TY - JOUR
T1 - Pathogenic roles of anti-C1q antibodies in recurrent pregnancy loss
AU - Ohmura, Kazumasa
AU - Oku, Kenji
AU - Kitaori, Tamao
AU - Amengual, Olga
AU - Hisada, Ryo
AU - Kanda, Masatoshi
AU - Shimizu, Yuka
AU - Fujieda, Yuichiro
AU - Kato, Masaru
AU - Bohgaki, Toshiyuki
AU - Horita, Tetsuya
AU - Yasuda, Shinsuke
AU - Sugiura-Ogasawara, Mayumi
AU - Atsumi, Tatsuya
N1 - Publisher Copyright:
© 2019 Elsevier Inc.
PY - 2019/6
Y1 - 2019/6
N2 - Recurrent pregnancy loss (RPL) is often considered idiopathic, however excessive complement activation has been observed in pregnancy related manifestations. Anti-C1q antibodies (anti-C1q) are associated with the activation of complement pathway in lupus patients, while it remains unclear in RPL. Firstly, we showed that both the prevalence and titre of anti-C1q were significantly higher in unexplained RPL than in healthy parous individuals. Secondly, we established the murine model of anti-C1q induced pregnancy loss using a monoclonal anti-mouse C1q antibody, JL-1. In mice treated with JL-1, high ratio of pregnancy loss and fetal growth restriction were frequently observed and complement activation occurred. C5a receptor (C5aR) blockade cancelled these pathogenic changes in mice treated with JL-1. In conclusion, our study reveals an association between the prevalence of anti-C1q and RPL. Additionally, our murine model has indicated that anti-C1q can induce reproductive failure, which might be ameliorated by therapy targeting the C5-C5aR axis.
AB - Recurrent pregnancy loss (RPL) is often considered idiopathic, however excessive complement activation has been observed in pregnancy related manifestations. Anti-C1q antibodies (anti-C1q) are associated with the activation of complement pathway in lupus patients, while it remains unclear in RPL. Firstly, we showed that both the prevalence and titre of anti-C1q were significantly higher in unexplained RPL than in healthy parous individuals. Secondly, we established the murine model of anti-C1q induced pregnancy loss using a monoclonal anti-mouse C1q antibody, JL-1. In mice treated with JL-1, high ratio of pregnancy loss and fetal growth restriction were frequently observed and complement activation occurred. C5a receptor (C5aR) blockade cancelled these pathogenic changes in mice treated with JL-1. In conclusion, our study reveals an association between the prevalence of anti-C1q and RPL. Additionally, our murine model has indicated that anti-C1q can induce reproductive failure, which might be ameliorated by therapy targeting the C5-C5aR axis.
KW - Anti-C1q autoantibody
KW - Complement activation
KW - Recurrent pregnancy loss
UR - http://www.scopus.com/inward/record.url?scp=85064320690&partnerID=8YFLogxK
U2 - 10.1016/j.clim.2019.04.005
DO - 10.1016/j.clim.2019.04.005
M3 - 学術論文
C2 - 30974291
AN - SCOPUS:85064320690
SN - 1521-6616
VL - 203
SP - 37
EP - 44
JO - Clinical Immunology
JF - Clinical Immunology
ER -