ACAs that are relevant for scleroderma diagnosis are directed against the centromere-associated proteins (CENP) CENP-A (17 kDa), CENP-B (80 kDa), and CENP-C (140 kDa). CENP-B is the antigen most commonly targeted by ACAs. Autoantibodies directed against other centromeric proteins (e.g., proteins only transiently associated with the centromere) are not included in the "diagnostic-category" ACAs. The method of choice for detecting ACAs is indirect immunofluorescence (IIF) using monolayers of tumor cells (usually HEp-2). The number of spots corresponds to the number of chromosomes in interphase nuclei and in the equatorial plane of mitotic cells. If the typical ACA pattern is masked by other autoantibodies, an enzyme immunoassay using recombinant CENP-B protein should be used. ACAs are diagnostic markers for systemic sclerosis with a specificity of >95% (SSc versus other CTD) to nearly 100% (SSc versus normal controls) and a sensitivity of 20-30% in general (reviewed in ). The frequency varies in different ethnic and clinical groups. ACAs are most often seen in CREST syndrome and similar variants, with a relatively mild clinical course and lower mortality compared to SSc patients with anti-scl-70 or antinucleolar antibodies. The prevalence of interstitial pulmonary fibrosis and renal involvement in ACA-positive scleroderma patients is very low. However, ACA-positive patients do have an increased risk of pulmonary hypertension and ischemic digital loss. The occurrence of ACAs in high-risk patients or patients with Raynaud's phenomenon is an important indicator of the potential for SSc development [22-24, 26]. ACAs can be detected years before the occurrence of specific symptoms of scleroderma. ACAs are also detectable in patients with primary biliary cirrhosis (PBC). Roughly half of these patients have concomitant scleroderma or signs of the development of scleroderma (e.g., Raynaud's phenome non). ACAs are infrequently detectable in circumscribed forms of scleroderma as well as in SLE, polymyositis/dermatomyositis, primary pulmonary hypertension, and chronic active hepatitis. Positive ACA test results can also indicate the potential for the development of scleroderma in these patients.
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