Development of rheumatoid factor research through 50 years

Area of Science:

• Immunology
• Rheumatology
• Autoimmunity

Background:

• Rheumatoid factors (RFs) were discovered in 1937, with consensus reached in the 1960s that they are antibodies to the Fc fragment of immunoglobulin G (IgG).
• RFs can be classified as autoantibodies (reacting with native autologous IgG), alloantibodies, or heteroantibodies.
• Cross-reacting RFs, which bind to IgG from various species or to nuclear antigens, are of significant scientific interest due to potential shared epitopes or multispecificity.

Purpose of the Study:

• To review the historical research and evolving understanding of rheumatoid factors (RFs).
• To explore the mechanisms underlying RF formation, including the role of altered IgG and immune complexes.
• To discuss the implications of RFs in the pathogenesis of diseases, particularly rheumatoid arthritis and nephropathies.

Main Methods:

• Historical literature review of RF research since the 1930s.
• Analysis of experimental studies on RF elicitation by altered IgG and immune complexes.
• Examination of recent findings on RFs in disease pathogenesis and immune complex deposition.

Main Results:

• RFs are antibodies to the Fc fragment of IgG, with specificities ranging from autologous to cross-species.
• RF formation can be induced by altered IgG, immune complexes, microbial Fc receptors, and polyclonal B cell stimulation.
• RFs are implicated in the pathogenicity of rheumatoid arthritis and can contribute to glomerular deposits in nephropathies through self-polymerization.

Conclusions:

• Understanding RFs has evolved from basic antibody identification to complex roles in autoimmunity and disease.
• Multiple factors, including immune complexes and microbial interactions, contribute to RF production in various conditions.
• RFs play a role in the pathogenesis of rheumatoid arthritis and other immune-mediated diseases, highlighting their clinical significance.