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B cells from anti-thyroid antibody positive, infertile women show hyper-reactivity to BCR stimulation.

ABSTRACT: Anti-thyroid antibody (ATA) positivity affects 1 out of 9 women in childbearing age and presents a significant risk for infertility. Emerging evidence indicates that alterations in the B cell receptor induced calcium (Ca²⁺) signaling could be key in the development of autoimmunity. We aimed to investigate the Ca²⁺ flux response of B lymphocyte subsets to BCR stimulation in Hashimoto's thyroiditis and related infertility. We collected peripheral blood samples from ATA+, infertile, euthyroid patients (HIE), hypothyroid, ATA+ patients before (H1) and after levothyroxine treatment (H2), and age-matched healthy controls (HC). All B cell subsets of ATA+, infertile, euthyroid patients showed elevated basal Ca²⁺ level and hyper-responsivity to BCR ligation compared to the other groups, which could reflect altered systemic immune function. The Ca²⁺ flux of hypothyroid patients was similar to healthy controls. The levothyroxine-treated patients had decreased prevalence of CD25⁺ B cells and lower basal Ca²⁺ level compared to pre-treatment. Our results support the role of altered Ca²⁺ flux of B cells in the early phase of thyroid autoimmunity and infertility.

SUBMITTER: Sereny-Litvai T

PROVIDER: S-EPMC9641243 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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B cells from anti-thyroid antibody positive, infertile women show hyper-reactivity to BCR stimulation.

Serény-Litvai Timea T Bajnok Anna A Temesfoi Viktoria V Nörenberg Jasper J Pham-Dobor Greta G Kaposi Ambrus A Varnagy Akos A Kovacs Kalman K Pentek Sandor S Koszegi Tamas T Mezosi Emese E Berki Timea T

Frontiers in immunology 20221025

Anti-thyroid antibody (ATA) positivity affects 1 out of 9 women in childbearing age and presents a significant risk for infertility. Emerging evidence indicates that alterations in the B cell receptor induced calcium (Ca<sup>2+</sup>) signaling could be key in the development of autoimmunity. We aimed to investigate the Ca<sup>2+</sup> flux response of B lymphocyte subsets to BCR stimulation in Hashimoto's thyroiditis and related infertility. We collected peripheral blood samples from ATA+, infe ...[more]

PMID: 36389812

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Project description:Study questionAre infertile women who screen positive for depression less likely to initiate infertility treatments?Summary answerInfertile women who screen positive for depression are less likely to initiate treatment for infertility.What is already knownInfertility imposes a psychological burden on many couples. Depression and anxiety have been demonstrated in ~40% of infertile women, which is twice that of fertile women. Further, the psychological burden associated with infertility treatment has been cited as a major factor for discontinuation of infertility care.Study design, size, durationProspective, observational study in a clinical-based cohort of 416 women who completed a questionnaire after the new patient visit, from January 2013 until December 2014 inclusive.Participants/materials, setting, methodsAll new female infertility patients (n = 959) seen between January 2013 and December 2014 at University of North Carolina Fertility received an electronic questionnaire to screen for mental health disorders and to evaluate their perception of mental health disorders on infertility.Main results and the role of chanceOf 959 surveys sent, 416 women completed the questionnaire (43%). The prevalence screening positive for depression, using the NIH PROMIS screening tool, was 41%. Sixty-two percent of all women initiated infertility treatment, and of these, 81% did so within 4 months. In multivariate analysis, women who screened positive for depression had 0.55 times the odds of initiating treatment for infertility (95% CI: 0.31-0.95). Similarly, women who screened positive for depression had 0.58 times the odds of initiating infertility treatment within 4 months (95% CI: 0.35-0.97), which was the time of censoring from the most recent patient evaluated. Women who screened positive for depression were less likely to pursue treatment with oral medications or IVF (P = 0.01 and P = 0.03, respectively), as compared to women who did not screen positive for depression.Limitations, reasons for cautionQuestionnaire-based evaluations may result in a lower prevalence of psychological disorder as some participants feign emotional well-being. Although we did not identify differences in women who responded to our survey and those who did not, responder bias may still be present. In addition, infertility is a couple's disease. However, this study only included psychological evaluation of the female partner. We have no information about the women's previous treatment.Wider implications of the findingsScreening for depression is important in the infertility patient population, as further evaluation and psychological interventions may improve compliance with fertility treatments, quality of life, and potentially, the overall chance of pregnancy.Study funding/competing interestsNone.

Project description:ObjectiveTo investigate the association between thyroid dysfunction or thyroid autoimmunity (TAI) and diminished ovarian reserve (DOR).MethodsA total of 2,867 women undergoing their first in-vitro fertilization (IVF) cycle at Shenzhen Zhongshan Obstetrics & Gynecology Hospital between January 1, 2013 and June 30, 2021, were enrolled in this study. The participants had documented thyroid and ovarian reserve metrics. They were categorized into three groups based on their thyroid function: normal thyroid function (N = 2,540), subclinical/overt hypothyroidism (SCH/OH) (N = 290), and subclinical/overt hyperthyroidism (N = 37). Anti-Mullerian hormone (AMH) and antral follicle count (AFC) were assessed and collected. Women with AMH <1.2 ng/mL and AFC < 5 were diagnosed with DOR. Basic characteristics and ovarian reserve-related parameters were compared among the three groups. The association between thyroid function and ovarian reserve function was further analyzed using logistical regression analyses. In addition, the euthyroid population was stratified using a thyroid-stimulating hormone (TSH) threshold of 2.5 µIU/mL, and the ovarian reserve-related parameters were compared among women with low-normal TSH (TSH < 2.5 µIU/mL), high-normal TSH (2.5 µIU/mL ≤ TSH ≤ 4.2 µIU/mL) and SCH/OH.ResultsWomen with SCH/OH had lower AMH levels (2.79 ng/mL vs. 3.41 ng/mL, P < 0.001) and a significantly higher prevalence of AMH level < 1.2ng/mL (17.2% vs. 12.1%, P = 0.015) compared to those with normal thyroid function. The prevalence of DOR was also higher among women with SCH/OH (10.0% vs. 6.5%, P = 0.036). There were no significant differences in ovarian reserve between women with normal thyroid function and those with subclinical/overt hyperthyroidism. Logistic regression analyses showed that the odds ratio (OR) of women with SCH/OH suffering from DOR was 1.666 (95% CI: 1.079-2.572) compared to those with normal thyroid function, after adjusting for TAI status and basic clinical characteristics. When the euthyroid group was stratified according to TSH levels, women with SCH/OH showed significantly lower AMH levels compared to women with low-normal TSH (2.79 ng/mL vs. 3.44 ng/mL, P < 0.001) and a significantly higher prevalence of DOR (10.0% vs. 6.0%, P = 0.010). Logistic regression analyses showed that the women with SCH/OH had an increased prevalence of DOR (OR: 1.819, 95% CI: 1.158-2.858) compared to those with low-normal TSH, after adjusting for TAI status and basic clinical characteristics. However, the OR for DOR among women with high-normal TSH was not significantly elevated compared to those with low-normal TSH (OR: 1.310, 95% CI: 0.936-1.832).ConclusionSCH/OH may be associated with DOR, irrespective of TAI status.

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B cells from anti-thyroid antibody positive, infertile women show hyper-reactivity to BCR stimulation.

Publications

B cells from anti-thyroid antibody positive, infertile women show hyper-reactivity to BCR stimulation.

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