Test/Range/Collection

Centromere antibodies, serum (ACA)

Negative

SST

$$

Separate serum from cells ASAP or within 2 hrs of collection, refrigerate or freeze.

Physiologic Basis

Centromere antibodies (ACA) are antibodies to nuclear proteins, specifically CENP-A, -B, and -C. The CENP-B is the primary autoantigen and is recognized by all sera that contain ACA.

Presence of ACA predicts a favorable prognosis for systemic sclerosis.

Both immunofluorescent antibody testing (IFA)- and enzyme-linked immunosorbent assay (ELISA)-based assays are available for ACA detection.

Interpretation

Positive in: CREST syndrome (calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia) (80–90%), diffuse scleroderma (5–10%), Raynaud disease (20–30%).

Comments

ACA correlate with limited skin involvement and high risk of vascular complications, eg, pulmonary hypertension. In patients with connective tissue disease, the predictive value of a positive ACA test is >95% for scleroderma or related disease (CREST syndrome, Raynaud disease). Nevertheless, diagnosis of CREST syndrome is made clinically.

The presence of detectable ACA may antedate the development of clinical CREST syndrome by several years.

In addition to ACA, tests for autoantibodies targeting topoisomerase-I and RNA polymerase also help diagnose and subclassify systemic sclerosis.

ACA is also present in a small percentage of patients with primary biliary cirrhosis, rheumatoid arthritis and systemic lupus erythematosus.

(See also Autoantibodies, Table 8–7 .)

Saketkoo LA et al. The primary care physician in the early diagnosis of systemic sclerosis: the cornerstone of recognition and hope. Am J Med Sci 2014;347:54.  [PMID: 24366221]

Tyndall A et al. The differential diagnosis of systemic sclerosis. Curr Opin Rheumatol 2013;25:692.  [PMID: 24061074]

Villalta D et al. Diagnostic accuracy and predictive value of extended autoantibody profile in systemic sclerosis. Autoimmun Rev 2012;12:114.  [PMID: 22776784]