Rheumatology

What is Rheumatoid Factor?

 

Discover more about the role of rheumatoid factor in rheumatoid arthritis

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What is Rheumatoid Factor?

The Role of Rheumatoid Factor in Rheumatoid Arthritis

Rheumatoid factors are autoantibodies that react 
with the fragment crystallisable (Fc) region of immunoglobulin G (IgG) antibodies1,2

In rheumatoid arthritis, rheumatoid factors are mainly of IgM, IgG and IgA isotypes, but IgE and IgD have also been reported.1,3–5 IgG-reactive B-cells produce rheumatoid factors with high antigen-binding affinity in patients with rheumatoid arthritis.6 

 

These rheumatoid factors can bind to the IgG’s Fc region.1,6 

 

This interaction leads to the formation of large immune complexes.4,6,7 These immune complexes are internalised by macrophages through the Fc-gamma receptor (FcɣR) and are degraded by the lysosome.4,8

RF Immune Complex

RF immune complex

Immune Complexes are Degraded by Macrophages

RF immune complexes fig. 2
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Around 70–90% of people living with rheumatoid arthritis are seropositive for rheumatoid 
factor5,9-11

Testing for rheumatoid factor is easily accessible in the clinic and can be used to support a diagnosis of rheumatoid arthritis,3,5 a chronic inflammatory joint disease which leads to various other symptoms and extra-articular organ manifestations.12,13 

 

Rheumatoid factor seropositivity is different from high rheumatoid levels. No established guidelines define what are high rheumatoid factor levels and different trials use different cut-off values defining high rheumatoid factor levels.10,11,14–17 

 

Around one in four patients with rheumatoid arthritis have high rheumatoid factor levels of above 200 IU/ml.15–17

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Rheumatoid factor, especially at high levels, is considered a poor prognostic factor in rheumatoid arthritis18–20

 

Patients with rheumatoid arthritis and high rheumatoid factor levels are more inclined to experience:

Worse outcomes icon

Worse outcomes18-21

Higher disease activity

Higher disease activity21

Low rates of remission

Low rates of remission21

More aggresive disease

More aggressive disease and higher risk of radiographic progression21–23

Higher prevalence

Higher prevalence of extra-articular manifestations,22,24 associated with unfavourable outcomes for joint destruction and disability25

Increased risk of cardiovascular disease-related mortality

Increased risk of cardiovascular 
disease-related mortality26

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Discover the latest data on rheumatoid factor and its impact on rheumatoid arthritis clinical management

 

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Abbreviations

EU: European Union; Fc: fragment crystallisable; FcγR: Fc-gamma receptor; Ig: immunoglobulin; RF: rheumatoid factor; SpA: spondyloarthritis; US: United States.

References

  1. Maibom-Thomsen SL, et al. PLoS One. 2019;14(6):e0217624; 
  2. Kanmert D, et al. Scand J Immunol. 2012;75(1):115–9; 
  3. van Delft MAM, Huizinga TWJ. J Autoimmun. 2020;110:102392; 
  4. Levy RA, et al. Immunotherapy. 2016;8(12):1427–36; 
  5. Ingegnoli F, et al. Dis Markers. 2013;35(6):727–34; 
  6. Nicolò A, et al. Front Immunol. 2022;13:1016263; 
  7. Lamers MC. Allergy. 1981;36(8):527–35; 
  8. Junker F, et al. Front Immunol. 2020;11:1393; 
  9. Wu CY, et al. Int J Mol Sci. 2021;22(2):686; 
  10. Nielsen SF, et al. BMJ. 2012;345:e5244; 
  11. Smolen JS, et al. Ann Rheum Dis. 2009;68(6):797–804; 
  12. Sparks JA. Ann Intern Med. 2019;170(1):ITC1–ITC16; 
  13. Smolen JS, et al. Lancet. 2016;388(10055):2023–38; 
  14. Kratz A, et al. N Engl J Med. 2004;351(15):1548–63; 
  15. Atsumi T, et al. Ann Rheum Dis. 2016;75(1):75–83; 
  16. Smolen JS, et al. Lancet. 2016;388(10061):2763–74;
  17. Tanaka Y, et al. Int J Rheum Dis. 2023;26(7):1248–59; 
  18. Albrecht K, Zink A. Arthritis Res Ther. 2017;19(1):68; 
  19. Smolen JS, et al. Ann Rheum Dis. 2023;82(1):3–18; 
  20. Aletaha D, et al. Arthritis Rheum. 2010;62(9):2569–81; 
  21. Sobhy N, et al. Egypt Rheumatol. 2022;44(4):325–8; 
  22. van Zeben D, et al. Ann Rheum Dis. 1992;51(9):1029–35; 
  23. Vastesaeger N, et al. Rheumatology (Oxford). 2009;48(9):1114–21; 
  24. Cojocaru M, et al. Maedica (Bucur). 2010;5(4):286–91; 
  25. Nell VPK, et al. Ann Rheum Dis. 2005;64(12):1731–6; 
  26. England BR, et al. Arthritis Care Res (Hoboken). 2016;68(1):36–45.

EU-DA-2300317

 

Date of preparation: August 2024