Specific autoantibodies

Australian Rheumatology Association (ARA), 2018 Selmi, 2016

Note: Do not order specific autoantibodies unless the patient’s clinical features are highly suggestive of an inflammatory connective tissue disease. Specialist interpretation is recommended.

Testing for specific autoantibodies must only be undertaken if the patient has a high pretest probability of a specific diagnosis. Specialist interpretation is recommended. If there is a high pretest probability of a specific diagnosis, and the patient has a positive ANA result, it may be appropriate to test for specific autoantibodies to aid in differential diagnosis. Common tests and prevalence of specific autoantibodies associated with inflammatory connective tissue diseases lists the common tests and prevalence of specific autoantibodies associated with specific inflammatory connective tissue diseases. Most of these tests have intermediate sensitivity and specificity and are of limited diagnostic utility if considered in isolation.

If a patient has a positive ANA result, but mild nonspecific symptoms (ie low pretest probability), refer to Interpretation of a positive antinuclear antibody (ANA) result in people with mild nonspecific symptoms.

If a patient has a negative ANA or low ANA titre (eg below 1:160), do not undertake further investigation for specific autoantibodies (eg to double-stranded DNA [dsDNA] or extractable nuclear antigens [ENAs]) unless there is high pretest probability of systemic lupus erythematosus (SLE) or other inflammatory connective tissue diseaseSelmi, 2016. The coincidental association of fatigue and lethargy with a low ANA titre is probably the most common reason for a misdiagnosis of SLE.

Note: Do not test for autoantibodies to double-stranded DNA (dsDNA) or extractable nuclear antigens (ENAs) in patients with a negative ANA or low ANA titre unless there is high clinical suspicion of SLE or other inflammatory connective tissue disease.

Table 1. Common tests and prevalence of specific autoantibodies associated with inflammatory connective tissue diseases[NB1] [NB2]
Test for specific autoantibody	Prevalence of specific autoantibody
dsDNA
general population	2 to 5%
people with SLE	60%
people with other inflammatory connective tissue diseases	rare
phospholipid [NB3]
general population	5%
people with SLE	30 to 50%Pons-Estel, 2017
people with other inflammatory connective tissue diseases	common in antiphospholipid syndrome [NB4]
ENAs
Ro (SS-A)
general population	1 to 2%
people with SLE	40%
people with other inflammatory connective tissue diseases	common in Sjögren syndrome
La (SS-B)
general population	less than 1%
people with SLE	15%
people with other inflammatory connective tissue diseases	common in Sjögren syndrome
Smith (Sm)
general population	less than 1%
people with SLE	10 to 50%
people with other inflammatory connective tissue diseases	rare
U₁RNP
general population	less than 1%
people with SLE	uncommon
people with other inflammatory connective tissue diseases	common in mixed connective tissue disease
Scl-70 (topoisomerase I)
general population	less than 1%
people with SLE	rare
people with other inflammatory connective tissue diseases	common in diffuse systemic sclerosis
RNA polymerase III
general population	less than 1%
people with SLE	rare
people with other inflammatory connective tissue diseases	25% in diffuse systemic sclerosis (particularly in scleroderma renal crisis)
Jo1
general population	less than 1%
people with SLE	rare
people with other inflammatory connective tissue diseases	common in antisynthetase syndrome [NB5]
centromere staining pattern
general population	less than 1%
people with SLE	rare
people with other inflammatory connective tissue diseases	common in limited systemic sclerosis
Note: dsDNA = double-stranded DNA; ENA = extractable nuclear antigen; SLE = systemic lupus erythematosus NB1: Do not test for autoantibodies to dsDNA or ENAs in people with a negative or low ANA titre unless there is high clinical suspicion of SLE or other inflammatory connective tissue disease.Australian Rheumatology Association (ARA), 2018 NB2: Investigations requested should be determined by a person’s clinical presentation. NB3: Antiphospholipid antibodies include lupus anticoagulant, anticardiolipin, and anti-beta-2-glycoprotein-1. Refer to Investigations for APS. NB4: Antiphospholipid syndrome can occur secondary to inflammatory connective tissue diseases, or as a primary syndrome. NB5: Antisynthetase syndrome is an idiopathic inflammatory myopathy associated with fever, arthralgia, severe interstitial lung disease, ‘mechanic’s hands’ and Raynaud phenomenon.