Anti-CCP antibodies, or anti-citrulline antibodies, are a group of autoantibodies produced against peptides containing the amino acid L-citrulline. Anti-CCP antibodies are a highly specific marker in the diagnosis of rheumatoid arthritis and may appear even several years before the first symptoms of the disease. When to Test and How to Interpret Anti-CCP Antibody Test Results? What is the price of the test?

Anti-CCP antibodies, or anti-citrulline antibodies, are a group of autoantibodies produced against peptides containing the L-citrulline amino acid.

Citrulline peptides are produced as a result of a specific modification of proteins (citrulline), which involves the transformation of the amino acid L-arginine into another amino acid L-citrulline. Citrulination is catalyzed by peptidylarginine deaminase in the presence of a high concentration of calcium

This process takes place physiological, among others. during cell differentiation, but may also increase with tissue damage and inflammation. As a result of tissue damage, the released cell proteins, e.g. fibrin, are citrullinated.

Proteins modified in this way gain antigenic properties and can activate the immune system to produce anti-CCP (anti-CCP) antibodies of different classes.

Anti-CCP antibodies can form immune complexes with tissue proteins, which in turn activate the immune system and cause a local and systemic inflammatory response. The consequence of which may be the emergence of an autoimmune disease, such as rheumatoid arthritis.

Anti-CCP antibodies - indications for the test

The indication for the anti-CCP antibody test (very often together with the rheumatoid factor) is the suspicion of a rheumatic disease such as rheumatoid arthritis. Symptoms that may indicate a disease process include :

  • joint pain and swelling
  • morning joint stiffness that passes during the day
  • fever
  • chronic fatigue

The specificity of anti-CCP antibodies in the diagnosis of rheumatoid arthritis is very high and amounts to 95-98%. Such a high specificity of anti-CCP antibodies also allows their use in differentiationrheumatoid arthritis with other rheumatic diseases.

Therefore, according to the classification criteria published in 2010 by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR), the serological criteria for the diagnosis of rheumatoid arthritis includes, in addition to the presence of rheumatoid factor, anti-CCP antibodies.

Anti-CCP antibodies may appear many years before the first symptoms of the disease appear. Anti-CCP antibodies are found in approximately 60-70% of people in the early stages of rheumatoid arthritis.

Anti-CCP antibodies are also a recognized marker of disease activity and the severity of inflammatory changes in the tissues of the joints. In addition, in patients with rheumatoid arthritis, they are an independent unfavorable marker of erosion and progressive joint destruction.

Although anti-CCP antibodies are highly specific to rheumatoid arthritis, they may also be present in other rheumatic diseases:

  • in 44% of patients with palindromic rheumatism
  • in 9% of patients with systemic lupus
  • in 8% of patients with psoriatic arthritis
  • in 5% of patients with Sjögren's syndrome, juvenile idiopathic arthritis

and also in about 2% of he althy people.

Anti-CCP antibodies cannot be used to monitor disease activity as they tend to stay in the body for longer, even during disease remission.

Anti-CCP antibodies - price

The price of the anti-CCP antibody test, including IgG and IgA classes, is about PLN 60.

Anti-CCP antibodies - what is the test?

The anti-CCP antibody level test is performed on blood taken from the elbow bend.

The most commonly used methods for the evaluation of anti-CCP antibodies are quantitative enzyme immunoassay (ELISA, MEIA), immunofluoroenzyme (FEIA) or immunochemiluminescent (ECLIA) methods.

Currently, second and third generation tests are used, which have a higher sensitivity and specificity than the first generation tests (sensitivity 60-70% and specificity around 98%).

They use highly purified synthetic citrulline peptides, which increased the sensitivity of these tests to 80% with similar specificity as in the first generation tests. Filaggrin molecules embedded with a cyclic peptide were used in the first generation assays.

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Anti-CCP antibodies - norm, results

The reference values ​​for anti-CCP antibodies are dependent on the laboratory method used. Usually it is below 5 RU / ml, where RU stands for relative units. The result can also be expressed in U / ml.

A positive result does not always confirm, and a negative result excludes the disease. Therefore, the test result should not be interpreted in isolation from the clinical picture and other diagnostic tests.

Age and gender do not affect the level of anti-CCP antibodies in patients with rheumatoid arthritis. However, it has been shown that the concentration of anti-CCP antibodies is much higher in actively smoking patients.

If you are positive for anti-CCP (and positive for rheumatoid factor), you are likely to have rheumatoid arthritis. In addition, studies have shown that the chance of developing the disease within 5 years in he althy people with the presence of anti-CCP antibodies is 69%.

Negative for anti-CCP antibodies (and negative for rheumatoid factor) may mean a low probability of disease, but it does not exclude it. It is estimated that about 20% of people with rheumatoid arthritis are seronegative.

Worth knowing

Anti-CCP antibodies - the history of the discovery

In 1964, Nienhuis and his team discovered the presence of antibodies to the perinuclear factor (APF) in rheumatoid arthritis patients. Then, in 1979, the presence of anti-keratin antibodies (AKA) was described.

In the following years, other groups of antibodies were detected: anti-phylegrin and anti-Sa. Subsequent studies showed that all of these antibodies have in common their affinity for L-citrulline-containing peptides. Hence, they were given the collective name of anti-CCP antibodies. Other citrulline peptides described in the literature are:

  • fibrinogen α573 (Fibα573), Fibα591, Fibβ36-52, Fibβ72, Fibβ74
  • α-enolase (citrullinated α-enolase 1- CEP-1 / Eno5-21 peptide)
  • collagen type II C1 (citC1III)
  • filaggrins (CCP-1 / Fil307-324)
  • vimentyny 2-17 (Vim2-17) and Vim60-75

RA can even affect young people!

References

  1. Neogi T. et al. The 2010 American College of Rheumatology / European League Against Rheumatism classification criteria for rheumatoid arthritis. Phase 2 methodological report. Arthiritis Rheum. 2010, 62, 9, 2582-2591.
  2. Jura-PółtorakA. and Olczyk Diagnostyka K. Diagnostics and evaluation of rheumatoid arthritis activity. laboratory diagnostics Journal of Laboratory Diagnostics 2011, 47, 4, 431-438.
  3. Saigal R. et al. Seroprevalence of Anti-Citrullinated Protein Antibodies (ACPA) in Patients with Rheumatic Diseases other than Rheumatoid Arthritis. J Assoc Physicians India. 2022, 66, 4, 26-28.
  4. Basics of immunology for rheumatologists. Edited by Maśliński W. and Kontny E. Publisher of the National Institute of Geriatrics, Rheumatology and Rehabilitation prof. dr hab. med. Eleonory Reicher, Warsaw 2022.
  5. Polińska B et al. Markers of the early stage of rheumatoid arthritis. Diagn Lab 2015, 51, 4, 305-314.
About the authorKarolina Karabin, MD, PhD, molecular biologist, laboratory diagnostician, Cambridge Diagnostics Polska A biologist by profession, specializing in microbiology, and a laboratory diagnostician with over 10 years of experience in laboratory work. A graduate of the College of Molecular Medicine and a member of the Polish Society of Human Genetics. Head of research grants at the Laboratory of Molecular Diagnostics at the Department of Hematology, Oncology and Internal Diseases of the Medical University of Warsaw. She defended the title of doctor of medical sciences in the field of medical biology at the 1st Faculty of Medicine of the Medical University of Warsaw. Author of many scientific and popular science works in the field of laboratory diagnostics, molecular biology and nutrition. On a daily basis, as a specialist in the field of laboratory diagnostics, he runs the content department at Cambridge Diagnostics Polska and cooperates with a team of nutritionists at the CD Dietary Clinic. He shares his practical knowledge on diagnostics and diet therapy of diseases with specialists at conferences, training sessions, and in magazines and websites. She is particularly interested in the influence of modern lifestyle on molecular processes in the body.

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