Abstract
Problem: Interleukin-17A (IL-17A) has a role in sustaining normal pregnancy. IL-17A is also associated with thyroid autoimmunity during pregnancy. This study sought to investigate whether IL-17A is a risk factor for thyroid dysfunction during pregnancy in women negative for thyroid autoantibodies.Methods of Study: The study comprised 216 pregnant women with negative thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TGAb) during the second trimester who provided blood samples for serum IL-17A, thyroid autoantibodies and thyroid function tests. To further evaluate the ratio of CD4+IL-17A+ Th17 cells, we collected peripheral blood from 26 women with thyroid-stimulating hormone (TSH) levels ≤ 2.5 mIU/L and 26 pregnancy-week matched women with TSH levels >2.5 mIU/L, along with samples from 20 women with TSH levels ≤ 4 mIU/L and 20 pregnancy-week matched women with TSH levels >4 mIU/L.Results: The serum IL-17A levels and ratios of CD4+IL-17A+ cells were significantly lower in women with TSH > 2.5 mIU/L than in those with TSH ≤ 2.5 mIU/L (both P < 0.01). Similar lower differences were noted in women with TSH > 4 mIU/L than in those with TSH ≤ 4 mIU/L (both P < 0.01). Moreover, serum TSH correlated negatively with IL-17A levels (β = −0.195, P = 0.004), but positively with the week of gestation (β = 0.284, P < 0.001). Logistic regression indicated that a lower serum IL-17A level was a risk factor for TSH > 2.5 mIU/L [OR = 0.453 (0.298–0.689), P = 0.000] and TSH > 4.0 mIU/L [OR = 0.588 (0.385–0.899), P = 0.013].Conclusion: A low serum IL-17A level during the second trimester is associated with an increased risk of TSH > 2.5 mIU/L and subclinical hypothyroidism.
Highlights
During a successful pregnancy, the maternal immune system must be immunologically tolerant to the semi-allograft fetus by suppressing the maternal alloreactive response against paternal antigens
A low serum IL-17A level during the second trimester is associated with an increased risk of thyroid-stimulating hormone (TSH) > 2.5 mIU/L and subclinical hypothyroidism
To identify changes in cytokines levels based on serum TSH, we examined the IL-17A, IL-4, and tumor necrosis factor-α (TNF-α) level in all participants
Summary
The maternal immune system must be immunologically tolerant to the semi-allograft fetus by suppressing the maternal alloreactive response against paternal antigens. It is well-known that regulatory T cell (Treg) is the CD4+ T cell that maintains maternal-fetal immune tolerance by preventing immune and autoimmune responses against self-antigens. T helper (Th) cells are effector cells that play an important role in modulating the activity of immune cells through the release of cytokines. The role that IL-17A plays in tolerating the allogeneic fetus is more controversial. IL17A expression in the human placenta may play a key role in the establishment of pregnancy. The passive transfer of purified Th17 cells into pregnant mice dramatically increases the proportion of fetal loss [11]
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