REVIEW - What happens before the onset of RA?

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Curr Opin Rheumatol. 2009 Apr 13.

What happens before the onset of rheumatoid arthritis?

Rantapää-Dahlqvist S.

Department of Rheumatology, University Hospital, Umeå, Sweden.

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.

PMID: 19365265

http://www.ncbi.nlm.nih.gov/pubmed/19365265

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