The Role of NK Cells in the Autoimmune Thyroid Disease-associated Pregnancy Loss

Abstract

Pregnancy loss is a frequent event. Autoimmune thyroid disorders and altered natural killer (NK) cell functions are two distinct risk factors, which independently could induce adverse pregnancy outcome. Thyroid autoimmunity has been an object of increased attention by investigators in the context of pregnancy loss. Peripheral NK cells and uNK cells comprise distinct cell populations in terms of phenotype and function but they play an important role in the course of a normal human pregnancy via several potential functions. In autoimmune thyroid diseases, several abnormalities of killer cell activity have been described. The functional defects involving NK maturation and/or functional activation observed in Graves' disease patients could independently influence the reproductive outcome. This suggestion needs extensive investigation and could be important for the therapeutical approach in preventing pregnancy loss in patients with thyroid autoimmunity.

Pathogenesis of infertility and recurrent pregnancy loss in thyroid autoimmunity

“…These observations suggest that there are activated T cells in the uteri of women with anti-thyroid antibodies that secrete cytokines that hamper successful pregnancy [22,23,26,27]. These adverse effects can be mediated directly through T cells or indirectly through other cells, such as natural killer cells [28]. Therefore, according to this hypothesis thyroid autoantibodies serve as peripheral markers of abnormal T cell function, and not necessarily abnormal pathogenic antibodies per se which are responsible for pregnancy loss [26,27,29,30].…”

Identification and management of conditions detrimental to IVF outcome

“…68 Thyroid autoimmunity (where immune antibodies destroy cells in the thyroid gland) affects 5-10% of women of childbearing age. 69 It is the biggest cause of hypothyroidism. 69 …”

HELLP syndrome: a complication or a new autoimmune syndrome?

“…Decreased GSH levels can modulate the immune response influencing the proliferation of NK cells [24]. NK cells are the predominant leukocyte population in the endometrium at the time of implantation and in early pregnancy [25,26]. The role of NK cells has been reported to be immunosurveillance; these cells may also mediate the angiogenesis necessary for continuation of the pregnancy or for the remodeling of the spiral arteries to uteroplacental arteries [24].…”