Decline in Number of Elevated Blood CD3⁺ CD56⁺ NKT Cells in Response to Intravenous Immunoglobulin Treatment Correlates with Successful Pregnancy

Abstract

Elevated NKT cells in recurrent pregnancy loss or implantation failure can be ameliorated with IVIG treatment, and result in successful pregnancy. Assay of NKT cell numbers may identify patients who are more likely to benefit from IVIG therapy and merits further examination in randomized phase II studies.

CD200-dependent and nonCD200-dependant pathways of NK cell suppression by human IVIG

“…In IVIG treatment of recurrent pregnancy failure, a suppression of blood NKT cells rather than NK cells was suggested as more relevant [4]. It remains to be determined how IVIG suppresses NKT cells, if this is CD200R-dependent in part, and if the effect is indirect rather than direct.…”

“…It remains to be determined how IVIG suppresses NKT cells, if this is CD200R-dependent in part, and if the effect is indirect rather than direct. Indeed, in the in vivo study of IVIG suppression of NKT as a correlate of pregnancy success, some patients proved resistant to suppression [4]. This was not attributable to use of a less active product (e.g.…”

“…There is also empirical evidence for benefit in patients with recurrent spontaneous abortion if secondary or associated with autoantibodies or elevated natural killer (NK)-lineage cells in blood [2][3][4]. In vitro fertilization failure may also be prevented in patients who have immune abnormalities [2].…”

“…In vitro fertilization failure may also be prevented in patients who have immune abnormalities [2]. Suppression of blood NK cell activity has been proposed as an important effect, and different IVIGs may differ in potency both in vitro and in vivo [3][4][5]. However, the mechanism of IVIG suppression of NK-type cells is uncharacterized.…”

Immunogenetic contributions to recurrent pregnancy loss

“…One randomized study noted no difference in birth outcomes of patients taking IVIG versus placebo [135]. However, there is evidence that IVIG does reduce levels of NK and NKT [136,137].…”