Rheumatoid Factor
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Antibodies directed against the Fc fragment of immunoglobulin G (IgG) are called rheumatoid factors (RFs). They are heterogenous and usually composed of immunoglobulin M (IgM). Because of this, most assays detect only IgM. RFs are used as a marker in individuals with suspected rheumatoid arthritis (RA) or other autoimmune conditions. [1, 2, 3, 4]
The normal reference range for RF is less than 15 IU/mL [5] or less than 1:16. [4]
Rheumatoid factor (RF) is used in the diagnosis of rheumatoid arthritis (RA). RF results are positive in approximately 75% of patients with RA, although RF is not etiologically related to RA. [6]
High RF titers indicate a poorer prognosis, as patients with higher RF levels tend to have more severe disease. Patients with nodules or clinical evidence of vasculitis usually have positive RF results.
Low levels of RF can even be found in healthy patients, and the test is positive in up to 20% of older individuals. [4]
Collection details are as follows:
Specimen type – Serum
Container/tube – Red top, gold top or tiger top preferred (gel- bottom tube best, but any serum-type tube adequate)
Specimen volume – 1 mL, 0.5 mL minimum [5]
Reject specimens in cases of gross lipemia [5]
Specimen stability – Refrigerated (preferred) 14 days, ambient 14 days, frozen 14 days
Test often included in autoimmune panels
Rheumatoid factor (RF) has historically been measured with all the following assays: Agglutination of sheep RBCs that have been sensitized with rabbit IgG, radioimmunoassays and enzyme immunoassays, and agglutination of polystyrene latex particles coated with human IgG. No assay has been proven to be better than another, and, lack of standardization between tests leads to variability in results.
Immunoglobulin M (IgM) autoantibodies against the Fc fragment of immunoglobulin G (IgG) are called rheumatoid factors (RFs). These proteins are produced by B cells and can be found circulating in the blood. Their role is unknown in both healthy individuals and in those with rheumatoid arthritis. Approximately 60-80% of individuals with rheumatoid arthritis (RA) have RF present during the course of their disease. However, RF results are positive in less than 40% of patients with early RA. RF levels vary based on disease activity, though even patients with drug-induced remissions generally retain high titers of RF.
RF is also present with other connective-tissue diseases, autoimmune disorders, and proinflammatory states. It is also observed in 1-5% of healthy individuals. Thus, RF is not considered specific for RA.
RF results may be positive in patients without RA who have the following conditions:
RA is a chronic, autoimmune, peripheral polyarthropathy of unknown etiogenesis. The diagnosis of RA is made via clinical, laboratory, and imaging features, as no test results are pathognomonic. For patients with suspected RA, the following studies are potentially useful:
Erythrocyte sedimentation rate (ESR)
C-reactive protein (CRP)
Complete blood cell (CBC) count
RF assay
Anticyclic citrullinated peptide antibody (anti-CCP) assay (currently used in the 2010 ACR/EULAR classification criteria)
False-negative and false-positive results are common in patients without RA as well as those with RA; patients without RA have an 8% rate of false results, whereas patients with RA have a 15% rate.
RF results may be positive in patients without RA who have the following conditions:
Because of its poor specificity and poor positive predictive value, RF is only one test used to diagnose RA and must be ordered judiciously and with purpose. [4]
See Rheumatoid Arthritis: In and Out of the Joint, a Critical Images slideshow, to help identify the distinguishing features of RA as well as the signs of extra-articular manifestations of this disfiguring disease.
Aletaha D, Alasti F, Smolen JS. Rheumatoid factor determines structural progression of rheumatoid arthritis dependent and independent of disease activity. Ann Rheum Dis. 2013 Jun. 72(6):875-80. [Medline].
O’Dell JR, Haire CE, Erikson N, et al. Treatment of rheumatoid arthritis with methotrexate alone, sulfasalazine and hydroxychloroquine, or a combination of all three medications. N Engl J Med. 1996 May 16. 334(20):1287-91. [Medline].
Mjaavatten MD, van der Heijde DM, Uhlig T, et al. Should anti-citrullinated protein antibody and rheumatoid factor status be reassessed during the first year of followup in recent-onset arthritis? A longitudinal study. J Rheumatol. 2011 Nov. 38(11):2336-41. [Medline].
Westwood OM, Nelson PN, Hay FC. Rheumatoid factors: what’s new?. Rheumatology (Oxford). 2006 Apr. 45(4):379-85. [Medline].
Mayo Clinic. Rheumatoid factor, serum. Mayo Medical Laboratories. Available at http://www.mayomedicallaboratories.com/test-catalog/Specimen/9060. Accessed: 9/7/12.
Heidari B, Firouzjahi A, Heidari P, Hajian K. The prevalence and diagnostic performance of anti-cyclic citrullinated peptide antibody in rheumatoid arthritis: the predictive and discriminative ability of serum antibody level in recognizing rheumatoid arthritis. Ann Saudi Med. 2009 Nov-Dec. 29(6):467-70. [Medline]. [Full Text].
Aletaha D, Alasti F, Smolen JS. Rheumatoid factor determines structural progression of rheumatoid arthritis dependent and independent of disease activity. Ann Rheum Dis. 2013 Jun. 72(6):875-80. [Medline].
Temprano KK. Rheumatoid Arthritis. Medscape Drugs & Diseases. Available at http://emedicine.medscape.com/article/331715-workup. 2012 Aug 20; Accessed: September 7, 2012.
Tyler Street, MD Resident Physician, Department of Plastic Surgery, The Warren Alpert Medical School of Brown University
Tyler Street, MD is a member of the following medical societies: Alpha Omega Alpha, American Society of Plastic Surgeons
Disclosure: Nothing to disclose.
Scott T Schmidt, MD Clinical Assistant Professor, Department of Surgery, The Warren Alpert Medical School of Brown University; Director of Hand Surgery, Assistant Program Director, Director of Microsurgical Resident Training Lab, Department of Plastic Surgery, Rhode Island Hospital
Disclosure: Nothing to disclose.
Eric B Staros, MD Associate Professor of Pathology, St Louis University School of Medicine; Director of Clinical Laboratories, Director of Cytopathology, Department of Pathology, St Louis University Hospital
Eric B Staros, MD is a member of the following medical societies: American Medical Association, American Society for Clinical Pathology, College of American Pathologists, Association for Molecular Pathology
Disclosure: Nothing to disclose.
Rheumatoid Factor
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