Rheumatoid Factor

Aka: Rheumatoid Factor, RF, Rheumatoid Factor Test

1. See Also
   1. Rheumatoid Arthritis
   2. Anticyclic Citrullinated Peptide Antibody
2. Mechanism
   1. Polyclonal B Cell activation synthesizes RF autoantibody
   2. RF IgM (rarely IgG) Antibody
      1. Binds IgG constant region (crystallizable fragment)
   3. Serum Detection
      1. Latex fixation
         1. Agglutination of latex particles
         2. Latex coated with human IgG
      2. Sheep Cell Agglutination Assay indications
         1. Negative latex fixation despite high suspicion
3. Causes: Negative
   1. Normal
   2. Conditions in which Rheumatoid Factor is expected to be negative
      1. Osteoarthritis
      2. Ankylosing Spondylitis
      3. Gout
      4. Chondrocalcinosis
      5. Suppurative Arthritis
      6. Psoriatic Arthritis
      7. Enteropathic Arthritis
      8. Reiter's Syndrome
4. Causes: Positive
   1. Rheumatoid Factor present in normal persons
      1. Very Low titers (<1:80) present in many patients
      2. Normally present in 1-5% of general population
      3. Incidence of RF increases with age
      4. Incidence of RF increases in age over 65 years: 10%
   2. Rheumatoid Arthritis (33-90%)
      1. RF Titer alone does not diagnose Rheumatoid Arthritis
         1. Test Sensitivity: 69%
         2. Test Specificity: 85%
         3. Positive Likelihood Ratio (LR+): 4.86
         4. Negative Likelihood Ratio (LR-): 0.38
      2. Prognosis worse with high titer at onset
         1. Higher titers are associated with erosive Arthritis, extraarticular involvement
      3. RF Incidence increases with duration of disease
         1. Three months: 33%
         2. Six months: 45%
         3. One year: 75%
         4. Eighteen months: 90%
         5. Up to 20% of RA patients remain seronegative
   3. Other Autoimmune Disease
      1. Sjogren's Syndrome (75 to 95%)
      2. Systemic Lupus Erythematosus (15 to 35%)
      3. Scleroderma (20 to 30%)
      4. Polymyositis or Dermatomyositis (10%)
      5. Cryoglobulinemia (40 to 100%)
      6. Mixed Connective Tissue Disease (50 to 60%)
   4. Infections
      1. Bacterial Endocarditis
      2. Osteomyelitis
      3. Tuberculosis
      4. Syphilis
      5. Hepatitis (Acute and Chronic)
      6. Mononucleosis
      7. Parasitic Infection
      8. Viral Infection (esp. Mumps, Rubella, Influenza)
   5. Lung Disease
      1. Asbestosis
      2. Diffuse interstitial pulmonary fibrosis
      3. Sarcoidosis
      4. Silicosis
   6. Gastrointestinal Conditions
      1. Hepatic Cirrhosis
      2. Primary biliary Cirrhosis
   7. Cancer
      1. Leukemia
      2. Colon Cancer
5. References
   1. Ali (2018) Am Fam Physician 98(3): 164-70 [PubMed]
   2. Shmerling (1991) Am J Med 91:528-34 [PubMed]
   3. Nishimura (2007) Ann Intern Med 146(11): &97-808 [PubMed]