Prognostic significance of anticentromere antibodies and anti–topoisomerase i antibodies in Raynaud's disease. A prospective study

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Abstract
Seventy-seven patients with Raynaud's disease were studied for a mean of 4 years (range 1–11 years) to determine the relationship between autoantibodies and long-term clinical outcome. Anticentromere antibodies (ACA) were assayed by indirect immunofluorescence and by immunoblotting of HeLa cell chromosome extracts. Antibodies to topoisomerase I (anti–topo I) were assayed by immunodiffusion and immunoblotting. Antibodies to the major centromeric protein, CENP-B, and anti–topo I were studied by enzyme-linked immunosorbent assay (ELISA). Eight patients developed telangiectasias, 4 developed skin tightening, and 4 developed a connective tissue disease other than scleroderma. The presence of ACA at the start of the study was associated with the development of telangiectasias (P < 0.003). An initial 100-kd band on immunoblot in conjunction with a positive anti–topo I ELISA result was associated with the development of tight skin (P < 0.0025), while a 100-kd band with a negative anti–topo I ELISA result was associated with the subsequent development of a connective tissue disease other than scleroderma (P < 0.0073). Patients who were initially ACA positive, had the 100-kd band on immunoblot, or had positive ELISA results for anti–topo I or for anti-CENP-B were 63-fold more likely to develop signs of connective tissue disease by the end of the study (P < 0.000009). The presence of any of these autoantibodies was more sensitive (100%), although less specific (75%), than were findings from nailfold capillaroscopy (sensitivity 67% and specificity 95%) in predicting subsequent clinical progression. We conclude that findings of assays for anti–topo I and ACA complement the findings from nailfold capillaroscopy in providing useful prognostic information in Raynaud's disease.