Rheumatoid factor (RF) is the general term used to describe an autoantibody directed against antigenic determinants on the Fc fragment of immunoglobulin G. RF may be of any isotype: IgM, IgG, IgA, or IgE.
RF has a sensitivity in RA of 50% to 80%, with specificity from 80% to 90%. RA patients who are RF positive tend to have more aggressive joint disease and are at increased risk to develop extraarticular manifestations.
RF can be positive in normal individuals but usually at low titer (<50 International Units, <1:160). Males and females are affected equally. Age affects the frequency of a positive RF in normal individuals with 2% to 4% (20 to 60 years old), 5% (60 to 70 years) and 10% to 25% (>70 years) positive at low titers.
The common denominator for the production of RF is chronic immune stimulation. The most common diseases associated with RF production are (CHRONIC):
- CH Chronic disease, especially hepatic (PBC [45% to 70%]) and pulmonary diseases (IPF [10% to 50%], silicosis [30% to 50%], asbestosis [30%])
- R Rheumatoid arthritis, 50% to 85% of patients
- O Other rheumatic diseases, such as SLE (15% to 35%), systemic sclerosis (20% to 30%), MCTD (50% to 60%), Sjögren’s syndrome (75% to 95%), polymyositis (5% to 10%), sarcoidosis (15%)
- N Neoplasms, especially after radiation or chemotherapy (5% to 25%)
- I Infections (e.g., AIDS, mononucleosis, parasitic infections) (20% to 90%), chronic viral infections (15% to 65%), hepatitis B/C (20% to 75%), chronic bacterial infections [subacute bacterial endocarditis (25% to 50%), syphilis (5% to 13%), others, mycobacterial infections (TB [8%], leprosy [5% to 58%])
- C Cryoglobulinemia, 40% to 100% of patients especially with hepatitis C