title: Intravenous Immunoglobulin Suppresses Abortion Relates to an Increase in the CD44bright NK Subset in Recurrent Pregnancy Loss Model Mice.
abstract: Recurrent pregnancy loss (RPL), which mostly is of unknown etiology (unexplained RPL, uRPL), is defined as three or more consecutive spontaneous abortions. Some women with uRPL display a higher fraction and cytotoxicity of natural killer (NK) cells in the periphery and endometrium. Therefore, some uRPL cases have been explained by autoimmune abnormalities. The efficacy of intravenous immunoglobulin (IVIg) for uRPL has been confirmed in several clinical trials; however, its mechanism remains unknown, mainly because the abortion mechanism remains to be elucidated. In the present study, we analyzed the mechanisms of both abortion and IVIg action using a uRPL mouse model in which abortion was induced by lipopolysaccharide injection. IVIg attenuated the abortion rate in the uRPL model mice. The suppressive effect of IVIg was maximized by high dose administration early after lipopolysaccharide injection. Specifically, we discovered the presence of two distinct uterine NK (uNK) subsets: CD44(bright) and CD44(mid) In uRPL model mice, we observed an increase in the number of CD44(bright) uNK cells, while the CD44(mid) uNK subset remained unchanged. Furthermore, when abortion was reduced by IVIg administration, the cell number of the CD44(bright) uNK subset did not increase, which might allow differentiating pathological from normal uNK cells based on CD44 expression. Based on these results, we propose not only an effective administration protocol of IVIg to the uRPL model mice, but also a novel mechanism of abortion related to the increase in the CD44(bright) subset and of IVIg, which suppresses the increase of the CD44(bright) subset.
authors.affiliation: Central Research Laboratory, Japan Blood Products Organization, Kobe, Japan tanaka-jun@jbpo.or.jp.
authors.forename: Jun
authors.initials: J
authors.lastname: Tanaka
authors.affiliation: Central Research Laboratory, Japan Blood Products Organization, Kobe, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Kitashoji
authors.affiliation: Central Research Laboratory, Japan Blood Products Organization, Kobe, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Fukunaga
authors.affiliation: Central Research Laboratory, Japan Blood Products Organization, Kobe, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Kashihara
authors.affiliation: Central Research Laboratory, Japan Blood Products Organization, Kobe, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nakano
authors.affiliation: Central Research Laboratory, Japan Blood Products Organization, Kobe, Japan.
authors.forename: Akihito
authors.initials: A
authors.lastname: Kamizono
mesh_terms: D000026:Abortion, Habitual / Q000378:metabolism / Q000517:prevention & control*; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D018960:Hyaluronan Receptors / Q000378:metabolism*; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use*; D007694:Killer Cells, Natural / Q000378:metabolism*; D051379:Mice; D011374:Progesterone / Q000097:blood; D013154:Spleen / Q000378:metabolism; D014599:Uterus / Q000378:metabolism
chemical_list: D018960:Hyaluronan Receptors; D016756:Immunoglobulins, Intravenous; D011374:Progesterone
keywords: IVIg; NK cells; abortion; recurrent pregnancy loss