The pathogenic role of circulating Hashimoto's Thyroiditis-derived TPO positive IgG on fetal loss in naïve mice

Elena Borodina, Itai Katz, Alessandro Antonelly, Alexander M. Gzgzyan, Liailia Kh. Dzhemlikhanova, Yuri Ostriski, Dariko Niauri, Khizroeva Jamilya, Victoria Bitsadze, Alexander Makatsariya, Angela Tincani, Cecilia Nalli, Leonid P Churilov, Ora Shovman, Gilad Halpert, Miri Blank, Yehuda Shoenfeld, Howard Amital

Результат исследований: Научные публикации в периодических изданияхстатья

Аннотация

PROBLEM: Antibody-mediated-autoimmune diseases such as autoimmune thyroid diseases (ATD), systemic-lupus-erythematosus (SLE) and antiphospholipid-syndrome (APS), often are associated with 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 (anti-TPO). In retrospective study of sera analyses in patients with Hashimoto's thyroiditis, all patients had mainly elevated circulating anti-TPO autoantibodies.

AIM: We assessed the potential of human anti-TPO highly positive IgG, derived from patients with Hashimoto's thyroiditis sera associated with complications of pregnancy, to cause directly complications of pregnancy in murine model.

METHOD OF STUDY: Naïve ICR female mice, infused intravenously with 100 µg of anti-TPO positive 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, we observed embryos small for date in the mice passively transferred with anti-TPO positive IgG, exemplified by reduced weight of embryos and placentae (p=0.001). Histopathological examination revealed delay in fetal development in 50% cases of anti-TPO positive 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 anti-TPO positive IgG samples.

CONCLUSION: The current study shows in the first time, a direct proof of concept, on the association of human TPO positive IgG from Hashimoto's thyroiditis patients on fetal loss induction in murine model.

Язык оригиналаанглийский
Номер статьиe13331
ЖурналAmerican Journal of Reproductive Immunology
СостояниеЭлектронная публикация перед печатью - 6 сен 2020

Предметные области Scopus

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