Order Code
3505
Preferred Specimen
Collect 2 mL of serum. Allow the SST to clot in an upright position for at least 30 minutes, then centrifuge the sample within 2 hours of collection. Keep refrigerated.
Container Type:
Serum separator tube
Alternate Specimen Requirements:
Collect 2 mL of serum using a plain red-top tube. Allow the sample to clot upright for at least 60 minutes, then centrifuge and transfer the serum into a plastic transport tube within 2 hours. Clearly label the tube as serum from a plain red-top tube. Keep refrigerated.
Minimum Volume
- Adult: 0.5 mL serum
- Pediatric: 0.2 mL serum (Note: does not allow for repeat or additional testing)
Transport Temperature
Refrigerated
Expected Turnaround Time
1–2 days
Specimen Stability
After separation from cells:
Stable for 1 day at room temperature, 8 days refrigerated, and up to 3 months when frozen.
Methodology
Roche COBAS immunoturbidimetric method (WHO standard 64/2 traceable).
Rejection Criteria
Samples showing moderate or greater hemolysis are unacceptable.
Overview
Rheumatoid arthritis (RA) is a chronic autoimmune and inflammatory condition that primarily targets the synovial membranes and small joints. Without treatment, it can cause irreversible joint damage and affect multiple organs, including the skin, eyes, heart, lungs, kidneys, and nervous and gastrointestinal systems. Early diagnosis and proper management are crucial to reducing long-term complications and improving the likelihood of remission.
Rheumatoid Factor (RF) is an autoantibody directed against the Fc portion of IgG. It was the first autoantibody identified in RA and remains part of the American College of Rheumatology (ACR) diagnostic criteria. RF is mainly produced by B cells, though its exact role remains unclear. Approximately 65% to 85% of adults diagnosed with RA show positive RF results. While RF is most commonly of the IgM type, IgG and IgA variants can also occur.
Various laboratory techniques can detect RF, including particle agglutination (latex, charcoal, bentonite, or erythrocytes) and quantitative tests such as nephelometry, turbidimetry, RIA, and EIA. The classic Waaler-Rose test (sheep cell agglutination) remains in limited use. A positive RF test supports the diagnostic work-up for RA, but it should be interpreted in the context of clinical findings.
Clinical Significance
Used to help diagnose and assess rheumatoid arthritis when considered alongside clinical history, imaging, and other serologic results.
Note: Positive RF results can also occur in several non-rheumatic conditions and even in healthy individuals (see Limitations).
Additional Information
Other useful laboratory tests in the evaluation of RA include:
- Cyclic Citrullinated Peptide (CCP) Antibody: Aids diagnosis and prognosis; more specific than RF.
- 14-3-3 eta Protein: Found in serum and synovial fluid; may detect early RA with higher sensitivity.
- Erythrocyte Sedimentation Rate (ESR): Helps track disease activity.
- C-Reactive Protein (CRP): Monitors inflammation and disease activity.
- Antinuclear Antibody (ANA): May be used in broader autoimmune assessment.
Interpretative Information
- Positive Results: Supportive of an RA diagnosis and helps with differential diagnosis.
- High Titers: Often linked to worse long-term outcomes.
- Concurrent CCP Positivity: Increases diagnostic specificity.
- Negative or Low Results: Do not rule out RA, especially in early disease. RF may develop later in the disease course.
Limitations
- Most RF assays primarily detect IgM antibodies.
- A positive RF result is not specific to rheumatoid arthritis.
- RF positivity can occur in 4% of young healthy adults and up to 25% of older adults without RA.
- Elevated RF levels may be seen in autoimmune, infectious, and inflammatory diseases.
- Up to 35% of confirmed RA patients may have a negative RF test (“seronegative RA”).
- This assay is not recommended for screening asymptomatic individuals.
References
- Aletaha D, Neogi T, Silman AJ, Funovits J, et al. 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum. 2010;62(9):2569-2581.20872595
- American College of Rheumatology. Rheumatoid Arthritis. Link. Updated August 2012. Accessed November 3, 2014.
- Review criteria for assessment of rheumatoid factor (Rf) in vitro diagnostic devices using enzyme-linked immunoassay (Eia), enzyme linked immunosorbent assay (Elisa), particle agglutination tests, and laser and rate nephelometry. U.S. Food and Drug Administration website. Link. Published February 21, 1997. Updated May 29, 2014. Accessed November 4, 2014.
- Rheumatoid Arthritis Laboratory Markers For Diagnosis and Prognosis. Quest Diagnostics website. Link. Published April 4, 2013. Accessed November 3, 2014.
- Shmerling RH, Delbanco TL. How useful is the rheumatoid factor? Arch Intern Med. 1992;152(12):2417-2420.1456851
- Shmerling RH. Origin and utility of measurement of rheumatoid factors. In: Post TW. ed. UpToDate. Waltham, MA: UpToDate; 2014. Link. Accessed November 3, 2014.
- Snyder MR. The role of the laboratory in the diagnosis of rheumatoid arthritis. Mayo Medical Laboratories website. Link. Published August 2011. Accessed October, 2014.
- Song YW, Kang EH. Autoantibodies in rheumatoid arthritis: rheumatoid factors and anticitrullinated protein antibodies. QJM. 2010;103(3):139-146.19926660
- Street T. Rheumatoid factor. Medscape website. Link. Updated March 17, 2014. Accessed November 3, 2014.
- Taylor PC, Maini RN. Clinically useful biologic markers in the diagnosis and assessment of outcome in rheumatoid arthritis. In: Post TW. ed. UpToDate. Waltham, MA: UpToDate; 2014. Link. Accessed November 3, 2014.
- Venables PJW, Maini RN. Diagnosis and differential diagnosis of rheumatoid arthritis. In: Post TW. ed. UpToDate. Waltham, MA: UpToDate; 2014. Link. Accessed November 3, 2014.
- Yasir QA. Hyperuricemia. Medscape website. Link. Updated September 15, 2014. Accessed October 21, 2014.
Diagnostic Role
When used alongside clinical history, imaging, and additional laboratory markers (CCP, ESR, CRP), RF testing helps diagnose RA. However, the presence of RF is not unique to rheumatoid arthritis. It may appear in 1–4% of the general population and up to 25% of older adults. Elevated levels are also common in autoimmune diseases like Sjögren’s syndrome, Felty’s syndrome, and other infections or inflammatory conditions.
Quantitative RF testing can help estimate disease activity and prognosis, as higher RF titers are linked to more severe disease, subcutaneous nodules, vasculitis, and a poorer outlook. However, serial RF measurements are not reliable for tracking disease progression.
Alias
- RA
Test Setup Days
Monday through Friday AM shift
CPT
86431 LOINC: 11572-5
Reference Range
<14 IU/ML
| UNIT CODE | UNIT CODE NAME | ANALYTE | GENDER | AGE | REFERENCE RANGE | Units of Measure |
|---|---|---|---|---|---|---|
| 3505 | RA | RA | NOT SPECIFIED | ALL | <14 | IU/ML |
| 3505 | RA | RA | MALE | ALL | <14 | IU/ML |
| 3505 | RA | RA | FEMALE | ALL | <14 | IU/ML |