Chromosome aberrations in Raynaud's phenomenon.

We evaluated the occurrence of spontaneous chromosome damage in cultured peripheral lymphocytes of subjects with idiopathic and pre-scleroderma Raynaud's phenomenon, by means of molecular cytogenetic analysis. Using the micronucleus assay as a marker of chromosome alteration, we studied 30 patients with pre-scleroderma Raynaud's phenomenon, 30 patients with idiopathic Raynaud's phenomenon and 30 healthy subjects. All subjects were classified as ANA-, ACA+ or Scl 70+. To identify the mechanism of micronucleus formation, fluorescence in situ hybridisation analysis was also performed. Pre-scleroderma Raynaud's phenomenon subjects showed significantly higher micronucleus frequencies than idiopathic Raynaud's phenomenon subjects and controls (37.0 +/- 11.5 vs. 11.1 +/- 3.2 and 10.7 +/- 2.7 respectively p < 0.0001). Interestingly, subjects with idiopathic Raynaud's phenomenon displayed micronucleus frequency comparable to that of healthy controls. Furthermore, ACA+ subjects showed the highest micronucleus frequencies (41.0 +/- 7.6) as compared to subjects with Scl 70+ antibody (25.0 +/- 3.5). Our results show that circulating lymphocytes of only pre-scleroderma Raynaud's phenomenon subjects undergo chromosomal damage, as detected by the micronucleus assay, at a higher rate than expected. No prevalence of aneuploidogenic or clastogenic events in micronucleus formation is revealed by fluorescence in situ hybridisation analysis.

Spontaneous chromosome damage (micronuclei) in systemic sclerosis and Raynaud's phenomenon.

OBJECTIVE: To evaluate the prevalence of spontaneous chromosome damage in cultured peripheral lymphocytes of patients with systemic sclerosis (SSc), idiopathic Raynaud's phenomenon (RP), and suspected secondary RP, by means of molecular cytogenetic analysis. METHODS: We studied 43 patients with SSc, 13 with idiopathic RP, and 16 with suspected secondary RP and 25 healthy controls. As a marker of chromosome alteration we used the micronucleus (MN) assay. All subjects were also classified for antinuclear antibodies, anticentromere antibodies (ACA), or Scl70. To identify the mechanism of MN formation, we also performed MN fluorescence in situ hybridization (FISH) analysis using a pancentromeric DNA probe. RESULTS: Patients with SSc and subjects with RP showed significantly higher MN frequencies than controls (25.9 +/- 1.7 and 19.1 +/- 2.15, respectively, vs 9.4 +/- 2.2; p < 0.001). Subjects with suspected secondary RP displayed MN frequency (23.5 +/- 2.7) comparable to that of SSc patients, while spontaneous MN level in idiopathic RP subjects (13.6 +/- 3.0) did not differ significantly from controls (9.4 +/- 2.2). ACA positive subjects showed the highest MN frequencies (32.8 +/- 1.7) compared to subjects with a different antibody pattern (18.3 +/- 1.6). CONCLUSION: Our results show the presence of higher levels of micronuclei in circulating lymphocytes of patients with SSc and subjects with suspected secondary RP. They also suggest a possible role of ACA in determining cytogenetic anomalies. FISH analysis indicated that both aneuploidogenic and clastogenic events contributed to the formation of MN observed in SSc patients and subjects with suspected secondary RP.