47XXY and 47XXX in Scleroderma and Myositis

Abstract

Objective We undertook this study to examine the X chromosome complement in participants with systemic sclerosis (SSc) as well as idiopathic inflammatory myopathies. Methods The participants met classification criteria for the diseases. All participants underwent single‐nucleotide polymorphism typing. We examined X and Y single‐nucleotide polymorphism heterogeneity to determine the number of X chromosomes. For statistical comparisons, we used χ2 analyses with calculation of 95% confidence intervals. Results Three of seventy men with SSc had 47,XXY (P = 0.0001 compared with control men). Among the 435 women with SSc, none had 47,XXX. Among 709 men with polymyositis or dermatomyositis (PM/DM), seven had 47,XXY (P = 0.0016), whereas among the 1783 women with PM/DM, two had 47,XXX. Of 147 men with inclusion body myositis (IBM), six had 47,XXY, and 1 of the 114 women with IBM had 47,XXX. For each of these myositis disease groups, the excess 47,XXY and/or 47,XXX was significantly higher compared with in controls as well as the known birth rate of Klinefelter syndrome or 47,XXX. Conclusion Klinefelter 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 syndrome.

Morbidity, mortality, and socioeconomics in Klinefelter syndrome and 47,XYY syndrome: a comparative review

“…Exceptions are autoimmune diseases like ankylosing spondylitis and Goodpasture's disease, which are not seen more frequently among KS males (7). A likely explanation KS males are known to have impaired bone metabolism, reduced bone mass density (BMD) (11), and a prevalence of osteoporosis of 5-10% and approximately 40% for osteopenia (12). Relative or manifest hypogonadism and a higher prevalence of metabolic syndrome are some factors that potentially decrease BMD.…”

Altered X-chromosome inactivation predisposes to autoimmunity

“…While these differences are partly attributable to sex hormones, X-linked factors represent other likely contributors (1)(2)(3)(4)(5)(6). Men with Klinefelter's syndrome, who bear an extra X chromosome (47,XXY) in a male hormonal context, have a risk equivalent to women to develop relatively rare immune disorders such as systemic lupus erythematosus (SLE) (7), Sjogren's syndrome (8), or Systemic Sclerosis (9). Moreover, the female bias in autoimmune diseases such as SLE is observed before puberty (10).…”

Recent advances in elucidating the genetic basis of systemic sclerosis

“…An interesting finding was also found through the characterization of patients with both IMDs and sex-chromosome trisomies. A study by Scofield et al [53] revealed an association of the Klinefelter syndrome (47, XXY) with SSc and idiopathic inflammatory myopathies.…”