Introduction of CCP Antibodies
(June 2005)
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Introduction of CCP Antibodies.pdf)
Antibodies against Cyclic Citrullinated Peptide as a marker of Rheumatoid Arthritis
Anti-Cyclic Citrullinated Peptide (Anti-CCP) antibodies are very suggestive of a diagnosis of Rheumatoid Arthritis (RA) although their absence does not exclude this diagnosis. Anti-CCP antibodies carry a higher predictive value than Rheumatoid Factor for:
- Diagnosis of RA
- Disease activity
- Radiologic damage
There is increasing evidence that patients with RA benefit from early introduction of effective disease modifying anti-rheumatic drug (DMARD) therapy. Patient selection is important to provide treatment to patients who have the most to gain from therapy, especially if commenced early in the course of the disease before bony erosions develop. However, when a patient presents with arthritis of recent onset, a definite diagnosis of the underlying pathology is very difficult.
Rheumatoid Factor (RF) is an antibody (classically IgM) to self-immunoglobulin. Presence of RF in serum from a patient with suspected RA increases the likelihood of the diagnosis of RA. Of patients with RA, those with RF positivity tend to have more aggressive arthritis than those without RF.
In 1998 Schellekens explained that historical markers for RA, such as anti-perinuclear antibodies, anti-keratin antibodies, and anti-filaggrin antibodies all bound peptides containing citrulline. Since then there have been ongoing refinements to enable these peptides to be used as the substrate of an Enzyme-Linked Immuno-Sorbent Assay (ELISA).
Clinical Utility of CCP Antibodies
Undifferentiated Arthritis
Anti-CCP antibodies have the highest positive predictive value of any single current laboratory marker for the diagnosis of RA.
Rheumatoid Factor or anti-CCP antibodies may be present prior to the onset of arthritis (particularly anti-CCP antibodies). With established RA more patients will become positive over time. This leads to a higher prevalence of anti-CCP and/or RF in patients who have established RA, and in patients that have been referred to specialist clinics. This leads to \"sensitivity" of such assays being higher in these patient groups when compared with most general practice settings. The sensitivity of anti-CCP antibodies for RA (37-66%) is only marginally better than of RF (17-71%). Therefore CCP should not be used as a screening test in patients unlikely to have RA.
Anti-CCP antibodies cannot be used to exclude a diagnosis of RA. In patients in whom inflammatory arthritis is likely, the presence of anti-CCP antibodies is highly specific (90-98%) for a diagnosis of RA, and consideration for DMARD therapy is important.
Some RA patients who are RF negative are positive for anti-CCP (up to one third in one series).
Anti-CCP antibodies are associated with a higher likelihood of radiologically evident joint damage, especially when RF is also present. The additional value of anti-CCP testing to other disease markers (radiology, RF) is relatively less in established RA than early RA.
Other Conditions
Some Juvenile Inflammatory Arthritis (JIA) patients are anti-CCP positive, but at a lower prevalence than in adult RA, and the role of anti-CCP for JIA is not as well defined. One series of Sjogren's syndrome (SS) patients were positive for anti-CCP in 8% (>60% of SS cases have RF), but 90% of these fulfilled ACR criteria for RA (and so were likely to have RA with secondary SS).
Anti-CCP passivity has been noted in other conditions (gout, osteoarthritis, sarcoid, psoriatic arthritis) in some series, but at low prevalence (<10% of cases). Some of these patients may develop clinically evident RA in the future.
Patients with Polymyalgia Rheumatica (PMR) are usually anti-CCP negative.
Combination Approach
A combination of markers has been shown to provide more clinical information than single tests. Markers that have been shown to have some predictive power include: Erythrocyte Sedimentation Rate (ESR), anti-CCP, C Reactive Protein (CRP), and RF.
The Hunter Area Pathology Service is pleased to offer testing for anti-CCP antibodies. The assay will provide a quantitative value in arbitrary ELISA units (EU).
| Reference range: |
< 20 EU |
| Weak positive: |
20-39 EU |
| Moderate positive: |
40-59 EU |
| Strong positive: |
>60 EU |
| Specimen required: |
Serum |
| Laboratory testing frequency: |
Weekly |
About the Authors
This HAPS Communique was written by Dr Theo de Malmance (Registrar), Dr Glenn Reeves (Clinical Staff Specialist), Professor Robert Clancy (Director), and Karla Lemmert (Unit Supervisor) Immunology.
If you have any questions regarding this topic Immunology can be contacted on Telephone: (02) 49214018, Facsimile: (02) 49214196.