Steroid-cell autoantibodies are preferentially expressed in women with premature ovarian failure who have adrenal autoimmunity

Falorni, Alberto; Laureti, Stefano; Candeloro, Paola; Perrino, Silvia; Coronella, Concetta; Bizzarro, Antonio; Bellastella, Antonio; Santeusanio, Fausto; Bellis, Annamaria De

doi:10.1016/s0015-0282(02)03205-3

Cited by 106 publications

(91 citation statements)

References 40 publications

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“…Abs to the (as yet unidentified) 51 kDa antigen present in granulosa cells and in placenta have been described in a few patients with POF associated with APS type 1 and isolated AD (33) but their significance is not clear at present. The Abs to 3b-hydroxysteroid dehydrogenase in patients with POF have been reported (34); however, they are rare in POF patients (32) and in those with APS type 1 (35).…”

Section: Discussionmentioning

confidence: 99%

Autoantibodies to steroidogenic enzymes in patients with premature ovarian failure with and without Addison's disease

Prà

Chen²,

Furmaniak³

et al. 2003

European Journal of Endocrinology

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Design: Adrenal cortex autoantibodies (ACA), steroid-producing cell autoantibodies (StCA) and autoantibodies (Abs) to steroidogenic enzymes in three groups of patients with premature ovarian failure (POF), 15 with autoimmune Addison's disease (AD), 26 with non-adrenal autoimmune diseases and 31 with isolated POF, have been assessed. Methods: ACA and StCA were measured using an immunofluorescence technique. Abs to 21-hydroxylase (21-OH), to 17a-hydroxylase (17a-OH) and to cytochrome P450 side-chain cleavage (P450scc) were measured using an immunoprecipitation assay. Results: Seventy-three percent of patients with POF and AD were positive for StCA, 93% for 17a-OH and/or P450scc Abs, 93% for ACA and 100% for 21-OH Abs. Among patients with POF and nonadrenal autoimmune diseases, 8% were positive for StCA, 12% for 17a-OH and/or P450scc Abs, and 8% and 12% for ACA and 21-OH Abs respectively. StCA, 17a-OH and/or P450scc Abs were all found in 10% of patients with isolated POF, and 13% had ACA and 21-OH Abs. All StCA-, 17a-OH-and/or P450scc Abs-positive patients were also positive for ACA and 21-OH Abs. Two patients with isolated POF who were ACA and 21-OH Ab positive developed AD 3 and 5 years after the onset of POF. Conclusion: This study has shown that, when POF is associated with AD, StCA, 17a-OH and/or P450scc Abs are present in the majority of patients, while in the other two groups these Abs are detectable in a much lower proportion of patients. Measurement of ACA/21-OH Abs in some patients with POF may be important in identifying patients at risk of developing overt AD.

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Section: Discussionmentioning

confidence: 99%

Autoantibodies to steroidogenic enzymes in patients with premature ovarian failure with and without Addison's disease

Prà

Chen²,

Furmaniak³

et al. 2003

European Journal of Endocrinology

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“…Although women with POI have a poor ovarian follicle pool compared to healthy fertile women, women with POI and steroidogenic cell autoimmunity (SCA-POI), which involves circulating autoantibodies directed against steroidogenic enzymes such as 21-α-hydroxylase, 17-β-hydroxylase, and side-chain cleavage enzyme (P450sccAb) (72)(73)(74)(75)(76), have a better ovarian reserve than women with iPOI and postmenopausal women. Steroid sulphatase is controlled by an x-linked gene.…”

Section: Conversion To Other Steroidsmentioning

confidence: 99%

Dehydroepiandrosterone improves the ovarian reserve of women with diminished ovarian reserve and is a potential regulator of the immune response in the ovaries

Zhang

Gui

et al. 2015

BST

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“…In addition to autoantibodies to CYP21A2, autoantibodies to two other steroidogenic enzymes, P450 side chain cleavage (CYP11A1) and 17a-hydroxylase (CYP17), which convert cholesterol to pregnenolone, and progesterone to 17-hydroxyprogesterone, respectively, are present. 21,[25][26][27] Since these latter enzymes, unlike CYP21A2, are expressed in the ovary, the presence of these antibodies may signify the actual autoimmune targets of the ovary. Antibodies targeting P450ssc and CYP17 are termed 'steroid cell' (SC) antibodies, since in addition to binding the adrenal cortex, they bind placental syncytiotrophoblast cells, Leydig cells of the testes, and theca and luteal cells of the ovary.…”

Section: Autoimmune Oophoritis As a Cause For Primary Ovarian Insuffimentioning

confidence: 99%

“…Some reports also include 3b-hydroxysteroid dehydrogenase as a target of SC antibodies; however, others do not support this premise. 26,28,29 Although diagnostic markers of POI for use in the clinic have not been developed to date, adrenal cortex autoantibodies are predictive of autoimmune oophoritis. 21 Conversely, a patient presenting with POI who is found to possess SC autoantibodies should be closely monitored for emergent adrenal insufficiency because of its overlap with, and the life-threatening nature of, Addison's disease.…”

Section: Autoimmune Oophoritis As a Cause For Primary Ovarian Insuffimentioning

confidence: 99%

Ovarian autoimmune disease: clinical concepts and animal models

et al. 2014

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The ovary is not an immunologically privileged organ, but a breakdown in tolerogenic mechanisms for ovary-specific antigens has disastrous consequences on fertility in women, and this is replicated in murine models of autoimmune disease. Isolated ovarian autoimmune disease is rare in women, likely due to the severity of the disease and the inability to transmit genetic information conferring the ovarian disease across generations. Nonetheless, autoimmune oophoritis is often observed in association with other autoimmune diseases, particularly autoimmune adrenal disease, and takes a toll on both society and individual health. Studies in mice have revealed at least two mechanisms that protect the ovary from autoimmune attack. These mechanisms include control of autoreactive T cells by thymus-derived regulatory T cells, as well as a role for the autoimmune regulator (AIRE), a transcriptional regulator that induces expression of tissue-restricted antigens in medullary thymic epithelial cells during development of T cells. Although the latter mechanism is incompletely defined, it is well established that failure of either results in autoimmune-mediated targeting and depletion of ovarian follicles. In this review, we will address the clinical features and consequences of autoimmune-mediated ovarian infertility in women, as well as the possible mechanisms of disease as revealed by animal models.

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Steroid-cell autoantibodies are preferentially expressed in women with premature ovarian failure who have adrenal autoimmunity

Cited by 106 publications

References 40 publications

Autoantibodies to steroidogenic enzymes in patients with premature ovarian failure with and without Addison's disease

Autoantibodies to steroidogenic enzymes in patients with premature ovarian failure with and without Addison's disease

Dehydroepiandrosterone improves the ovarian reserve of women with diminished ovarian reserve and is a potential regulator of the immune response in the ovaries

Ovarian autoimmune disease: clinical concepts and animal models

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