What is the specificity of anti-centromere antibody (ACA) for systemic sclerosis (scleroderma)?

From the Guidelines

Anti-centromere antibodies are highly specific for limited cutaneous systemic sclerosis (lcSSc), with a specificity of approximately 97%, making them a valuable diagnostic marker for scleroderma. The presence of anti-centromere antibodies is associated with a better prognosis compared to other scleroderma-specific antibodies, with less severe skin involvement and a lower risk of interstitial lung disease 1. However, patients with ACA positivity have a higher risk of developing pulmonary arterial hypertension and digital ulcers over time.

Key Points

• Anti-centromere antibodies are found in approximately 70-80% of patients with limited cutaneous scleroderma but are rarely present in diffuse cutaneous systemic sclerosis (dcSSc) 1.
• The main centromere proteins targeted by these antibodies are CENP-A, CENP-B, and CENP-C, with CENP-B being the most commonly recognized antigen in clinical testing.
• Testing for anti-centromere antibodies is typically done using indirect immunofluorescence or enzyme-linked immunosorbent assay (ELISA) methods.
• The presence of anti-centromere antibodies is considered protective and decreases the likelihood of ILD development in SSc 1.

Clinical Implications

• The specificity of ACA for scleroderma makes it a valuable diagnostic marker, though it can occasionally be found in other conditions such as primary biliary cholangitis (5-30% of cases) and Sjögren's syndrome (5-10% of cases) 1.
• Patients with ACA positivity require regular monitoring for the development of pulmonary arterial hypertension and digital ulcers.
• Early detection and treatment of ILD and PAH are crucial in improving the prognosis of patients with SSc 1.

From the Research

Anti-Centromere Antibody Specificity for Scleroderma

• The anti-centromere antibody is highly specific for limited systemic sclerosis, particularly the CREST syndrome, with a prevalence of 55% in this subset of patients 2, 3.
• The antibody is rarely found in patients with rapidly advancing or diffuse scleroderma, making it a useful prognostic indicator in patients with early scleroderma 2.
• The sensitivity of anti-centromere antibodies in systemic sclerosis is around 32%, but increases to 57% in patients with limited cutaneous systemic sclerosis (lcSSc) 4.
• The specificity of anti-centromere antibodies is high, with fewer than 1% of disease-free controls having the antibody present, but 5% of patients with other connective tissue diseases may also test positive 4.
• Anti-centromere antibodies can also be detected in patients with systemic lupus erythematosus (SLE), although at a lower frequency (1.9%), and do not necessarily indicate concurrent scleroderma 3.
• The presence of anti-centromere antibodies in patients with rheumatoid arthritis (RA) and limited systemic sclerosis (lcSSc) overlap syndrome has been reported, with cross-reactivities between anti-centromere protein A (CENP-A) and anti-CENP-B antibodies with anti-A2/RA33 antigens observed in some cases 5.
• The clinical distribution of anti-centromere antibodies in scleroderma spectrum disorders (SSD) has been studied, with a frequency of 30% in SSD patients, and 67% in suspected secondary Raynaud's phenomenon and type I systemic sclerosis patients 6.