Lab result explainedInflammationLast updated November 10, 2026

Anti-CCP test: normal range, what a high anti-CCP means and how it compares with rheumatoid factor

Anti-CCP antibodies (Anti-CCP) · Anti-CCP IgG (usually ordered with rheumatoid factor, CRP and ESR) · reported in U/mL (some assays report RU/mL or AU/mL); interpretation is by multiples of the laboratory's upper limit of normal

Anti-CCP antibodies, short for antibodies to cyclic citrullinated peptide and also called ACPA (anti-citrullinated protein antibodies), are the most specific blood test for rheumatoid arthritis. They target proteins in which the amino acid arginine has been chemically converted to citrulline, a change that happens in inflamed joints, in smokers' lungs and in gum tissue infected with certain bacteria. On the most widely used assays a result under about 20 U/mL is negative, though cut-offs of 5, 7 and 17 are used by others, so the reference range on your report is the one that counts.

The test's strength is its specificity. Roughly 95 percent of people with a positive anti-CCP either have rheumatoid arthritis or will develop it, compared with about 80 to 85 percent for rheumatoid factor, and the antibodies can be detected in blood samples taken up to 10 years before the first swollen joint. Its weakness is sensitivity: about 30 percent of people with rheumatoid arthritis never make these antibodies, so a negative result does not exclude the disease. Anti-CCP and rheumatoid factor are therefore ordered together and scored together in the 2010 ACR/EULAR classification criteria.

A high anti-CCP, above three times the upper limit of normal, carries prognostic as well as diagnostic weight. People with high levels develop joint erosions sooner, have more extra-articular disease (lung, nodules, vasculitis) and are the group in whom early, intensive treatment pays off most. Unlike CRP, the level does not rise and fall with day-to-day disease activity and usually stays positive on treatment, so it is a test done once or twice at diagnosis rather than repeated for monitoring.

Anti-CCP at a glance

What it is: IgG antibodies against citrullinated proteins, measured by ELISA or chemiluminescence in U/mL; the laboratory test for ACPA, the autoantibody most closely tied to rheumatoid arthritis.
Normal: below about 20 U/mL on the common second-generation (CCP2) assays; other assays use 5, 7 or 17 U/mL. Labs differ; use the cut-off on your report.
Weak positive: 20 to 39 U/mL (up to 3 times the limit); moderate 40 to 59; strong 60 U/mL and above. Anything above 3 times the upper limit is a high positive worth 3 points in the rheumatoid arthritis criteria.
Sensitivity about 67 percent, specificity about 95 percent for rheumatoid arthritis; positive in only 1 to 2 percent of healthy people.
A negative anti-CCP does not rule out rheumatoid arthritis (about 30 percent of patients are negative); a positive result with joint symptoms is close to diagnostic.
Next step: rheumatoid factor, CRP, ESR, CBC and, if you have joint pain or swelling, early rheumatology referral; if positive without symptoms, know the warning signs and be reviewed if they appear.

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What Anti-CCP measures

Citrullination is a normal chemical modification in which the enzyme peptidylarginine deiminase (PAD) converts arginine residues in proteins such as fibrinogen, vimentin, enolase and type II collagen into citrulline. It happens during inflammation and cell death, in the lungs of smokers and in gum tissue infected with Porphyromonas gingivalis, which carries its own PAD enzyme. In people with the right genetic background, chiefly the HLA-DRB1 shared epitope alleles, the immune system treats these altered proteins as foreign and makes antibodies against them. Years later, when the same citrullinated proteins appear in the lining of joints, the antibodies bind, form immune complexes, activate complement and osteoclasts, and drive the erosive arthritis.

The test does not use the body's own proteins. Laboratories coat an ELISA plate (or chemiluminescent particles) with synthetic cyclic peptides containing citrulline, chosen because their ring shape presents the citrulline the way the antibodies like to see it. Your serum is added, bound IgG is detected with a labelled anti-human antibody, and the signal is converted to units against a calibrator. Second-generation (CCP2) assays are the standard and the basis of the published sensitivity and specificity figures; CCP3 and CCP3.1 assays (which also detect IgA) are similar. Values from different manufacturers are not interchangeable, which is why reports give a cut-off and why clinicians think in multiples of the upper limit of normal.

The result is stable from day to day, unaffected by food, time of day, exercise or most medications, and does not need fasting. Methotrexate and TNF inhibitors do not usually change it; B-cell depletion with rituximab and abatacept can lower titers modestly, but conversion to negative is uncommon. A single measurement at diagnosis, with a repeat if the first result was borderline or if the clinical picture changes, is the normal pattern.

Normal range for Anti-CCP

Reference ranges vary between labs and by age, sex and pregnancy. Use the range printed on your own report.

Group	Typical range (U/mL (some assays report RU/mL or AU/mL); interpretation is by multiples of the laboratory's upper limit of normal)	Notes
Negative	Below about 20 U/mL	Common CCP2 assays use a 20 U/mL cut-off; others use 5, 7 or 17 U/mL. Use the reference range printed on your report.
Weak (low) positive	Above the cut-off up to 3 times the upper limit (about 20–60 U/mL on a 20 U/mL assay)	Scores 2 points in the 2010 ACR/EULAR criteria. Still around 90 percent specific, but a borderline value in someone without symptoms is often repeated in a few months.
Moderate positive	About 40–59 U/mL on a 20 U/mL assay	Some laboratories use this intermediate band; the ACR/EULAR criteria count only low versus high.
High (strong) positive	Above 3 times the upper limit (above about 60 U/mL on a 20 U/mL assay)	Scores 3 points. Associated with earlier erosions, more extra-articular disease and a higher chance that undifferentiated arthritis progresses to rheumatoid arthritis.
Very high	Above 250 U/mL (many assays report a maximum such as more than 250 or more than 340)	Common in established seropositive rheumatoid arthritis; the absolute number above the high-positive band adds little further prognostic information.
Healthy population	1 to 2 percent positive, usually low titer	Lower than the 5 percent false-positive rate of rheumatoid factor; prevalence rises slightly with age.
Rheumatoid arthritis	About 65 to 75 percent positive	Pooled sensitivity 67 percent, specificity 95 percent in a meta-analysis of 86 studies. About 30 percent of patients are persistently negative (seronegative RA).
Other conditions with occasional positives	Psoriatic arthritis 8–16%; palindromic rheumatism about 50%; active tuberculosis up to a third in some series; lupus and Sjögren's 5–10%	Usually low titer. Interstitial lung disease, hepatitis C and juvenile idiopathic arthritis also produce occasional positives.

High (positive) anti-CCP

A positive anti-CCP means your immune system is making antibodies against citrullinated proteins, and because these antibodies are so rarely found in people without rheumatoid arthritis, the result shifts the odds considerably. If you already have swollen joints, morning stiffness and a raised CRP or ESR, a positive anti-CCP effectively confirms rheumatoid arthritis, and a high-positive result (above three times the limit) is a signal to treat early and firmly, because this group erodes bone fastest. In the ACR/EULAR scoring, a high anti-CCP contributes 3 of the 6 points needed, so one swollen small joint plus a raised CRP and symptoms over 6 weeks completes the classification.

A positive anti-CCP without joint symptoms is a different and increasingly common finding, usually picked up on a panel ordered for vague aches or fatigue. It means you are in the pre-clinical phase that often precedes rheumatoid arthritis, in which antibodies appear a median of 3 to 5 years, and sometimes more than 10 years, before the first swollen joint. Not everyone progresses: in cohorts of anti-CCP-positive people with joint pain but no swelling, roughly 30 to 50 percent develop rheumatoid arthritis within 2 to 3 years, with high titers, a positive rheumatoid factor, a raised CRP and ultrasound-detected inflammation each raising the odds. Trials of preventive treatment (abatacept, hydroxychloroquine, methotrexate) in this group have shown delayed or reduced progression in some but not all cases, and the practical advice for now is close follow-up, stopping smoking and early treatment at the first sign of synovitis.

Low-positive results deserve a little more caution. Values just above the cut-off occur in about 1 to 2 percent of healthy people, in 8 to 16 percent of people with psoriatic arthritis, in some with lupus, Sjögren's syndrome, active tuberculosis, hepatitis C or interstitial lung disease, and transiently after some infections. If the result is borderline and the picture does not fit, it is reasonable to repeat it in 3 to 6 months and to look at the other markers before attaching the label of rheumatoid arthritis.

Common causes

Rheumatoid arthritis
The main cause by far. Positive in about two-thirds of patients, often at high titer, and present in 50 to 60 percent of people in the first months of disease. High levels predict erosions, nodules, lung disease and a poorer response to some treatments.
Pre-clinical rheumatoid arthritis
Anti-CCP can be detected up to 10 years before symptoms (in a study of blood donors who later developed RA, half were positive a median of 4.5 years beforehand). A positive result with joint pain but no swelling is called clinically suspect arthralgia and is followed closely.
Smoking
Cigarette smoke induces citrullination in the lungs and is the strongest environmental trigger of anti-CCP production. In people carrying two copies of the HLA-DRB1 shared epitope, smoking raises the risk of anti-CCP-positive rheumatoid arthritis about 20-fold.
Periodontitis
Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans in gum disease generate citrullinated proteins; periodontitis is more common and more severe in anti-CCP-positive people and may be one site where the antibodies first arise.
Psoriatic arthritis
Positive in 8 to 16 percent, usually at low titer, and associated with a more erosive, polyarticular pattern that resembles rheumatoid arthritis.
Palindromic rheumatism
Recurrent short attacks of joint swelling that resolve completely; about half of patients are anti-CCP positive and these are the ones most likely to evolve into rheumatoid arthritis.
Other autoimmune diseases
Lupus, Sjögren's syndrome, systemic sclerosis, mixed connective tissue disease and autoimmune hepatitis produce low-positive results in 5 to 10 percent, usually in those with an erosive arthritis.
Active tuberculosis and some chronic infections
Up to a third of people with active TB test positive at low titer in some series, as do a small number with hepatitis C or HIV; the result usually falls with treatment of the infection.
Interstitial lung disease
Anti-CCP is occasionally positive in people with lung fibrosis who have no arthritis, and some develop rheumatoid arthritis later; rheumatoid-associated lung disease is more common in high-titer, smoking, male patients.
Juvenile idiopathic arthritis
The polyarticular rheumatoid-factor-positive subtype in adolescents is frequently anti-CCP positive and behaves like adult rheumatoid arthritis.

Symptoms that can go with it

Often none for years; the antibodies precede symptoms, which is why a positive result without arthritis is increasingly common
Pain, swelling and warmth of the knuckles, finger joints, wrists, balls of the feet or toes, usually on both sides
Morning stiffness lasting over an hour, and stiffness after sitting still
Joint pain that comes and goes in attacks lasting hours to days (palindromic rheumatism)
Fatigue, low-grade fever, loss of appetite and mild weight loss
Firm lumps over the elbows or fingers (rheumatoid nodules) in established disease
Dry cough or breathlessness on exertion, which can indicate rheumatoid lung involvement
Bleeding or receding gums, which may accompany the periodontal disease linked to these antibodies

Read it alongside

Rheumatoid factor — ordered alongside; both positive at high titer identifies the most erosive form of rheumatoid arthritis, while RF alone is less specific.
CRP and ESR — confirm active inflammation; a positive anti-CCP with normal inflammatory markers and no swollen joints is pre-clinical rather than active disease.
Complete blood count — anemia of chronic disease and high platelets accompany active rheumatoid arthritis; baseline counts are needed before methotrexate.
ANA and ENA panel — separate lupus, Sjögren's and overlap syndromes from rheumatoid arthritis when both ANA and anti-CCP are positive.
Liver enzymes, creatinine and hepatitis B and C serology — baseline safety tests before disease-modifying drugs, and hepatitis C can itself produce low-positive results.
Uric acid — gout is a common mimic and can coexist with an incidental low-positive anti-CCP.
Hand and foot X-rays or ultrasound — erosions on X-ray or synovitis on ultrasound in an anti-CCP-positive person with joint pain predict progression and justify treatment.
Chest X-ray or high-resolution CT if there is cough or breathlessness — rheumatoid interstitial lung disease is more common in high-titer patients.

What usually happens next

If anti-CCP is positive and you have any joint swelling or morning stiffness beyond 6 weeks, ask for an early rheumatology appointment; starting a disease-modifying drug within the first 3 months of rheumatoid arthritis roughly doubles the chance of remission compared with starting a year later.
If anti-CCP is positive and you have joint pain without swelling, expect CRP, rheumatoid factor and often an ultrasound of the hands and feet; the result decides how closely you are followed and whether early treatment is discussed.
If anti-CCP is positive and you feel entirely well, the result is recorded, you stop smoking if you smoke, address gum disease, and are reviewed promptly if joints become painful or swollen; routine repeat testing is not needed.
If the result is a low positive and the clinical picture does not fit, repeat it in 3 to 6 months and check rheumatoid factor, inflammatory markers and, where relevant, tuberculosis and hepatitis C.
Do not expect the anti-CCP to be repeated to measure treatment response; it usually stays positive. Disease activity is tracked with joint counts, CRP, ESR and function scores.
If you are a first-degree relative of someone with rheumatoid arthritis and have a positive anti-CCP, mention it to your clinician; family history adds to the risk and to the case for close follow-up.

Diet, lifestyle and natural levers with evidence

What can move Anti-CCP once the cause is known. Nothing here replaces finding the cause.

Stop smoking

Strong evidence

Smoking is the one environmental factor proven to drive anti-CCP production. In the Swedish EIRA study, smokers carrying two copies of the HLA-DRB1 shared epitope had a 21-fold higher risk of anti-CCP-positive rheumatoid arthritis than non-smokers without the epitope, and a meta-analysis found current smokers had roughly double the risk of seropositive disease, with the excess fading over 15 to 20 years after quitting. In anti-CCP-positive people without arthritis, continued smoking is one of the strongest predictors of progression; in those with established disease, smokers respond less well to methotrexate and TNF inhibitors.

Treat periodontal disease

Moderate evidence

Porphyromonas gingivalis is the only bacterium known to citrullinate human proteins, and people with anti-CCP antibodies have more periodontitis and higher levels of antibodies to it. Small randomised trials of scaling and root planing in people with rheumatoid arthritis and periodontitis reduced DAS28 activity scores by around 0.5 to 1 point and lowered ESR over 6 to 12 weeks; a reduction in anti-CCP titer has been reported in some but not all studies. Regular dental care is a low-risk lever for anyone with these antibodies.

Fish oil (EPA and DHA) at high dose in early disease

Moderate evidence

In a randomised trial of 140 people with recent-onset rheumatoid arthritis treated with standard disease-modifying drugs, those taking 5.5 g a day of EPA plus DHA were twice as likely to reach remission at one year (hazard ratio 2.2) and less likely to need treatment escalation than those on a low-dose control. A separate cohort study found that regular fish oil use in anti-CCP-positive people without arthritis was associated with a lower likelihood of inflammatory arthritis. The antibodies themselves are not lowered.

Doses above 3 g a day raise bleeding risk with anticoagulants and antiplatelet drugs; discuss before combining.

Mediterranean-style diet and regular fish intake

Moderate evidence

In a Swedish cohort of over 32,000 women, eating fish at least once a week was associated with a 29 percent lower risk of developing rheumatoid arthritis, and a 12-week randomised trial of a Mediterranean diet in established disease reduced the DAS28 score by 0.56 points and improved function. The diet affects inflammation and symptoms; no diet has been shown to change anti-CCP levels.

Weight management and regular exercise

Moderate evidence

Obesity is associated with higher disease activity, a lower chance of remission and a weaker response to TNF inhibitors in rheumatoid arthritis, and in anti-CCP-positive people without arthritis a higher body mass index is one of the factors linked to progression. Meta-analyses of exercise trials show improved pain, function and fatigue without accelerating joint damage, with 2 to 3 sessions a week of aerobic or resistance training over 12 or more weeks the usual dose.

When to see a clinician promptly

A single hot, red, swollen joint with fever: possible septic arthritis, a same-day emergency regardless of antibody results.
A positive anti-CCP with any swollen joint, or with hand and foot pain and morning stiffness lasting more than 6 weeks: early rheumatology referral, because the first months are the window in which treatment prevents erosions.
A positive anti-CCP with a new dry cough or breathlessness on exertion, which can indicate interstitial lung disease and needs lung function tests and imaging.
Sudden severe neck pain with weakness, numbness or unsteadiness in someone with long-standing rheumatoid arthritis (possible instability at the top of the spine).
Red, painful eyes or sudden visual change, which can be scleritis in rheumatoid arthritis and needs prompt ophthalmology review.
Fever or signs of infection while taking methotrexate, biologics or steroids, since these treatments suppress the immune response to infection.

Frequently asked questions

What is the normal range for anti-CCP?

On the most common second-generation assays, a result under 20 U/mL is negative, 20 to 39 is weak positive, 40 to 59 moderate and 60 or above strong positive. Other manufacturers use cut-offs of 5, 7 or 17 U/mL, so the number alone can be misleading; what matters is how far above your laboratory's upper limit the result sits. Anything more than three times the upper limit is a high positive in the rheumatoid arthritis criteria.

What does a high anti-CCP mean?

A high anti-CCP, above three times the laboratory's upper limit, is about 95 percent specific for rheumatoid arthritis. With joint pain and swelling it confirms the diagnosis, and it predicts more erosive disease and more lung and nodule involvement, which is why treatment is started early and reviewed closely. Without joint symptoms it indicates a high risk of developing rheumatoid arthritis over the coming years, and the response is close follow-up, stopping smoking and prompt treatment if synovitis appears.

What is the difference between anti-CCP and rheumatoid factor?

Both are autoantibodies associated with rheumatoid arthritis and both are positive in roughly 70 percent of patients, but they are very different in specificity. Rheumatoid factor is positive in about 5 percent of healthy people, a quarter of healthy people over 70, and most people with Sjögren's syndrome or hepatitis C, giving it a specificity of around 80 to 85 percent. Anti-CCP is positive in only 1 to 2 percent of healthy people and few other conditions, giving it a specificity of about 95 percent. Having both positive at high levels is the strongest predictor of erosive disease.

Can anti-CCP be positive without rheumatoid arthritis?

Yes, in about 1 to 2 percent of healthy people and at low titer in some people with psoriatic arthritis, lupus, Sjögren's syndrome, active tuberculosis, hepatitis C or interstitial lung disease. More often, a positive anti-CCP in someone without arthritis reflects the pre-clinical phase of rheumatoid arthritis, which can last years. Roughly a third to a half of anti-CCP-positive people with joint pain but no swelling develop rheumatoid arthritis within 2 to 3 years; those who feel entirely well progress less often.

Does a negative anti-CCP rule out rheumatoid arthritis?

No. About 30 percent of people with rheumatoid arthritis never produce anti-CCP antibodies (seronegative disease), and in the earliest months of disease the figure is higher. The diagnosis in seronegative patients rests on the pattern of joint swelling, morning stiffness, raised CRP or ESR and imaging. Seronegative disease is usually less erosive but is treated with the same drugs.

Does anti-CCP go down with treatment?

Usually not much. Anti-CCP levels fall modestly in some people on methotrexate, TNF inhibitors, abatacept or rituximab, but they rarely become negative, and the level does not track day-to-day disease activity the way CRP does. For that reason the test is done at diagnosis and not repeated to monitor treatment. If your anti-CCP has fallen, that is encouraging but not the measure your clinician uses to judge control.

I have a positive anti-CCP but no symptoms. What should I do?

Three things: stop smoking if you smoke, since it is the strongest known driver of progression; keep your gums healthy; and learn the warning signs (swelling or warmth in the knuckles, wrists or toes, morning stiffness over an hour, unexplained fatigue) so you can be seen quickly if they appear. Your clinician may check rheumatoid factor, CRP and an ultrasound of your hands to refine the risk. Preventive medication is being studied but is not standard, and many anti-CCP-positive people never develop arthritis.

Do I need to fast before an anti-CCP test?

No. The result is not affected by food, time of day, exercise or most medications, and it is stable from week to week, so there is no special preparation. It is usually drawn together with rheumatoid factor, CRP, ESR and a CBC; if a lipid panel or glucose is added, those may need fasting, but the anti-CCP does not.

References

CCP antibody test. MedlinePlus, US National Library of Medicine (2023)View source
Rheumatoid arthritis: diagnosis and treatment. Mayo Clinic (2024)View source
Nishimura K, Sugiyama D, Kogata Y, et al.. Meta-analysis: diagnostic accuracy of anti-cyclic citrullinated peptide antibody and rheumatoid factor for rheumatoid arthritis. Annals of Internal Medicine (2007)
Whiting PF, Smidt N, Sterne JA, et al.. Systematic review: accuracy of anti-citrullinated peptide antibodies for diagnosing rheumatoid arthritis. Annals of Internal Medicine (2010)
Aletaha D, Neogi T, Silman AJ, et al.. 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis and Rheumatism (2010)
Rantapää-Dahlqvist S, de Jong BA, Berglin E, et al.. Antibodies against cyclic citrullinated peptide and IgA rheumatoid factor predict the development of rheumatoid arthritis. Arthritis and Rheumatism (2003)
Nielen MM, van Schaardenburg D, Reesink HW, et al.. Specific autoantibodies precede the symptoms of rheumatoid arthritis: a study of serial measurements in blood donors. Arthritis and Rheumatism (2004)
van Venrooij WJ, van Beers JJ, Pruijn GJ. Anti-CCP antibodies: the past, the present and the future. Nature Reviews Rheumatology (2011)
Källberg H, Ding B, Padyukov L, et al.. Smoking is a major preventable risk factor for rheumatoid arthritis: estimations of risks after various exposures to cigarette smoke. Annals of the Rheumatic Diseases (2011)
Proudman SM, James MJ, Spargo LD, et al.. Fish oil in recent onset rheumatoid arthritis: a randomised, double-blind controlled trial within algorithm-based drug use. Annals of the Rheumatic Diseases (2015)
Di Giuseppe D, Crippa A, Orsini N, Wolk A. Fish consumption and risk of rheumatoid arthritis: a dose-response meta-analysis. Arthritis Research and Therapy (2014)
Rheumatoid arthritis (RA). Merck Manual Professional Version (2024)

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This page is educational and is not medical advice or a diagnosis. Lab results have to be interpreted together with your history, symptoms and other results by a clinician who knows you. Do not start or stop a supplement to change a lab value before the cause is known.