Rheumatoid Factor:

The Most Remarkable Autoantibody in Rheumatoid Arthritis

Celebrating World Arthritis Day (WAD)

Rheumatoid Factor: The Most Remarkable Autoantibody in Rheumatoid Arthritis

World Arthritis Day (WAD) is celebrated on 12th October to help raise global awareness of the existence and impact of rheumatic and musculoskeletal diseases (RMDs). It is estimated that over one-hundred million people are currently undiagnosed impacting their quality of life and participation in society – including their ability to work and lead a normal life. As a result this increases dependency on state welfare, the healthcare system and the required support from their family and friends.

The European League Against Rheumatism (EULAR) launched the ‘Don’t Delay, Connect Today’ campaign focusing on the importance of early diagnosis and access to care.

Randox Reagents fully supports the importance of early diagnosis – to aid in the early implementation of effective treatment plans, aiding in improved health outcomes – it’s the ethos of our business. This blog delves deeper into rheumatoid factor (RF), the most remarkable autoantibody in rheumatoid arthritis.

Pathobiology of Rheumatoid Arthritis (RA)

The pathophysiology of RA involves various signaling 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.

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}.

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, 1^st 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.

Find out more about the Randox Rheumatoid Factor Assay

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