A block in the road to fertility: autoantibodies to heat-shock protein 90-β in human ovarian autoimmunity

Pires, Eusebio S.; Khole, Vrinda

doi:10.1016/j.fertnstert.2008.08.068

Cited by 54 publications

(66 citation statements)

References 41 publications

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“…2, multiple molecular antigenic targets span a wide range of molecular weights from 25 kDa to 200 kDa. The most immunodominant antigen among all the targets was a 90 kDa protein identified to be human HSP90β as discussed in the earlier section of this review [16]. Other identified targets are in the process of being characterized.…”

Section: Discussionmentioning

confidence: 88%

“…Using a novel blocking recipe, Pires' group [8,11] demonstrated the presence of AOA in infertile women and the antibodies present in their circulation identified an immunodominant antigen-heat shock protein 90-beta (HSP90β). This protein predominantly stained the oocyte cytoplasm followed by immunoreacting to cells of the theca and to the interstitium of the corpus luteum [16]. HSP90β was demonstrated to be a major autoantigen and it was proposed that anti-HSP90 antibodies could be used as one of the diagnostic markers for ovarian failure and thereby infertility.…”

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confidence: 99%

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Multiplicity of molecular and cellular targets in human ovarian autoimmunity: an update

Pires

2010

J Assist Reprod Genet

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Section: Discussionmentioning

confidence: 88%

mentioning

confidence: 99%

Multiplicity of molecular and cellular targets in human ovarian autoimmunity: an update

Pires

2010

J Assist Reprod Genet

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“…Protein extracts were prepared and processed for electrophoresis as well as for transfer as discussed earlier [14]. Briefly, the transferred ovarian proteins were visualized using Ponceau S (Sigma, USA).…”

Section: Sds-page Western Blot Analysismentioning

confidence: 99%

“…This problem of non-specificity has been overcome in a specific, simple and non-invasive diagnostic test developed by us [13]. Using this test we could show new and true molecular and histochemical targets in the ovary in case of ovarian autoimmunity [5,14]. The next step would be to suppress the activity of these autoantibodies before commencing the ovarian stimulation protocol with a standardized dose of corticosteroids.…”

Section: Introductionmentioning

confidence: 99%

Can anti-ovarian antibody testing be useful in an IVF-ET clinic?

Pires

Parikh

Mande

et al. 2010

J Assist Reprod Genet

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Objective To establish importance of anti-ovarian antibodies (AOA) testing in infertile women. Design A clinical reproductive outcome comparative study between two groups of women undergoing IVF-ET. Group 1 consists of women tested positive for AOA, put on corticosteroid therapy, reverted to AOA negative and then taken up for IVF-ET. Group 2 were seronegative for AOA. Setting Major urban infertility reference centre and National research institute. Results AOA positive serum samples were sent periodically to re-investigate presence of AOA after corticosteroid therapy and women turned AOA negative were taken up for IVF-ET. Of the 70/138 women in group 1 who were treated with corticosteroids and turned seronegative for AOA, 22/70 were poor responders and needed donor oocyte-recipient cycles. Results demonstrated that fertilization and clinical pregnancy rates between both groups are comparable. Nevertheless, it is also observed that there is poor response to stimulation protocol, smaller number of oocytes retrieved and more spontaneous abortions in group 1 women. Hence not all outcomes following the treatment are comparable between the two groups. Usefulness of the test was established in two case studies. Conclusions AOA testing could be included in the battery of tests investigating and treating infertility.

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“…We demonstrated the presence of multiple antigenic targets in the range of 30-220 kDa, of which 45,80,90,97, and 120 kDa proteins were found to be predominantly targeted by the sera of infertile women. Four of these immunodominant ovarian autoantigens were identified and characterized extensively in our previous studies using sera of women with POI and women recruited under IVF-ET program (Pires & Khole 2009, Mande et al 2011). The three proteins, i.e.…”

Section: Introductionmentioning

confidence: 99%

Immunization with ovarian autoantigens leads to reduced fertility in mice following follicular dysfunction

Mande¹,

Thomas²,

Khan³

et al. 2012

Reproduction

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Immunoproteomics using sera of women with ovarian autoimmune diseases such as primary ovarian insufficiency and IVF embryo transfer recruits led to identification of three proteins namely alpha actinin 4 (a-ACTN4), heat-shock 70 protein 5 (HSPA5), and actin beta (ACTB). This study deals with the establishment of a peptide ELISA for screening sera of antiovarian antibody (AOA)-positive patients and further delves into understanding the role of these three proteins in ovarian autoimmunity in a mouse model. Using in silico approach, antigenic peptides of these proteins were identified and used for peptide ELISA. ELISA results indicated that AOA-positive sera showed reactivity with only specific peptides. The functional significance of the dominant peptides was studied by active immunization of female mice with these peptides. All immunized mice generated high antibody titers and profound effect on ovaries with few primordial (2.4G0.1, 2.4G0.2, and 2G0.1), primary (2.4G0.5, 1.7G0.3, and 2.4G0.3), preantral (2.3G0.5, 3.4G0.3, and 2.9G0.3), antral (0.9G0.2, 1.6G0.8, and 2.3G0.6) follicles, and corpora lutea (2.8G0.8, 2.9G1.7, and 4.6G2.3), and increased number of atretic follicles (5.5G0.4, 4.9G1.8, and 7.5G1.0) in ACTN4-, HSPA5-, and ACTB-immunized mice compared with control animals (3.0G0.2, 3.5G0.6, 3G0.1, 3.6G0.2, 4.7G0.3, and 1.5G0.3) respectively. These mice when mated with fertile male mice showed an overall 25-43% reduction in fertility compared with controls. The data clearly suggest that the dominant antigenic epitopes of the three proteins play critical role in fertility and could possibly be the key autoimmune targets. These epitopes could be used to develop a more specific and sensitive diagnostic test for women with ovarian autoimmune diseases and to design therapy for disease management for reinstatement of ovarian function.

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A block in the road to fertility: autoantibodies to heat-shock protein 90-β in human ovarian autoimmunity

Cited by 54 publications

References 41 publications

Multiplicity of molecular and cellular targets in human ovarian autoimmunity: an update

Multiplicity of molecular and cellular targets in human ovarian autoimmunity: an update

Can anti-ovarian antibody testing be useful in an IVF-ET clinic?

Immunization with ovarian autoantigens leads to reduced fertility in mice following follicular dysfunction

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