Order Code
5827
Preferred Specimen
1 mL serum. Allow SST to clot in an upright position for at least 30 minutes, then centrifuge sample within 2 hours of collection. Refrigerate.
Container Type:
Serum separator tube
Alternate Specimen Requirements:
2 mL serum from a plain red top tube. Allow sample to clot in an upright position for at least 60 minutes, then centrifuge sample and transfer serum to a plastic transport tube within 2 hours of collection. Clearly label tube as serum from a plain red top tube. Refrigerate.
Minimum Volume
2 mL serum
Transport Temperature
Refrigerated
Specimen Stability
2 days room temperature; 2 weeks refrigerated; 3 months frozen
Methodology
Enzyme-linked immunosorbent assay (ELISA)
Rejection Criteria
- Gross hemolysis
- Lipemia
- Contaminated samples
- Heat-inactivated samples
Overview
Rheumatoid arthritis (RA) is a systemic, autoimmune, inflammatory disease affecting synovial membranes and multiple articular small joints. Left untreated, disease progression leads to irreversible joint damage; systemic effects include damage to skin, eyes, heart, lungs, kidneys, nervous system, and gastrointestinal system.
Early diagnosis and treatment can alleviate long-term complications and increase the chances of remission.
Rheumatoid Factor (RF) is an autoantibody produced against the Fc portion of IgG. It was the first autoantibody associated with RA and is part of the American College of Rheumatology classification criteria for RA diagnosis (ACF 2012).
RF proteins are produced by B cells, but their role remains unclear. Approximately 65%–85% of adults clinically diagnosed with RA have serologic evidence of RF. Although most commonly of the IgM class, IgG and IgA RFs can also be elevated. Detecting all three improves specificity for RA diagnosis (Quest, 2013).
IgA and IgG RFs are occasionally found in RA patients in the absence of IgM and may have prognostic value, as their presence is linked to more severe disease.
Clinical Significance
Aids in the diagnosis and prognosis of RA when used alongside clinical history, radiographic findings, and other serologic tests.
Interpretative Information
Positive Results:
- Consistent with RA; aids in differential diagnosis.
- High titers indicate poorer long-term outcomes (Song, 2010).
- Concurrent positive cyclic citrullinated peptide antibody (CCP) improves specificity for RA diagnosis.
Limitations
- A positive RF test is not specific for rheumatoid arthritis.
- Positive RF results appear in 4% of young healthy individuals and 3–25% of older patients without rheumatic disease (Shmerling, 2014).
- High RF levels can occur in autoimmune, chronic infectious, and inflammatory disorders.
- Up to 35% of RA patients have negative RF tests—so a negative result does not rule out RA.
- Female patients and those with elderly-onset RA are more likely to be seronegative.
References
- Aletaha D, Neogi T, Silman AJ, Funovits J, et al. Rheumatoid arthritis classification criteria: an ACR/EULAR collaborative initiative. Arthritis Rheum. 2010;62(9):2569–2581.
- American College of Rheumatology. Rheumatoid Arthritis. Updated August 2012.
- U.S. Food and Drug Administration. Review criteria for assessment of rheumatoid factor diagnostic devices. Updated May 29, 2014.
- Quest Diagnostics. Rheumatoid Arthritis Laboratory Markers For Diagnosis and Prognosis. April 2013.
- Shmerling RH, Delbanco TL. How useful is the rheumatoid factor? Arch Intern Med. 1992;152(12):2417–2420.
- Shmerling RH. Origin and utility of measurement of rheumatoid factors. In: Post TW. ed. UpToDate. Waltham, MA; 2014.
- Snyder MR. The role of the laboratory in the diagnosis of rheumatoid arthritis. Mayo Medical Laboratories, 2011.
- Song YW, Kang EH. Autoantibodies in rheumatoid arthritis: rheumatoid factors and anticitrullinated protein antibodies. QJM. 2010;103(3):139–146.
- Street T. Rheumatoid factor. Medscape, 2014.
- Taylor PC, Maini RN. Clinically useful biologic markers in diagnosis and outcome assessment in RA. UpToDate, 2014.
- Venables PJW, Maini RN. Diagnosis and differential diagnosis of RA. UpToDate, 2014.
- Whelan P. Clinical manifestations and diagnosis of rheumatoid vasculitis. UpToDate, 2014.
- Yasir QA. Hyperuricemia. Medscape, 2014.
Diagnostic Role
The IgM RF isotope is most commonly used for diagnosis, but detection of IgA and IgG increases specificity for RA.
- High titers of IgA RF are associated with radiologic erosion and extra-articular manifestations (Song, 2009).
- All three isotopes tend to be elevated in rheumatoid vasculitis compared to RA alone (Whelan, 2014).
When used with clinical history, radiographic studies, and other biomarkers (CCP, ESR, CRP), RF is a valuable diagnostic marker.
However, RF presence is not unique to RA—it is also found in:
- 1–4% of the general population
- Up to 25% of older adults
- Nearly all patients with Felty and Sjögren Syndromes
Increased RF titers may also accompany:
- Viral infections
- Tuberculosis
- Leprosy
- Parasitic diseases
- Liver disease
- Sarcoidosis
- Systemic lupus erythematosus
Test Setup Days
Monday, Wednesday, Friday
CPT
83516 X3