Abstract
The majority of human autoimmune diseases are characterized by female predominance. Although sex hormone influences have been suggested to explain this phenomenon, the mechanism remains unclear. In contrast to the role of hormones, it has been suggested, based on pilot data in primary biliary cirrhosis, that there is an elevation of monosomy X in autoimmune disease. Using peripheral white blood cells from women with systemic sclerosis (SSc), autoimmune thyroid disease (AITD), or healthy age-matched control women, we studied the presence of monosomy X rates using fluorescence in situ hybridization. We also performed dual-color fluorescence in situ hybridization analysis with a chromosome Y α-satellite probe to determine the presence of the Y chromosome in the monosomic cells. In subsets of patients and controls, we determined X monosomy rates in white blood cell subpopulations. The rates of monosomy X increased with age in all three populations. However, the rate of monosomy X was significantly higher in patients with SSc and AITD when compared with healthy women (6.2 ± 0.3% and 4.3 ± 0.3%, respectively, vs 2.9 ± 0.2% in healthy women, p < 0.0001 in both comparisons). Importantly, X monosomy rate was more frequent in peripheral T and B lymphocytes than in the other blood cell populations, and there was no evidence for the presence of male fetal microchimerism. These data highlight the thesis that chromosome instability is common to women with SSc and AITD and that haploinsufficiency for X-linked genes may be a critical factor for the female predominance of autoimmune diseases.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 575-578 |
| Number of pages | 4 |
| Journal | Journal of Immunology |
| Volume | 175 |
| Issue number | 1 |
| State | Published - Jul 1 2005 |
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ASJC Scopus subject areas
- Immunology
Cite this
X chromosome monosomy : A common mechanism for autoimmune diseases. / Invernizzi, Pietro; Miozzo, Monica; Selmi, Carlo; Persani, Luca; Battezzati, Pier Maria; Zuin, Massimo; Lucchi, Simona; Meroni, Pier Luigi; Marasini, Bianca; Zeni, Silvana; Watnik, Mitchell; Grati, Francesca R.; Simoni, Giuseppe; Gershwin, M. Eric; Podda, Mauro.
In: Journal of Immunology, Vol. 175, No. 1, 01.07.2005, p. 575-578.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - X chromosome monosomy
T2 - A common mechanism for autoimmune diseases
AU - Invernizzi, Pietro
AU - Miozzo, Monica
AU - Selmi, Carlo
AU - Persani, Luca
AU - Battezzati, Pier Maria
AU - Zuin, Massimo
AU - Lucchi, Simona
AU - Meroni, Pier Luigi
AU - Marasini, Bianca
AU - Zeni, Silvana
AU - Watnik, Mitchell
AU - Grati, Francesca R.
AU - Simoni, Giuseppe
AU - Gershwin, M. Eric
AU - Podda, Mauro
PY - 2005/7/1
Y1 - 2005/7/1
N2 - The majority of human autoimmune diseases are characterized by female predominance. Although sex hormone influences have been suggested to explain this phenomenon, the mechanism remains unclear. In contrast to the role of hormones, it has been suggested, based on pilot data in primary biliary cirrhosis, that there is an elevation of monosomy X in autoimmune disease. Using peripheral white blood cells from women with systemic sclerosis (SSc), autoimmune thyroid disease (AITD), or healthy age-matched control women, we studied the presence of monosomy X rates using fluorescence in situ hybridization. We also performed dual-color fluorescence in situ hybridization analysis with a chromosome Y α-satellite probe to determine the presence of the Y chromosome in the monosomic cells. In subsets of patients and controls, we determined X monosomy rates in white blood cell subpopulations. The rates of monosomy X increased with age in all three populations. However, the rate of monosomy X was significantly higher in patients with SSc and AITD when compared with healthy women (6.2 ± 0.3% and 4.3 ± 0.3%, respectively, vs 2.9 ± 0.2% in healthy women, p < 0.0001 in both comparisons). Importantly, X monosomy rate was more frequent in peripheral T and B lymphocytes than in the other blood cell populations, and there was no evidence for the presence of male fetal microchimerism. These data highlight the thesis that chromosome instability is common to women with SSc and AITD and that haploinsufficiency for X-linked genes may be a critical factor for the female predominance of autoimmune diseases.
AB - The majority of human autoimmune diseases are characterized by female predominance. Although sex hormone influences have been suggested to explain this phenomenon, the mechanism remains unclear. In contrast to the role of hormones, it has been suggested, based on pilot data in primary biliary cirrhosis, that there is an elevation of monosomy X in autoimmune disease. Using peripheral white blood cells from women with systemic sclerosis (SSc), autoimmune thyroid disease (AITD), or healthy age-matched control women, we studied the presence of monosomy X rates using fluorescence in situ hybridization. We also performed dual-color fluorescence in situ hybridization analysis with a chromosome Y α-satellite probe to determine the presence of the Y chromosome in the monosomic cells. In subsets of patients and controls, we determined X monosomy rates in white blood cell subpopulations. The rates of monosomy X increased with age in all three populations. However, the rate of monosomy X was significantly higher in patients with SSc and AITD when compared with healthy women (6.2 ± 0.3% and 4.3 ± 0.3%, respectively, vs 2.9 ± 0.2% in healthy women, p < 0.0001 in both comparisons). Importantly, X monosomy rate was more frequent in peripheral T and B lymphocytes than in the other blood cell populations, and there was no evidence for the presence of male fetal microchimerism. These data highlight the thesis that chromosome instability is common to women with SSc and AITD and that haploinsufficiency for X-linked genes may be a critical factor for the female predominance of autoimmune diseases.
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UR - http://www.scopus.com/inward/citedby.url?scp=21244456843&partnerID=8YFLogxK
M3 - Article
C2 - 15972694
AN - SCOPUS:21244456843
VL - 175
SP - 575
EP - 578
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 1
ER -