What happens before the onset of rheumatoid arthritis?

Curr Opin Rheumatol. 2009 May;21(3):272-8. doi: 10.1097/BOR.0b013e32832a2e44.


Purpose of review: To give an overview of publications on presence of autoantibodies, rheumatoid factor and anticitrullinated protein/peptide antibodies (ACPAs) and their relationships to genetic markers and soluble factors as indicators of immune activation and identified predating the onset of symptoms of rheumatoid arthritis (RA).

Recent findings: The development during recent years concerning autoantibodies with high specificity for RA, ACPAs, has confirmed previous findings of presence of autoantibodies, such as rheumatoid factors and antikeratin antibodies, years before disease onset. Particularly, ACPAs in combination with human leukocyte antigen-shared epitope alleles and PTPN22 1858T carriage increased the relative risks of developing RA compared with not having these factors. Both shared epitope alleles and 1858T variant seemed to contribute to development of ACPAs rather than independently contribute to RA. Soluble factors such as hypersensitive C-reactive protein, cytokines, cytokine receptors and chemokines are upregulated before disease onset, though, not as long antedating time as ACPAs and rheumatoid factors.

Summary: Presence of ACPAs and rheumatoid factors are present several years before disease onset suggesting a gradual process leading to the development of RA. Genetic markers such as shared epitope alleles and PTPN22 1858T variant increase the relative risk for disease development. Soluble immunological markers are also increased closer to the onset of symptoms indicating activation of the immune system.

Publication types

  • Review

MeSH terms

  • Alleles
  • Antibodies, Viral / blood
  • Arthritis, Rheumatoid / etiology*
  • Arthritis, Rheumatoid / genetics
  • Arthritis, Rheumatoid / immunology
  • Autoantibodies / blood
  • Autoantibodies / genetics
  • Epitopes / genetics
  • Genetic Markers
  • Humans
  • Models, Biological
  • Peptides, Cyclic / immunology
  • Polymorphism, Single Nucleotide
  • Protein Tyrosine Phosphatase, Non-Receptor Type 22 / genetics
  • Rheumatoid Factor / blood


  • Antibodies, Viral
  • Autoantibodies
  • Epitopes
  • Genetic Markers
  • Peptides, Cyclic
  • cyclic citrullinated peptide
  • Rheumatoid Factor
  • PTPN22 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 22