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Reference Guide
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Anti-Collagen II
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Anti-Collagen II

Anti-Collagen II is an autoantibody that targets collagen type II, a protein found in cartilage that provides structural support to joints. This biomarker is primarily associated with autoimmune arthritic conditions.

Understanding the significance of Anti-Collagen II can help clinicians diagnose autoimmune arthritis early, potentially reducing the severity of irreversible joint damage and guiding personalized treatment.

What is Anti-Collagen II?

Collagen type II plays an essential role in maintaining the structural integrity of cartilage, particularly in the joints. When the immune system mistakenly targets this protein, it leads to inflammation and irreversible damage to the cartilage. 

This process occurs in autoimmune arthritis, especially rheumatoid arthritis, with Anti-Collagen II acting as a disease biomarker. For example, positive anti-collagen II testing is associated with active inflammation in the early stages of rheumatoid arthritis.

Anti-collagen II antibodies have been associated with a more aggressive, erosive form of rheumatoid arthritis, potentially indicating a distinct subgroup with rapid disease progression and joint damage.

Anti-Collagen II as an Early-Stage Biomarker of Autoimmune Arthritis

In the early stages of rheumatoid arthritis (RA), Anti-Collagen II testing is useful for detecting active inflammation, guiding treatment decisions, and predicting a favorable prognosis. 

However, its utility diminishes in later stages of the disease, as levels tend to decrease over time, making it less reliable for long-term monitoring or predicting disease outcomes.

Early detection of Anti-Collagen II can provide valuable insights into disease progression, especially in autoimmune conditions like RA.

Who Should Get Tested for Anti-Collagen II?

The following individuals may consider Anti-Collagen II testing:

Early-Stage Autoimmune Arthritis Patients, or Those With Suspected Autoimmune Arthritis 

Anti-Collagen II testing is ideal for patients with early-stage autoimmune arthritis or those with suspected autoimmune conditions, particularly those presenting systemic symptoms like fatigue, fever, skin rashes, and joint pain. 

Additionally, at-risk populations, such as those with a family history of autoimmune diseases or persistent joint symptoms after an injury or infection, may benefit from testing, especially if symptomatic.

Early identification and treatment of this pathological condition may prevent or reduce the severity of irreversible joint damage.

Test Procedure and Interpretation

The following section introduces the test procedure and interpretation.

Testing Procedure and Preparation Requirements

Anti-collagen II testing is typically performed through enzyme-linked immunosorbent assay (ELISA) or immunoblotting techniques. These tests require a blood sample drawn from an arm vein. 

No special preparation is needed before the test, though clinicians should inform patients about the purpose of the test and ask relevant questions about their symptoms and any current medications that might influence the results.

Normal Reference Ranges

The reference range for Anti-Collagen II can vary depending on the laboratory and the specific assay used. Typically, negative results are considered very low or absent, with positive results indicating levels above this threshold. 

Clinicians should always refer to the laboratory's reference range for accurate interpretation.

Clinical Implications of Elevated Levels

Elevated Anti-Collagen II levels suggest active autoimmune destruction of cartilage and are commonly linked to early-stage or aggressive RA. 

Elevated levels may also indicate an increased risk of joint damage and disability, necessitating prompt treatment to prevent further complications.

Clinical Implications of Decreased Levels

Decreased or absent levels of Anti-Collagen II cannot rule out autoimmune arthritis or other causes of joint pain. For patients with negative results, clinicians should consider other testing such as anti-CCP antibodies and rheumatoid factor for rheumatoid arthritis, as well as imaging and any other appropriate testing. 

It's essential to consider the patient’s complete clinical picture and use additional diagnostic tools.

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See References

Chauhan K, Jandu JS, Brent LH, et al. Rheumatoid Arthritis. [Updated 2023 May 25]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK441999/

Demoruelle, M. K., & Deane, K. D. (2012). Treatment strategies in early rheumatoid arthritis and prevention of rheumatoid arthritis. Current rheumatology reports, 14(5), 472–480. https://doi.org/10.1007/s11926-012-0275-1

Manviel, VA, et al. (2016). Anticollagen type II antibodies are associated with an acute onset rheumatoid arthritis phenotype and prognosticate lower degree of inflammation during 5 years follow-up . Bmj.com. https://ard.bmj.com/content/76/9/1529

Mullazehi, M., Wick, M. C., Klareskog, L., van Vollenhoven, R., & Rönnelid, J. (2012). Anti-type II collagen antibodies are associated with early radiographic destruction in rheumatoid arthritis. Arthritis research & therapy, 14(3), R100. https://doi.org/10.1186/ar3825

Raza, K., Mullazehi, M., Salmon, M., Buckley, C. D., & Rönnelid, J. (2008). Anti-collagen type II antibodies in patients with very early synovitis. Annals of the rheumatic diseases, 67(9), 1354–1355. https://doi.org/10.1136/ard.2007.084277

Townes, A. S. (1984). Autoantibodies to Type II Collagen. Mayo Clinic Proceedings, 59(11-12), 791–792. https://doi.org/10.1016/s0025-6196(12)65592-x

Type II collagen - Knowledge and References | Taylor & Francis. (2021). Taylor & Francis. https://taylorandfrancis.com/knowledge/Medicine_and_healthcare/Physiology/Type_II_collagen/

Wooley, P. H. (2015). Immunotherapy in Collagen-Induced Arthritis: Past, Present, and Future. The American Journal of the Medical Sciences, 327(4), 217–226. https://doi.org/10.1097/00000441-200404000-00008

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