Background and Aims

Antibody-mediated-autoimmune-diseases such as autoimmune thyroid diseases (ATD), systemic-lupus-erythematosus (SLE) and antiphospholipid-syndrome (APS), often are associated with abnormalities of fetal development and recurrent fetal loss. One of the ATD is Hashimoto's thyroiditis which recently showed association with complications of pregnancy with increased levels of circulating autoantibodies reactive with epitopes on thyroid tissue such as thyroid peroxidase (aTPO). In retrospective study of sera analyses in patients with Hashimoto's thyroiditis, all patients had elevated circulating aTPO autoantibodies, whereas about 50% of patients with circulating autoantibodies targeting thyroglobulin or thyroid stimulating hormone antibodies (anti-TSH).
We assessed the potential of human anti-TPO highly positive IgG, derived from patients with Hashimoto's thyroiditis sera, to cause directly complications of pregnancy in murine experimental model.

Methods

Naïve ICR female mice, were infused with aTPO, or control IgG. Pregnancy development was followed.

Results

Infusion of aTPO-IgG showed increased fetal loss and embryo small for date, (p<0.001) in comparison to mice passively transferred with commercial IgG, or PBS. Moreover, the aTPO-IgG subjected mice, showed reduced weight of embryos and placentae (p=0.001). Histopathological examination revealed delay in fetal development in 50% cases of aTPO- IgG treated mice. Importantly, pathological changes in the transition zone, state of glycogen cells and significant structural changes in the labyrinth part of placenta were observed in all aTPO-IgG samples.

Conclusions

Our study shows for the first time, a direct proof of concept, on the pathogenic role of aTPO-IgG in induction of murine fetal loss, association of fetal loss in patients with Hashimoto's thyroiditis.