Medicine – Common Autoantibodies in Connective Tissue Diseases

Autoantibodies are antibodies produced by the immune system that react against the body’s own cellular components. They are important laboratory markers in connective tissue and autoimmune diseases and can help support a diagnosis, distinguish between related conditions, and, in selected diseases, provide information about disease activity or likely organ involvement. However, autoantibody results should always be interpreted together with the patient’s clinical presentation because many antibodies can occur in more than one condition.

1. Anti-dsDNA Antibodies

Anti-double-stranded DNA (anti-dsDNA) antibodies are strongly associated with systemic lupus erythematosus (SLE). They are relatively specific for SLE and therefore provide useful support for the diagnosis when the appropriate clinical features are present. Anti-dsDNA levels may also correlate with disease activity in some patients, particularly in lupus nephritis, where rising titres can accompany active renal disease.

2. Anti-Smith (Anti-Sm) Antibodies

Anti-Smith (anti-Sm) antibodies are another important marker of SLE. Although they are present in only a proportion of patients, they are highly specific for SLE, making them particularly useful diagnostically. Unlike anti-dsDNA antibodies, anti-Sm levels generally do not closely reflect changes in disease activity.

3. Anti-Ro Antibodies

Anti-Ro antibodies, also known as anti-SSA antibodies, are particularly associated with Sjögren’s syndrome and SLE. In Sjögren’s syndrome, they may occur in patients with prominent dryness of the eyes and mouth resulting from autoimmune involvement of the exocrine glands. In SLE, anti-Ro antibodies are associated with certain manifestations, particularly photosensitive skin disease. They are also clinically important during pregnancy because maternal antibodies can cross the placenta and are associated with neonatal lupus and congenital heart block.

4. Anti-La Antibodies

Anti-La antibodies, also called anti-SSB antibodies, are associated mainly with Sjögren’s syndrome and SLE. They frequently occur together with anti-Ro antibodies and can provide additional evidence of an underlying autoimmune connective tissue disease. Like anti-Ro, maternal anti-La antibodies may also be relevant when assessing the risk of neonatal autoimmune manifestations during pregnancy.

5. Anti-RNP Antibodies

Anti-ribonucleoprotein (anti-RNP) antibodies, particularly antibodies against U1-RNP, are strongly associated with mixed connective tissue disease (MCTD). This disorder combines clinical characteristics of several connective tissue diseases, including features resembling SLE, systemic sclerosis, and inflammatory myositis. Anti-RNP antibodies may also occur in SLE, but high titres in the appropriate clinical setting are particularly characteristic of mixed connective tissue disease.

6. Anti-Jo-1 Antibodies

Anti-Jo-1 antibodies are associated with inflammatory myositis, particularly polymyositis and the antisynthetase syndrome. Patients may develop proximal muscle weakness, and the presence of anti-Jo-1 is particularly associated with interstitial lung disease. Other features of the antisynthetase syndrome can include inflammatory arthritis, Raynaud phenomenon, fever, and characteristic roughened skin over the fingers known as mechanic’s hands.

7. Anti-Scl-70 Antibodies

Anti-Scl-70 antibodies, also known as anti-topoisomerase I antibodies, are particularly associated with diffuse cutaneous systemic sclerosis. This form of systemic sclerosis can produce widespread skin thickening together with internal organ involvement. Anti-Scl-70 positivity is especially associated with an increased risk of interstitial lung disease and pulmonary fibrosis.

8. Anti-Centromere Antibodies

Anti-centromere antibodies are strongly associated with limited cutaneous systemic sclerosis, historically referred to as the CREST syndrome. In this form of systemic sclerosis, skin involvement is generally more restricted than in diffuse disease. The CREST features include calcinosis, Raynaud phenomenon, oesophageal dysmotility, sclerodactyly, and telangiectasia. Anti-centromere antibodies are also associated with an increased risk of developing pulmonary arterial hypertension during the course of the disease.

9. Anti-Cardiolipin Antibodies

Anti-cardiolipin antibodies belong to the group of antiphospholipid antibodies and are associated with antiphospholipid syndrome (APS). They may also occur in patients with SLE, either with or without clinical antiphospholipid syndrome. Persistent antiphospholipid antibodies can be associated with an increased tendency toward arterial or venous thrombosis and pregnancy-related complications, such as recurrent pregnancy loss. Diagnosis of antiphospholipid syndrome requires appropriate clinical findings together with persistent laboratory evidence of antiphospholipid antibodies.

10. Anti-Histone Antibodies

Anti-histone antibodies are classically associated with drug-induced lupus. Drug-induced lupus is a lupus-like autoimmune syndrome that can develop after exposure to certain medications. Patients commonly develop constitutional symptoms, arthralgia, and other lupus-like manifestations. Anti-histone antibodies are frequently detected, although they are not completely specific because they may also occur in idiopathic SLE and other autoimmune conditions.

Important Associations to Remember

The most useful associations for revision are anti-dsDNA and anti-Sm with SLE; anti-Ro and anti-La with Sjögren’s syndrome and SLE; anti-RNP with mixed connective tissue disease; anti-Jo-1 with inflammatory myositis; anti-Scl-70 with diffuse systemic sclerosis; anti-centromere with limited systemic sclerosis; anti-cardiolipin with antiphospholipid syndrome; and anti-histone antibodies with drug-induced lupus.