Inflammatory Biomarker Series: Rheumatoid Factor
What are inflammatory biomarkers?
The purpose of measuring an inflammatory biomarker is to detect inflammation, which can assist clinicians in the identification of a particular disease or provide a marker of treatment response. Inflammation, either chronic or acute, is the body’s immune response to protect against harmful stimuli such as damaged cells, irritants or pathogens.1 When inflammation occurs in the body, extra protein is released from the site of inflammation and circulates in the bloodstream.2 It is these proteins, or antibodies, which clinicians are testing for in the blood as they can indicate if inflammation is present.
Like many inflammatory biomarkers, such as rheumatoid factor (RF), C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR), further tests will be required as testing for these tests alone does not provide a clearly defined diagnosis. However inflammatory biomarker tests can provide clinicians with a good indication of what may be wrong with a patient, which is why they are commonly tested for in a clinical setting.
What is Rheumatoid Factor?
Rheumatoid factor (RF) is an autoantibody which can target and damage healthy body tissue and in turn cause inflammatory symptoms.3 It is uncommon for this antibody to be present in healthy individuals, which is why it is a beneficial test to aid the diagnostic process. In particular, rheumatoid factor can be used as an inflammatory biomarker to assist in the diagnosis of rheumatoid arthritis (RA). However the rheumatoid factor antibody can also be present in healthy individuals or patients with systemic lupus erythematosus, liver cirrhosis, Sjögren’s Syndrome, Hepatitis and other conditions.4 If a test detects rheumatoid factor levels above 14 IU/ml, this is considered abnormally high.3
What is Rheumatoid Arthritis?
Rheumatoid arthritis is an autoimmune disease which attacks the lining tissue of joints, resulting in chronic inflammation. This disease commonly affects the hands, feet and wrists, with symptoms causing pain, fatigue and loss of bodily function and over time may even lead to multiple organ damage.5 Although diagnosis of rheumatoid arthritis requires a physical examination, testing for rheumatoid factor can be beneficial to assist in the diagnosis of this disease. Other blood tests that can be used to detect biomarkers associated with rheumatoid arthritis include C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), IgA, IgG, IgM and anti-cyclic citrullinated peptide (anti-CCP).
For health professionals
Randox Laboratories offer a leading portfolio of diagnostic reagents which includes a test for rheumatoid factor, with applications available for a range of biochemistry analysers. With a measuring range of 6.72 – 104 lU/ml, this assay can comfortably detect levels outside the normal range. Randox offer a complete diagnostic package for the screening of rheumatoid factor with a range of kit sizes, controls and calibrators available. Other inflammatory biomarker tests available from Randox include CRP, High Sensitivity CRP, Full Range CRP, IgA, IgG and IgM.
1. Nordqvist, C. Inflammation: Causes, Symptoms and Treatment. Medical News Today, https://goo.gl/rT4WS9 (accessed 16 January 2017)
2. Harding, M., Blood Tests to Detect Inflammation, Patient, 2015, https://goo.gl/F4OGrz, (accessed 16 January 2017)
3. Shiel, W. C., Rheumatoid Factor (RF), MedicineNet, 2016, https://goo.gl/XPA69u 2016 (accessed 16 January 2017)
4. Rheumatoid Arthritis Organisation, Rheumatoid Factor Test, Rheumatoid Arthritis Organisation, 2016, https://goo.gl/JujE5a
5. Gibofsky, A. Overview of Epidemiology, Pathophysiology and Diagnosis of Rheumatoid Arthritis. The American Journal of Managed Care. Vol.18, No.13. p.295-302, 2012
An inflammatory biomarker detects inflammation in the body. Inflammation is not just the immediate, short-term response of the body to an injury or infection. Inflammation within the body can be a long-term, chronic condition resulting in a number of health implications. In diagnostics, measurement of an inflammatory biomarker can not only detect acute inflammation but provide a marker of treatment response.
C-reactive protein (CRP) is an acute phase protein produced by the liver in response to inflammation, infection and tissue injury. CRP is a particularly beneficial inflammatory biomarker as it is detected much faster than other markers in the blood. Levels of CRP increase when inflammation occurs and therefore it can be a significant biomarker in a range of diseases, including the following.
An increasing amount of research exists to suggest CRP is not only a useful, non-specific inflammatory biomarker, but it may have a direct influence on coronary heart disease and cardiac events1. Inflammation can occur when LDL cholesterol builds up in the artery walls causing atherosclerosis. Modifiable risk factors of atherosclerosis include smoking, diabetes, poor diet, high blood pressure and physical inactivity, all factors which subsequently increase the risk of heart attacks, ischemic stroke, peripheral artery disease and even vascular dementia2,3.
Studies have also shown that persistent low levels of CRP can contribute to a person developing CVD. Therefore using high sensitivity CRP as an inflammatory biomarker can detect low levels, helping to predict the likelihood of a patient developing CVD in the future.
Research suggests that inflammation in the body can influence the development of type 2 diabetes. With the ability to be managed through diet and exercise, type 2 diabetes is commonly associated with obesity. Research has shown that excess body fat can cause continuous chronic low-grade inflammation as a result of inflammatory cytokines and increased plasma levels of CRP. As a result, this chronic inflammation has the ability to cause insulin resistance leading to the development of type 2 diabetes4.
A three year study which analysed the bone and joint health of 10,000 patient samples in India has found that inflammatory biomarkers, in particular CRP and ESR (Erythrocyte Sedimentation Rate) were raised in most of the samples compared to any other markers5. Although CRP is a non-specific inflammatory biomarker, it can be used alongside other tests, such as Rheumatoid Factor, to diagnose inflammatory joint diseases such as Rheumatoid Arthritis. Not only will CRP levels be higher due to chronic inflammation, but CRP levels can be monitored to assess levels of inflammation over time, allowing clinicians offer effective treatment.
Chronic Obstructive Pulmonary Disease (COPD)
COPD is a condition associated with inflammation of the lungs and airways. Studies have shown that measuring CRP levels is beneficial to detect exacerbations, when symptoms of COPD get suddenly worse and can last for several days. This is because CRP levels spike when exacerbations happen, causing lung function to deteriorate6.
Neonatal Bacterial Infections
CRP is one of the preferred and frequently used tests in neonatal units when diagnosing suspected bacterial infections, such as neonatal sepsis, in newborns who show signs on infection. Due to delayed synthesis during the inflammatory response, the sensitivity of CRP is lowest during early stages of infection. It is therefore critical that extremely low levels of CRP can be detected during diagnosis to distinguish whether symptoms are related to an infectious or non-infectious condition. This early detection then allows for rapid and appropriate neonatal treatment7.
Inflammatory Bowel Disease
Research suggests that using CRP as an inflammatory biomarker can help distinguish between Inflammatory Bowel Disorder (IBD) and Irritable Bowel Syndrome (IBS)8. Although IBD and IBS have some similarities in symptoms, IBD causes chronic inflammation, whereas IBS is a non-inflammatory condition. Therefore using CRP as a biomarker can allow clinicians to deliver a confident and accurate diagnosis.
For health professionals
Randox Laboratories manufacture a wide range routine and niche biochemistry reagents for use in both a research and clinical setting. With a wide measuring range, the Randox CRP assay will perform excellently to detect levels outside of the healthy range. Also available is a Full Range CRP assay particularly beneficial for use in a neonatal setting, and a High Sensitivity CRP assay, depending on your diagnostic requirements. For more information, please contact: firstname.lastname@example.org
- Shrivastava, A. K., Singh, H.V., Raizada, A. and Singh, S.K. C-reactive protein, inflammation and coronary heart disease. The Egyptian Heart Journal. 67, 89-97. (2015)
- American Heart Association. Inflammation and Heart Disease. Available from: https://goo.gl/d82Ynr (2016)
- Harvard Health Publications. What you eat can fuel or cool inflammation. Harvard Health Publications. Available from: https://goo.gl/e8m3El (2007)
- Zeyda, M. and Stulnig, T. M. Obesity, Inflammation, and Insulin Resistance – A Mini-Review. Gerontology 2009; 55:379-386 (2009)
- Mukherjeel, R. Bone and joint health are crucial aspect, usually ignored by Indians. The Times of India. Available from: https://goo.gl/qluzhI (2016)
- Anderson, G. P. COPD, asthma and C-reactive protein. European Respiratory Journal 2006; 27: 874-876. (2006)
- Hofer, N., Zacharias, E., Müller, W. and Resch, B. An update on the Use of C-Reactive Protein in Early-Onset Neonatal Sepsis: Current Insights and New Tasks. Neonatology 2012; 102: 25-36 (2012)
- Silva, P. Two Specific Proteins Allow the Exclusion of IBD in Patients with Irritable Bowel Syndrome. IBD News Today. Available from: https://goo.gl/pxMP53 (2015)