From the Guidelines
If you suspect a false positive anti-cyclic citrullinated peptide (anti-CCP) test result, the first step is to repeat the test, preferably at a different laboratory using a different assay method. This approach is crucial because false positives can occur due to laboratory errors, cross-reactivity with other antibodies, or certain conditions like hepatitis C infection, tuberculosis, or autoimmune diseases such as systemic lupus erythematosus 1. While repeating the test, it's essential to conduct a comprehensive clinical assessment, including:
- A detailed medical history
- Physical examination focusing on joints
- Additional laboratory tests like rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) Imaging studies such as X-rays or ultrasound of affected joints may also be helpful. The specificity of anti-CCP for rheumatoid arthritis is high, with a pooled specificity of .96 (95% CI 0.94–0.97) as reported in a recent study 1, indicating that a positive result is more likely to be a true positive than a false positive. However, the diagnosis of rheumatoid arthritis requires meeting established clinical criteria beyond just positive antibody tests. If the repeated anti-CCP test remains positive but clinical features are inconsistent with rheumatoid arthritis, consider consultation with a rheumatologist for expert evaluation. Persistent positivity, even without current symptoms, may indicate an increased risk for developing rheumatoid arthritis in the future and might warrant periodic follow-up 1.
From the Research
Understanding Anti-CCP False Positives
- Anti-cyclic citrullinated peptide (anti-CCP) antibodies are used for diagnosing rheumatoid arthritis (RA) due to their high specificity and sensitivity 2, 3.
- However, false-positive results can occur, and it's essential to understand the causes and implications of such results.
Causes of False-Positive Anti-CCP Results
- Anti-streptavidin IgG antibodies can interfere with anti-CCP IgG antibody assays, leading to false-positive results 4.
- Different anti-CCP assays can have varying diagnostic performances, with some assays giving more false-positive results than others 5.
- The presence of other autoimmune diseases, such as systemic lupus erythematosus (SLE) or Sjögren's syndrome, can also lead to false-positive results 2.
Diagnostic Considerations
- The anti-CCP assay has a higher specificity compared to rheumatoid factor (RF) for diagnosing RA 2, 6.
- Combining anti-CCP and RF tests can improve diagnostic accuracy and predictive value 6.
- It's crucial to consider the clinical context and other laboratory results when interpreting anti-CCP test results to minimize the risk of false positives.
Assay Variations and Interferences
- Different commercial anti-CCP assays can have varying levels of sensitivity and specificity 5.
- Interferences from anti-streptavidin IgG antibodies can be a rare but important cause of false-positive anti-CCP results 4.
- Understanding these variations and interferences is essential for accurate diagnosis and treatment of RA.