A CASE OF SLE ASSOCIATED WITH TURNER'S SYNDROME OF 45, XO/46, XXq&lt;sup&gt;+&lt;/sup&gt; MOSAICISM

Takegami, Toshihiko; Nakao, Kimihiko; Nagayama, Yuji; Fujita, Takahisa; Hoshino, Tatsuji; Tsunematsu, T; Imura, Hideto; Itani, Salam; Fukase, Masaaki

doi:10.2169/naika.69.861

Cited by 10 publications

(9 citation statements)

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“…However, this patient and family were identified by canvassing physicians caring for SLE patients for a patient with both SLE and Turner’s syndrome, not by our usual recruitment methods. There are only 2 previous case reports of Turner’s syndrome and SLE occurring together [14,15]. Thus, 45,XO is certainly not over-represented among women with SLE, although the present data do not allow determination of the relative risk of SLE in 45,XO women compared to 46,XX women, analogous to that made for Klinefelter’s syndrome.…”

Section: Sex Chromosome Abnormalities and Slecontrasting

confidence: 69%

Autoimmunity and Klinefelter's syndrome: When men have two X chromosomes

Sawalha

Harley

Scofield

2009

Journal of Autoimmunity

132

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Similar to other autoimmune diseases, systemic lupus erythematosus (SLE) predominately affects women. Recent reports demonstrate excess Klinefelter’s among men with SLE and a possible under-representation of Turner’s syndrome among women with SLE as well as a case report of a 46,XX boy with SLE. These data suggest that risk of SLE is related to a gene dose effect for the X chromosome. Such an effect could be mediated by abnormal inactivation of genes on the X chromosome as has been demonstrated for CD40L, or by genetic polymorphism as has been demonstrated for Xq28. On the other hand, a gene dose effect could also be mediated by a gene without an SLE-associated polymorphism in that a gene that avoids X inactivation will have a higher level of expression in persons with two X chromosomes.

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Section: Sex Chromosome Abnormalities and Slecontrasting

confidence: 69%

Autoimmunity and Klinefelter's syndrome: When men have two X chromosomes

Sawalha

Harley

Scofield

2009

Journal of Autoimmunity

132

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“…In this same study, we found that no woman with SLE had Turner's syndrome (4). Further, while there are numerous case reports of Klinefelter's men with SLE (4, reviewed in 22), we find only two previous reports of SLE in women with Turner's syndrome: one confirmed and characterized case (7) and one alleged case (8). We identified the present family by specifically canvassing our collaborators for patients with both Turner's syndrome and SLE.…”

Section: Discussioncontrasting

confidence: 56%

“…The previous characterized patient with Turner's syndrome/SLE overlap has 45,X/46,XXq+ mosaicism, or a mosaic short-arm deletion of one X chromosome (7) (Table 1). The present report of Turner's syndrome/SLE overlap documents a partial long arm deletion of the second X chromosome [46,X,del(X)(q13)] without mosaicism.…”

Section: Discussionmentioning

confidence: 99%

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46,X,del(X)(q13) Turner's syndrome women with systemic lupus erythematosus in a pedigree multiplex for SLE

et al. 2009

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Systemic lupus erythematosus (SLE) disproportionately affects females. Recent work demonstrates that men with Klinefelter's syndrome (47,XXY males) have a similar risk of developing SLE as do genotypic females. We present an unusual case of an African American family with two SLE affected individuals in which one of the SLE patients also has Turner's syndrome [46,X,del(X)(q13)]. While not definitive, this family raises interesting questions regarding the role of genes located on the X chromosome in the development of SLE. The paucity of case reports documenting the overlap of SLE with Turner's syndrome while there is and association of male SLE with Klinefelter's syndrome suggests a lower risk of SLE in Turner's females. These observations are consistent with a gene dose effect at X with two X chromosomes (46,XX or 47,XXY) conferring higher risk and one X chromosome (46,XY or 45,XO) conferring lower risk of SLE.

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“…Interestingly, patients with Turner syndrome have a higher risk of developing autoimmune diseases than do females in general (72). However, patients with Turner syndrome exhibit a greater risk of autoimmune diseases characterized by male predominance (72), and Turner syndrome rarely overlaps with the profoundly femalebiased disease SLE (73)(74)(75). Symptoms that appear in patients with Klinefelter syndrome also suggest a role for genes on the partially inactivated X chromosome in the immune system.…”

Section: Ifns and Feedback Loops Involving Sex Hormonesmentioning

confidence: 99%

Sexual dimorphism in autoimmunity

Rubtsova¹,

Marrack²,

Rubtsov³

2015

J. Clin. Invest.

175

127

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R e v i e w S e R i e S : A u t o i m m u n i t y 2 1 8 8jci.org Volume 125 Number 6 June 2015expression of IFN1 genes is controlled directly by sex hormones. On the other hand, sex hormones do affect expression of some of the PRRs (see below) and in this way might indirectly affect IFN1 levels. Thus, the abundance of IFN1s in lupus patients might be caused by female sex hormone-induced increases in PRR levels, which in turn increase production of IFN1s. One of the genes that controls expression of IFN1s is IFN regulatory factor 5 (IRF5). IRF5 has also been identified as a significant risk factor for lupus susceptibility (37,38). Expression of IRF5 in mice has been reported to be sex dependent (39). As demonstrated by Shen and colleagues (39), C57BL/6, NZB, Nba2, NZB/NZW F1, and NZM mouse strains express significantly higher levels of Irf5 mRNA in female than in male lymphocytes. Additionally, splenocytes from lupus-prone mice were shown to express higher levels of Irf5 mRNA compared with cells from the C57BL/6 strain, which is not prone to lupus. This group further demonstrated that Irf5 expression can be upregulated in vitro upon estrogen treatment, suggesting a potential mechanism for sex-biased expression of the gene and consequent overproduction of IFN1s (39).Absence of IFN-γ signaling protects NZB/NZW F1 mice against lupus-like disease (40). Expression of the IFNG gene, on the other hand, is regulated directly by estrogens (41)(42)(43)(44)(45). This finding suggests a positive feedback loop between the IFNs and estrogens, since activation of IFN1 or IFN-γ signaling upregulates the expression of ERα (46). Estrogen, in turn, promotes IFN-γ production by various lymphocytes. In addition, Panchanathan et al. demonstrated synergistic involvement of ERα and IFN signaling in activating the transcription of both IFN and estrogen-responsive target genes (46).Once produced, IFNs have many effects on the immune system that contribute to the sex bias of autoimmunity. For example, IFN1s increase class 1 MHC expression on cells, and IFN-γ induces class II MHC and changes the nature of the proteasome, thereby affecting the nature and quantity of self-peptides presented to T cells. Other examples are described below. Other immune-associated genes affected by sex hormonesMany genes with products that affect the immune system are controlled by sex hormones. As far as innate immunity is concerned, estrogens induce the expression of intracellular but not surface TLRs in both male and female PBMCs (23). Because intracellular TLRs have been shown to affect the development of autoimmunity (47-51), it is possible that the hormonal effect of the expression of intracellular TLRs contributes to female-biased autoimmunity.Unc-93 homolog B1 (UNC93B1) is an endoplasmic reticulum (ER) transmembrane protein that is essential for trafficking the TLRs that are expressed intracellularly (TLR3, TLR7, TLR8, TLR9, and probably other TLRs) from the ER to endosomes (52-54). UNC93B1 regulates the activity of these TLRs by mediating localization t...

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A CASE OF SLE ASSOCIATED WITH TURNER'S SYNDROME OF 45, XO/46, XXq<sup>+</sup> MOSAICISM

Cited by 10 publications

References 0 publications

Autoimmunity and Klinefelter's syndrome: When men have two X chromosomes

Autoimmunity and Klinefelter's syndrome: When men have two X chromosomes

46,X,del(X)(q13) Turner's syndrome women with systemic lupus erythematosus in a pedigree multiplex for SLE

Sexual dimorphism in autoimmunity

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