Rheumatoid Factor: The Most Remarkable Autoantibody in Rheumatoid Arthritis

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Rheumatoid Factor: The Most Remarkable Autoantibody in Rheumatoid Arthritis

12 October 2019

Rheumatoid Factor: The Most Remarkable Autoantibody in Rheumatoid Arthritis

The European League Against Rheumatism (EULAR) launched the ‘Don’t Delay, Connect Today’ campaign in 2017, continuing into 2019 for World Arthritis Day. The day is a global awareness day focusing on promoting the symptoms associated with rheumatic and musculoskeletal diseases (RMDs). Moreover, the world awareness day focuses on the importance of early diagnosis and access to care 1. Randox Reagents fully supports the importance of early diagnosis which aids in the early implementation of effective treatment plans, aiding in improved health outcomes. On this World Arthritis Day, Randox Reagents will delve deeper into rheumatoid factor (RF), the most remarkable autoantibody in rheumatoid arthritis.

Pathobiology of Rheumatoid Arthritis (RA)

Rheumatoid arthritis (RA), “the most common systemic inflammatory autoimmune disease” affecting 1% of the global population, is characterised by fatigue, synovial joint pain, stiffness, swelling and destruction, with severe symptoms resulting in disability. Whilst the exact cause of RA is unknown, it is believed that genetic and environmental factors play a role in triggering the disease 2, 3.  Differences in the human leukocyte antigen (HLA)-DRB1 alleles (proteins with a critical role in the immune system) have been identified as a genetic variant for RA, observed in >80% of patients, particularly in those testing positive for RF. Moreover, those with variations in the HLA-DRB1 who smoke, increase their risk of RA. As RA is more common in women (2-fold increased risk in women compared to men), hormonal influences are an area of active research, however, an inverse correlation with breastfeeding has been identified. Women who breastfeed for >13 months aids in reducing the risk of RA compared to women who have never breastfed 3, 4.

The pathophysiology of RA involves various signalling pathways and immune modulators (effector cells and cytokines) as indicated in figure 1. Joint destruction is caused by the intricate interactions of immune modulators, beginning at the synovial membrane and encompassing most IA structures, with synovitis caused by both or individually, the local activation or influx of mononuclear cells, including: B cells, T cells, dendritic cells, plasma cells, mast cells and macrophages. Consequently, “the synovial lining becomes hyperplastic, and the synovial membrane expands and forms villi”. The neutrophils, chondrocytes and synoviocytes secrete enzymes that degrades the cartilage in the joint whereas the osteoclast-rich area of the synovial membrane destroys the bone 4.

Figure 1: Schematic view of (a) a normal joint and (b) a joint affected by RA 4 

Clinical Significance of Rheumatoid Factor (RF)

Interestingly, elevated levels of RF have been observed in other autoimmune conditions such as Sjögren syndrome and systemic lupus erythematosus (SLE) as well as non-autoimmune conditions including old age and chronic infections. Despite this, RF in RA patients can be distinguished from RF in healthy individuals. RF in RA patients displays affinity maturation whereas RF in healthy individuals has low affinity and are polyreactive 2.

RF is a class of immunoglobulin (Ig) autoantibodies that are directed against the fragment crystallizable region (Fc region), the tail region of the IgG antibody. In RA, RF are produced by the B cells present in lymphoid follicles and the germinal center(GC)-like structures that mature in inflamed synovium. Most RF are IgM antibodies, but may also be IgG or IgA isoforms. IgM RF are detected in 60% to 80% of RA patients. “RF testing in RA patients has a sensitivity of 60% to 90% and a specificity of 85%” (5). RF is a highly valuable biomarker in RA 5, 2.

Key Features of the Randox Rheumatoid Factor Assay

The Randox automated latex enhanced immunoturbidimetric rheumatoid factor assay provides an accurate assessment of RF titre as the Randox rheumatoid factor calibrator is standardised against the primary WHO material, 1st British Standard 64/2. With a wide measuring range of 6.72 – 104lU/ml for the comfortable detection of clinically important results, the Randox RF assay is available in a liquid ready-to-use format for the comfortable detection of clinically important results. The Randox rheumatoid factor assay does not suffer from interference from C1q complement and is stable until expiry date. With dedicated calibrator and controls for a complete testing package, Randox offer applications, detailing instrument-specific settings for the convenient use of the Randox rheumatoid factor assay on a wide range of clinical chemistry analysers.

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Rheumatoid Arthritis and Women’s Health

Rheumatoid Arthritis (RA) is a chronic autoimmune disease characterised by pain, swelling and stiffness in joints which commonly affects the hands, wrists and feet.  Whilst both men and women can suffer from rheumatoid arthritis, it is more commonly seen in women than men.

Rheumatoid arthritis is the most common autoimmune disease with a higher prevalence rate compared to lupus, multiple sclerosis, type 1 diabetes, Crohn’s disease and psoriasis.

(Simmons, 2013)

The incidence rates of rheumatoid arthritis differ between men and women.  The onset of RA occurs much earlier for women, for most, during their 30’s and 40’s.  In an American study, it was noted that the incidence rates peak for women around the ages of 55 to 64, compared to 75 to 84 years of age for men.

(Simmons, 2013)

As most women are diagnosed with rheumatoid arthritis in their 30’s and 40’s, a study found that the diagnosis negatively impacts both the body and mind of women, as indicated in their pain, disease activity, and quality of life scores.  This is due to women being diagnosed at a time when their burdens are the heaviest as this is the time when women are most likely to have children or are raising children combined with work and socialising.

Changes in hormone levels also impacts women.  It has been noted that before a menstrual period, women find the symptoms of rheumatoid arthritis to be more severe, but settles during their cycle.  Also, due to the changes in hormone levels during pregnancy, 50 – 60% of women with rheumatoid arthritis noticed that their symptoms improved.

The key to managing rheumatoid arthritis is to start the treatment as early as possible as it can halt or slow the disease, preventing joint damage and complications, including: osteoporosis and cardiovascular disease.  Rheumatoid arthritis increases the risk of heart attack by 60%.  To start treatment as early as possible, it is important that it is diagnosed as early as possible.

Randox offer a number of key assays for the diagnosis of rheumatoid arthritis.

Rheumatoid factor is the most routinely run test to diagnose rheumatoid arthritis as 80% of rheumatoid arthritis patients test positive for rheumatoid factor.  The Randox Rheumatoid Factor reagent offers the following benefits:

  • Wide measuring range of 6.72 – 104lU/ml for the accurate measurement of clinically important results
  • Accurate assessment of rheumatoid factor titre (calibrant standardised against primary WHO material; 1st British Standard 64/2)
  • No interference from complement C1q
  • Automated immunoturbidimetric assay
  • Applications available for a wide range of biochemistry analysers, detailing instrument-specific settings

It has been found that complement C4 and CRP upregulation indicates the middle to late stages of rheumatoid arthritis.

The Randox Complement C4 reagent offers the following benefits:

  • Wide measuring of 3.41 – 152mg/dl for the accurate measurement of clinically significant results
  • Limited interferences from Bilirubin, Haemoglobin, Intralipids, and Triglycerides, producing more accurate results
  • Automated immunoturbidimetric assay
  • Applications available for a wide range of biochemistry analysers, detailing instrument-specific settings

The Randox High-Sensitivity CRP reagent offers the following benefits:

  • Wide measuring of 0.477 – 10mg/l fir the accurate measurement of clinically significant results
  • Liquid ready-to-use reagents for convenience and ease of use
  • Applications available for a wide range of biochemistry analysers, detailing instrument-specific settings

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.

References:

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

Inflammatory Biomarker: Rheumatoid Factor


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