Laboratory investigations - rheumatoid factor (RF)

What it is

Rheumatoid factor (RF) - an autoantibody (usually IgM) directed against the Fc portion of IgG - one of the original serological markers for rheumatoid arthritis, now interpreted alongside the more specific anti-CCP antibody
Present in ~70-80% of RA patients, but also in a substantial minority of the healthy population (more common with age) and in several other conditions - limited specificity is the key limitation

RF forms immune complexes with IgG, which can activate complement and contribute to synovial inflammation - though its exact pathogenic contribution to RA (versus simply being a marker) remains debated

Less specific than anti-CCP for RA - positive in Sjogren's syndrome (often at high titre), SLE, chronic infection (hepatitis C, infective endocarditis, TB), and a proportion of healthy older adults
RF + anti-CCP together - the combination has higher specificity for RA than either alone, and predicts more erosive disease than either antibody in isolation
RF is one of the components of the ACR/EULAR 2010 RA classification criteria, alongside anti-CCP, joint involvement pattern, acute-phase reactants, and symptom duration

A positive RF alone, without a compatible clinical joint pattern, does not establish an RA diagnosis and does not by itself warrant disease-modifying treatment - overall clinical assessment remains central

Rheumatoid arthritis, Sjogren's syndrome, chronic hepatitis C infection, infective endocarditis (immune complex-mediated), cryoglobulinaemia

Seronegative (RF-negative) RA is common and does not exclude the diagnosis - management follows the clinical picture, not serology alone

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