TY - JOUR

T1 - The pathogenic role of circulating Hashimoto's Thyroiditis-derived TPO-positive IgG on fetal loss in naïve mice

AU - Borodina, Elena

AU - Katz, Itai

AU - Antonelli, Alessandro

AU - Gzgzyan, Alexander M.

AU - Dzhemlikhanova, Liailia Kh

AU - Ostrinsi, Yuri

AU - Niauri, Dariko

AU - Khizroeva, Jamilya

AU - Bitsadze, Victoria

AU - Makatsariya, Alexander

AU - Tincani, Angela

AU - Nalli, Cecilia

AU - Churilov, Leonid P.

AU - Shovman, Ora

AU - Halpert, Gilad

AU - Blank, Miri

AU - Shoenfeld, Yehuda

AU - Amital, Howard

N1 - Funding Information: This work was supported by the grant of the Government of the Russian Federation for the state support of scientific research carried out under the supervision of leading scientists, agreement 14.W03.31.0009. Publisher Copyright: © 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd Copyright: Copyright 2020 Elsevier B.V., All rights reserved.

PY - 2020/9/20

Y1 - 2020/9/20

N2 - 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 <.001) in comparison with 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 =.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.

AB - 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 <.001) in comparison with 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 =.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.

KW - anti-TPO

KW - murine fetal loss

KW - reproductive failure

KW - AUTOIMMUNE-THYROIDITIS

KW - PREGNANCY

KW - DISEASE

KW - WOMEN

UR - http://www.scopus.com/inward/record.url?scp=85091086312&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/27e6b90a-dcf4-38fb-8e50-fb7f03635963/

U2 - 10.1111/aji.13331

DO - 10.1111/aji.13331

M3 - статья

C2 - 32893404

JO - Early pregnancy : biology and medicine : the official journal of the Society for the Investigation of Early Pregnancy

JF - Early pregnancy : biology and medicine : the official journal of the Society for the Investigation of Early Pregnancy

SN - 8755-8920

M1 - 13331

ER -