Rheumatoid Factor

Rheumatoid factor (rheumatoid factor) is autoantibodies of various subclasses (IgM, IgG, IgA, IgE) directed against specific regions of the body’s class G immunoglobulins (IgG) (Fc fragment of IgG). It can be used for the diagnosis of rheumatic diseases. Rheumatic forms include (frequency of a positive rheumatoid factor):

  • Dermatomyositis (30%) – disease belonging to the collagenoses, which affects the skin and muscles and is associated mainly with diffuse movement pain.
  • Cryoglobulinemia (40-100%) – chronic recurrent immune complex vasculitides (immune disease of the vessels) characterized by the detection of abnormal cold precipitating serum proteins (cold antibodies).
  • Lupus erythematosus (10-35%) – systemic disease affecting the skin and connective tissue of the vessels, leading to vasculitides (vascular inflammation) of numerous organs such as the heart, kidneys or brain.
  • Mixed connective tissue disease (50-60%) – chronic inflammatory connective tissue disease in which symptoms of various collagenoses (systemic lupus erythematosus, scleroderma, polymyositis, Raynaud’s syndrome) occur.
  • Panarteritis nodosa (40%) – is a necrotizing vasculitis that usually affects medium-sized vessels; in this case, the inflammation involves all wall layers (pan = Greek all; arteri- from artery = arteries; -itis = inflammatory).
  • Polymyositis (30%) – is classified as a collagenosis; it is a systemic inflammatory disease of skeletal muscle with perivascular lymphocytic infiltration.
  • Progressive systemic sclerosis (30%) – see Scleroderma.
  • Rheumatoid arthritis (50-90%) – is a chronic inflammatory multisystem disease that usually manifests as synovitis (inflammation of the synovial membrane). It is also known as primary chronic polyarthritis (PcP).
  • Sharp syndrome (60%) – chronic inflammatory connective tissue disease that includes symptoms of several collagenoses such as lupus erythematosus, scleroderma or polymyositis.
  • Scleroderma (20-30%) – is included in the group of collagenoses as an “inflammatory rheumatic disease” associated with connective tissue hardening of the skin alone or of the skin and internal organs (especially digestive tract, lungs, heart, and kidneys)
  • Sjögren’s syndrome (75-95%) (group of sicca syndromes) – autoimmune disease from the group of collagenoses leading to a chronic inflammatory disease of the exocrine glands, most commonly the salivary and lacrimal glands; typical sequelae or complications of sicca syndrome are:
    • Keratoconjunctivitis sicca (dry eye syndrome) due to lack of wetting of the cornea and conjunctiva with tear fluid.
    • Increased susceptibility to caries due to xerostomia (dry mouth) due to reduced salivary secretion.
    • Rhinitis sicca (dry nasal mucous membranes), hoarseness and chronic cough irritation and impaired sexual function due to disruption of mucous gland production of the respiratory tract and genital organs.

Rheumatoid factor is also detectable in up to five percent of the healthy population. In people over 65, this percentage can increase to 20 percent. Healthy relatives of individuals with rheumatoid arthritis also have increased positive rheumatoid factor. Individuals with rheumatoid arthritis who have a high titer tend to have a more severe course of the disease.

The procedure

Material needed

  • Blood serum
  • Synovial fluid

Preparation of the patient

  • Not necessary

Disruptive factors

  • Not known

Standard values

Normal value (latex agglutination test). <30 IU/ml
Normal value (nephelometry) <37 IU/ml

Indications

  • Suspicion of diseases of the rheumatic system.

Interpretation

Interpretation of lowered values

  • Not relevant to disease

Interpretation of elevated values

  • Age > 70 (10-25%)
  • Chronic liver disease
  • EBV infection (synonyms: EBV; EBV infection; Epstein-Barr virus infection; infectious mononucleosis (glandular fever); kissing disease; mononucleosis; monocyte angina; glandular fever; student sickness).
  • Endocarditis (endocarditis).
  • Hepatitis B (liver inflammation)
  • Infections:
    • Bacterial endocarditis (25-50%).
    • Schistosomiasis – worm disease (tropical infectious disease) caused by trematodes (sucking worms) of the genus Schistosoma (couple flukes).
    • Hepatitis (15-40%)  
    • Leprosy
    • Malaria
    • Syphilis (Lues)
    • Tuberculosis (8%)
    • Viral infections (15-65%)
    • Visceral leishmaniasis (kala-azar) – infectious disease caused by parasites, the leishmania. Transmission occurs via sand or butterfly mosquitoes (phlebotomes). Visceral leishmaniasis (kala-azar) is a disease of the internal organs.
  • Pulmonary diseases
    • Asbestosis (30%)
    • Pulmonary fibrosis (10-50%)
    • Sarcoidosis (synonyms: Boeck’s disease; Schaumann-Besnier’s disease) (3-33%)
    • Silicosis (13%)
  • Lymphoma – malignant disease of the lymphatic system.
  • Primary biliary cirrhosis – form of liver cirrhosis that occurs mainly in women.
  • Rheumatoid arthritis (50-90%) or other diseases of the rheumatoid form (see above); if the rheumatoid factor is detectable, it is called seropositive rheumatoid arthritis.
  • Tumor diseases (esp. leukemias and colon carcinoma) (5-25%).
  • Condition after vaccination
  • Condition after transfusion of blood

Data in (round brackets) indicate frequency for a positive rheumatoid factor test. Further notes

  • As a basic diagnostic test, the following laboratory tests should be performed when rheumatoid arthritis is suspected.
    • CRP (C-reactive protein) or ESR (erythrocyte sedimentation rate).
    • Rheumatoid factor (or CCP-AK)
    • ANA (antinuclear antibodies)
    • HLA-B27 (Histocompatibility antigens).
  • Complaint-free people with positive rheumatoid factor or elevated rheumatoid-specific autoantibodies (ACPA) already have an increased risk of atherosclerosis. The antibodies are a sign of an overactive immune system.