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).


CONCLUSIONS
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.
Porciello
Giovanni
G
Istituto di Reumatologia, University of Siena, Italy. g.porciello@katamail.com
Scarpato
Roberto
R
Ferri
Clodoveo
C
Storino
Franca
F
Cagetti
Francesca
F
Morozzi
Gabriella
G
Bellisai
Francesca
F
Migliore
Lucia
L
Marcolongo
Roberto
R
Galeazzi
Mauro
M
D000328:Adult; D001323:Autoantibodies / Q000097:blood; D002869:Chromosome Aberrations; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D048629:Micronuclei, Chromosome-Defective; D008875:Middle Aged; D011928:Raynaud Disease / Q000235:genetics* / Q000276:immunology; D012595:Scleroderma, Systemic / Q000235:genetics* / Q000276:immunology
D001323:Autoantibodies