From the Guidelines
A positive anti-centromere antibody (ACA) test at a titer of 1:1280 is highly suggestive of limited cutaneous systemic sclerosis, also known as CREST syndrome, and indicates a significant risk of developing pulmonary arterial hypertension (PAH) over time. This diagnosis is supported by the high specificity (97-99%) of ACAs for limited cutaneous systemic sclerosis, as noted in the context of connective tissue diseases and PAH 1. The presence of ACA is particularly relevant in the context of scleroderma, where it is associated with a subset of patients who are at higher risk of developing isolated PAH, especially those with long-standing limited scleroderma, disease onset after menopause, and certain other autoantibodies 1.
Clinical Implications
The significance of a positive ACA result at a titer of 1:1280 includes:
- A high likelihood of limited cutaneous systemic sclerosis (CREST syndrome), characterized by calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasias.
- An increased risk of developing PAH, which is a major complication in scleroderma patients and can lead to significant morbidity and mortality.
- The need for a comprehensive clinical evaluation, including:
- Pulmonary function tests to assess for interstitial lung disease and to measure the diffusing capacity of the lung for carbon monoxide (Dlco), which is often decreased in patients with PAH.
- Echocardiogram to evaluate right ventricular function and estimate pulmonary artery pressures.
- Regular monitoring for complications such as PAH, which may require serial echocardiograms and other tests.
Management
Management of patients with positive ACA and limited cutaneous systemic sclerosis typically involves organ-specific treatments, such as:
- Calcium channel blockers for Raynaud's phenomenon.
- Proton pump inhibitors for esophageal symptoms.
- Immunosuppressive therapy in cases of progressive disease. The high titer of 1:1280 confirms the presence of the antibody with high certainty but does not necessarily correlate with disease severity 1. Therefore, clinical management should be tailored to the individual patient's symptoms and disease manifestations.
From the Research
Significance of Positive Anti-Centromere Antibody
The presence of a positive anti-centromere antibody (ACA) result at a titer of 1:1280 is significant in the diagnosis and prognosis of certain autoimmune diseases.
- The anti-centromere antibody is closely associated with limited systemic sclerosis, particularly the CREST syndrome variant, which is characterized by calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia 2, 3, 4.
- Patients with ACA are more likely to be female and have a higher frequency of telangiectasiae of the digits and calcinosis 2.
- The presence of ACA is also associated with a lower frequency of pulmonary interstitial fibrosis and restrictive disease on pulmonary function testing 2.
- ACA can be found in patients without CREST or scleroderma, and its presence may indicate the presence of another underlying rheumatic or connective tissue disease, such as systemic lupus erythematosus or seronegative polyarthritis 5.
- The prevalence of ACA in certain populations, such as Thai patients, is low, and its presence does not always suggest a diagnosis of CREST syndrome, even at high titers 6.
Clinical Correlations
- The anti-centromere antibody is a useful prognostic indicator in patients with early scleroderma, as it may help predict the pattern of scleroderma that will evolve 3.
- Screening for ACA should be conducted in all patients with Raynaud's phenomenon, primary biliary cirrhosis, and scleroderma 3.
- The presence of ACA at a high titer, such as 1:1280, may indicate a more severe disease course or a higher risk of developing certain complications, such as calcinosis or telangiectasiae 2, 4.