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Multiplexed Fluorescent Immunohistochemical Staining of Four Endometrial Immune Cell Types in Recurrent Miscarriage
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Increased complement C4d deposition at the maternal-fetal interface in unexplained recurrent miscarriage.

Tess Meuleman1, Danielle Cohen2, Godelieve M J S Swings3

  • 1Department of Obstetrics, Leiden University Medical Center, 2300 RC Leiden, the Netherlands; Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2300 RC Leiden, the Netherlands.

Journal of Reproductive Immunology
|January 14, 2016
PubMed
Summary

Complement activation, indicated by C4d deposition, is elevated in women with unexplained recurrent miscarriages. This finding suggests a potential role for aberrant anti-fetal immunity in pregnancy loss.

Keywords:
C4dClassical complement systemRecurrent miscarriage

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Area of Science:

  • Reproductive Immunology
  • Complement System Biology

Background:

  • C4d deposition signifies antibody-mediated complement activation and is a marker for antibody-mediated rejection.
  • The role of complement activation, specifically C4d deposition, in unexplained recurrent miscarriage remains unclear.

Purpose of the Study:

  • To investigate the presence and significance of C4d deposition in the products of conception from women experiencing unexplained recurrent miscarriages.

Main Methods:

  • A case-control study included products of conception from women with unexplained recurrent miscarriage (cases), sporadic miscarriage (control 1), and elective abortion (control 2).
  • Immunohistochemical staining was used to detect C4d deposition, which was then semi-quantitatively scored.

Main Results:

  • C4d deposition was observed in 40.0% of unexplained recurrent miscarriage cases, compared to 27.3% in sporadic miscarriage and 10.0% in elective abortion controls (p=0.020).
  • Increased C4d deposition was found at the maternal-fetal interface in women with unexplained recurrent miscarriage.

Conclusions:

  • Elevated C4d deposition in unexplained recurrent miscarriage suggests a potential role for aberrant anti-fetal immunity.
  • Further research into the pathogenic mechanisms could lead to novel therapeutic strategies for recurrent miscarriage.