Abstract
Background. We undertook this study to examine the X chromosome complement in subjects with systemic sclerosis (SSc) as well as idiopathic inflammatory myopathies.
Methods. The subjects met classification criteria for the respective diseases. All underwent single nucleotide polymorphism typing. We examined X and Y SNP heterogeneity to determine the number of X chromosomes. For statistical comparisons, we used chi square analyses with calculation of 95% confidence intervals.
Results. Three of 70 men with SSc had 47,XXY (p=0.0001 compared to control men). Among the 435 SSc women, none had 47,XXX. Among 709 men with polymyositis or dermatomyositis (PM/DM), 7 had 47,XXY (p=0.0016), while among the 1783 women, 2 had 47,XXX. Six of 147 men with inclusion body myositis (IBM) had 47,XXY and 1 of the 114 women had 47,XXX. For each of these myositis disease groups, the excess 47,XXY and/or 47,XXX was significantly higher compared to controls as well as the known birth rate of Klinefelter’s syndrome or 47,XXX.
Conclusion. Klinefelter’s syndrome (47,XXY) is associated with SSc and idiopathic inflammatory myopathies, similar to other autoimmune diseases with type 1 interferon pathogenesis; namely, systemic lupus erythematosus, and Sjögren’s syndrome.
Key Messages
- Autoimmune rheumatic diseases generally impact women more than men
- A strong component to such bias in systemic lupus erythematosus and Sjögren’s syndrome is
mediated by the sex chromosome complement
- We find the number of X chromosomes also is important in the sex bias of systemic sclerosis and
idiopathic inflammatory myopathies
- These diseases all share pathophysiology involving type 1 interferon pathways
Methods. The subjects met classification criteria for the respective diseases. All underwent single nucleotide polymorphism typing. We examined X and Y SNP heterogeneity to determine the number of X chromosomes. For statistical comparisons, we used chi square analyses with calculation of 95% confidence intervals.
Results. Three of 70 men with SSc had 47,XXY (p=0.0001 compared to control men). Among the 435 SSc women, none had 47,XXX. Among 709 men with polymyositis or dermatomyositis (PM/DM), 7 had 47,XXY (p=0.0016), while among the 1783 women, 2 had 47,XXX. Six of 147 men with inclusion body myositis (IBM) had 47,XXY and 1 of the 114 women had 47,XXX. For each of these myositis disease groups, the excess 47,XXY and/or 47,XXX was significantly higher compared to controls as well as the known birth rate of Klinefelter’s syndrome or 47,XXX.
Conclusion. Klinefelter’s syndrome (47,XXY) is associated with SSc and idiopathic inflammatory myopathies, similar to other autoimmune diseases with type 1 interferon pathogenesis; namely, systemic lupus erythematosus, and Sjögren’s syndrome.
Key Messages
- Autoimmune rheumatic diseases generally impact women more than men
- A strong component to such bias in systemic lupus erythematosus and Sjögren’s syndrome is
mediated by the sex chromosome complement
- We find the number of X chromosomes also is important in the sex bias of systemic sclerosis and
idiopathic inflammatory myopathies
- These diseases all share pathophysiology involving type 1 interferon pathways
| Original language | English |
|---|---|
| Journal | ACR Open Rheumatology |
| Publication status | Accepted/In press - 10 Jan 2022 |