What is the normal range for rheumatoid factor (RF) in International Units per milliliter (IU/mL)?

Normal Range for Rheumatoid Factor (RF)

The normal range for rheumatoid factor (RF) is less than or equal to the upper limit of normal (ULN) for the laboratory and assay, which is typically considered to be ≤14-15 IU/mL. 1

Understanding Rheumatoid Factor Values

• RF values are reported in International Units per milliliter (IU/mL) and are standardized against the WHO reference rheumatoid arthritis serum preparation 2
• According to the 2010 ACR/EULAR Classification Criteria for Rheumatoid Arthritis, RF results are categorized as follows:
  • Negative: Values less than or equal to the upper limit of normal (ULN) 1
  • Low positive: Values higher than ULN but ≤3 times ULN 1
  • High positive: Values more than 3 times ULN 1

Clinical Significance of RF Levels

• RF is one of the most characteristic laboratory parameters in rheumatoid arthritis (RA), with its specificity for the disease increasing when the titer is high 3
• Elevated RF levels are associated with increased risk of developing RA:
  • RF levels 25-50 IU/mL: 3.6-fold increased risk 4
  • RF levels 50.1-100 IU/mL: 6.0-fold increased risk 4
  • RF levels >100 IU/mL: 26-fold increased risk 4
• High RF titers (>300 IU/mL) are significantly associated with rheumatoid nodules in patients with RA 3

Interpretation Considerations

• RF is not specific to RA and can be found in other conditions:
  • Other inflammatory diseases of connective tissue 3
  • Liver diseases 3
  • Infections 3
  • Neoplasms 3
• The positive predictive value of RF for RA is relatively low (24%), while the negative predictive value is higher (89%) 5
• When RF information is only available as positive or negative (without specific values), a positive result should be scored as low positive for classification purposes 1

Laboratory Testing Considerations

• The error of the ELISA assay for RF (coefficient of variation) is generally less than 10% at both high and low concentrations 2
• Different laboratories may use different methods and reference ranges, so results should be interpreted in the context of the specific laboratory's normal range 2
• RF levels remain relatively stable across age groups from 20 to 100 years 4

Clinical Application

• RF testing is part of the 2010 ACR/EULAR Classification Criteria for RA, contributing up to 3 points in the scoring system (with 6 points needed for RA classification) 6
• RF should be interpreted alongside anti-citrullinated protein antibody (ACPA) status, as both are important serological markers for RA diagnosis and prognosis 6
• Positive RF and/or ACPA are useful predictors of severe disease and poor prognosis in patients with RA 1