Rheumatoid Factor

RF is one of several indicators of autoimmunity.

IgM autoantibodies; against Fc portion of IgG

 

Measured by latex fixation: reported by dilution with >1:40 being abnormal

 

An immunoglobulin directed against the Fc portion of IgG. It can be isotype IgG, IgA or IgM. Usually it is only IgM.

 

 new test - anti-cyclic citrullinated peptide

90-96% specificity

47-76% sensitivity
 

Interpretation
A positive result is > 20 i.u. 4-20% of healthy people have a detectable R.F, with increases seen in age. 75% of patients with established Rheumatoid Arthritis have a positive R.F, but only 30% in first three months. High levels correlate with disease severity. R.F. is also seen in other chronic immune diseases such as Sjogren’s Syndrome and hepatitis C.

 

can be type II (monoclonal IgM to polyclonal IgG) or type III (polyclonal IgM to polyclonal IgG)

 

make a table; rheumatic vs non-rheumatic

• normal aging
• SLE (15-35%)
• mixed connective tissue disease
• cryoglobulinemia
• systemic vasculitis
• polymyositis, dermatomyositis, others
• sarcoidosis
• TB
• leprosy
• syphilis
• viral infections, especially hepatitis C
• hepatitis B and C, HIV
• asbestosis and idiopathic pulmonary fiibrosis
• Sjongren's disease

 

 

Antibodies are sensitive markers for SLE (over 95%), but specificity is low - are found in 3-5% of healthy people and with other diseases. If negative, the need to persue other testing is not necessary.

Can also be positive in lymphoproliferative diseaae, chronic infections, a number of drugs, and other things.

Conditions associated with a positive ANA include

• drug-induced lupus (100%)
• chronic active hepatitis (100%)
• SLE (98%)
• systemic sclerosis (95%)
• mixed connective tusse disease (95-99%)
• polymyositis/dermatomyositis (90%)
• Sjogren's syndrome (80%)
• rheumatoid arthritis (60%)
• myasthenia gravis (50%)
• diabetes (25%)

 

Protocol

Cells from a human tumor cell line are placed on a slide and coated with serial dilutions of the patient’s serum. Using fluorescein-labeled anti-human IgG to detect the bound autoantibodies, the technician reports the pattern of staining.

 

Staining Patterns are important, but have largely been replaced by extractable nuclear antigens

•  A diffuse pattern is binding across the nucleus, with antibody binding to DNA itself specificity 95%, sensitivity 30-70%.
• a peripheral pattern, staining around the nucleus is also specific for SLE.

 

 

Interpretation
A positive titer is > 1/100. 
Specific Autoantibodies
Immunoassay techniques allow detection of antibodies against cellular antigens.

Anti-Phospholipid Antibodies (APLA)

 

Anti-Phospholipid Antibodies (APLA) are directed against phospholipids and phospholipid binding proteins. These can develop in a number of settings:

• medications
• autoimmune diseases, ie SLE
• infectious diseases, ie HIV
• neoplastic disease

APS is not only based on labs; one also needs clinical features such as thrombosis or repeated miscarriage.

The two best characterized groups include anti-cardiolipid antibody (aCL) and lupus anticoagulant (LAC). LAC can interfere with PTT.

Extractable Nuclear Antigens

Antibodies against nuclear proteins occur in a number of autoimmune diseases.

 

Ro/SSA - Sjogren's syndrome, systemic lupus erythmatosus

 

La/SS - Sjogren's syndrome, systemic lupus erythmatosus

 

Sm - systemic lupus erythmatosus (low sensitivity, buy very high specificity)

RNP - systemic lupus erythmatosus, mixed connective tissue disease

 

centromere - CREST

 

anti-Scl 70 - systemic sclerosis (scleroderma)

 

anti-Jo1

inflammatory myositis