen in the earlier stages of the disease when the test is less likely to be accurate and anti-CCP levels are lower. Again, this is referring to the seronegative rheumatoid arthritis group. Early detection can help patients to maintain their quality of life and prevent the severe progression of rheumatoid arthritis. Research has shown that rheumatoid arthritis patients who test positive for anti-CCP could potentially experience a more aggressive set of symptoms and more severe damage to the affected joints. SelfDecode has the strictest sourcing guidelines in the health industry and we almost exclusively link to medically peer-reviewed studies, usually on PubMed. Cyclic Citrullinated Peptide Antibody; [updated 2019 Dec 24; cited 2020 Feb 12]; [about 2 screens]. High anti-CCP, pain in hands, feet linked to increased risk for However, auto-antibodies are proteins that cause the immune system to. This usually takes less than five minutes. The RASN is a non-profit team of healthcare professionals, and RA warriors who are committed to helping people with rheumatoid arthritis live full, happy lives despite their diagnosis. My recent one was 776 and someone on HU had a result of 1200. Omega-3s reduced inflammation in people with high anti-CCP, but more studies are needed. This is how RA develops, which means people with the condition typically have anti-CCP in their blood. You must consult your doctor before acting on any content on this website, especially if you are pregnant, nursing, taking medication, or have a medical condition. Below are the normal measurements in our lab other labs may well have their own set of normal values. Some labs report this sameresultusing a different measurement notation, that is, asless than 20EU/ml.) Anti-cyclic citrullinated peptide (anti-CCP) antibodies are commonly found in patients with rheumatoid arthritis (RA), an autoimmune disorder that destroys the joints throughout the body [1]. Available from: Cleveland Clinic [Internet]. Some researchers believe that the shared epitope is what attaches to these proteins and produces the anti-CCP antibodies. Washington D.C.: American Association for Clinical Chemistry; c20012020. SelfDecode does not treat, diagnose or cure any conditions, Supporting A Spouse With Psoriatic Arthritis. While RA is a lifelong disease, diagnosing it early and treating it properly will give the best chance at controlling its progression and allowing you to live a healthy and active lifestyle. Today, SelfDecode has helped over 100,000 people understand how to get healthier using their DNA and labs. Heres what it can and cant tell you about your disease: Anti-cyclic citrullinated peptides (anti-CCP) are a type of autoantibody: an antibody that worksagainstyour bodys normal antibodies. Rheumatoid arthritis causes inflammation due to the abnormal attack of the joints by the immune system, which supposedly protects the body from harmful foreign substances like viruses and bacteria. Anti-CCP antibodies are commonly found in rheumatoid arthritis patients and are thought to play a key role in the disease process. We suggest a new adjustment of cutoff levels for positive anti-CCP results to be lower than the current cutoff level, since we now understand the possibility of underdiagnosing 11% of additional overt RA . but is for informational and educational purposes alone. C-reactive protein is a measure of clinical inflammation often used in addition to an ESR. Available from: Lab Tests Online [Internet]. Most recommended products are used daily by our team and paid for with our personal money. Anti-CCPs are key players in the inflammatory and proatherogenic status of RA patients. We are dedicated to providing the most scientifically valid, unbiased, and comprehensive information on any given topic. Fingerstick tests give you results within 10 minutes, allowing your doctor to give you immediate feedback [21]. New York: Hospital for Special Surgery; c2019. It is common to experience higher levels of fatigue and a fever. Therefore, a positive anti-CCP alone may not confirm RA. These include: You may also need this test if other tests couldn't confirm or rule out a diagnosis of rheumatoid arthritis. Understanding Seronegative RA | Arthritis Foundation This test can be used as a prognostic tool to know whether or not the symptoms are already severe. A negative result means no CCP antibodies were found. Low Level (Below Cutoff) of Anti-Cyclic Citrullinated Peptide Test The anti-CCP does not give any indication of disease activity. For example, there are some other diseases that may cause elevated anti-CCP levels, which could confuse the interpretation of the results. Ongoing testing can help a medical provider determine how effective a treatment plan is performing. Available from: Merck Manual Consumer Version [Internet]. The typical level of anti-CCP in the blood is less than 20 endotoxin units per milliliter (EU/mL). For this reason, only a medical provider will be able to interpret individualized test results and compare them with symptoms to determine a diagnosis. Joe Cohen flipped the script on conventional and alternative medicine and it worked. That's because a positive test result can mean that another autoimmune condition besides rheumatoid arthritis may be present. Joe Cohen flipped the script on conventional and alternative medicineand it worked. The basis for determining the positive or negative anti-CCP result is 20 u/mL. In these cases, your doctor will need to factor in the severity of your symptoms, CRP and ESR, and imaging tests [27]. Cyclic Citrullinated Peptide Antibodies, IgG, Serum Useful For Evaluating patients suspected of having rheumatoid arthritis (RA) Differentiating RA from other inflammatory arthritis or connective tissue diseases Testing Algorithm For more information see Connective Tissue Disease Cascade. Samples with anti-CCP concentrations above the measuring range were diluted 1:2 to 1:5 The normal level of anti-CCP is less than 20 Units. To make a conclusive diagnosis, your doctor will take into account both of your antibody results in combination with CRP and ESR tests and any symptoms you have [25]. Anything over this level means that you test positive for the antibodies and anything below means you test negative [8]. The information on this website has not been evaluated by the Food & Drug Administration or any other medical body. Some evidence also suggests that testing positive for anti-CCP antibodies may be predictive of more aggressive disease than people who dont test positive or who test positive only for rheumatoid factor, though research in this area is ongoing. The levels of antibodies will fluctuate over time if a positive test result is received. If you also test positive for RF, you likely have the disease [25]. 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. Although lab results may vary slightly from person to person, a positive result for CCP antibodies typically means that there is a very good chance that rheumatoid arthritis is present. The prognosis of anti-CCP positive patients also depends greatly on early diagnosis of rheumatoid arthritis as well as early initiation oftreatment. Through this personalized approach, he discovered his genetic weaknesses and was able to optimize his health 10X better than he ever thought was possible. If the anti-CCP test comes back positive, a rheumatologist can likely rule out types of inflammatory arthritis that are considered to be seronegative, such as psoriatic arthritis and ankylosing spondylitis, says Dr. Kaplan. However, the anti-CCP antibody test is the most widely-used ACPA test in clinical practice due to its accuracy [5]. However, auto-antibodies are proteins that cause the immune system to attack healthy tissues. Some research suggests that oral bacteria such as P. gingivalis directly contribute to the development of rheumatoid arthritis [9]. If anti-CCP is negative, though, a person may still have RA or be in the early stages of the condition. Anti-CCP assays have a sensitivity of 39-94% (mean 64%) in patients with established rheumatoid arthritis, with a specificity of 89-98% (mean 94%). Last medically reviewed on April 11, 2023, Doctors use a combination of blood tests to help them diagnose rheumatoid arthritis. Anti-CCP is commonly produced when you have rheumatoid arthritis. Sedimentation rate (also known as erythrocyte sedimentation rate or ESR), is a crude measure of inflammation. 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). Early detection allows for an aggressive treatment plan to be created so that the bothersome symptoms can be minimized, as can the potential for tissue damage. About 70% of RA patients test positive for anti-CCP antibodies [4, 23]. Until recently, rheumatoid factor (another antibody involved in RA) was the only antibody used to help diagnose the disease. Rheumatoid Factor (RF); [updated 2020 Jan 13; cited 2020 Feb 12]; [about 2 screens]. Rheumatoid factor - Mayo Clinic Is the ketogenic diet right for autoimmune conditions? Anti-CCP is commonly produced when you have rheumatoid arthritis. Rheumatoid arthritis is not just a pain in your joints. High anti-cyclic citrullinated peptide levels and pain in the hands or feet indicate an increased risk for progression to inflammatory arthritis, especially rheumatoid arthritis, according to data . These are done to check for other potential health issues, especially anemia and signs of inflammation, that are common with individuals who have rheumatoid arthritis. Testing for the presence of anti-CCP is a relatively new support tool in helping doctors diagnose rheumatoid arthritis. Doctor, author and fitness enthusiast, Ahmed Zayed, MD, is a surgery resident with a passion for helping people live a happy healthy life. The presence of anti-CCP in a persons blood may indicate they have rheumatoid arthritis (RA). What is being detected with this test are the antibodies that are associated with the immune system response to the peptides. At 20u/mL and higher, an anti-CCP test is considered positive and, with other symptoms and factors, is usually a sign of rheumatoid arthritis.
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