Related Experiment Video
Updated: May 12, 2026

Methods for Quantitative Detection of Antibody-induced Complement Activation on Red Blood Cells
Published on: January 29, 2014
Complement split product C4d deposition in placenta in systemic lupus erythematosus and pregnancy-induced
Sachiko Minamiguchi1, Yoshiki Mikami, Naoki Nakajima
1Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan. minami@kuhp.kyoto-u.ac.jp
Insights
C4d immunohistochemistry in placentas may serve as a biomarker for adverse pregnancy outcomes in Systemic Lupus Erythematosus (SLE) and Pregnancy-Induced Hypertension (PIH). High C4d staining correlates with increased risk of intrauterine growth restriction (IUGR) and poorer disease control.
Area of Science:
- Immunohistochemistry
- Perinatal Medicine
- Reproductive Immunology
Background:
- Systemic lupus erythematosus (SLE) and pregnancy-induced hypertension (PIH) are linked to adverse pregnancy outcomes like premature delivery and intrauterine growth restriction (IUGR).
- Both SLE and PIH share placental histological findings and have associations with complement dysregulation during pregnancy.
Purpose of the Study:
- To investigate the diagnostic utility of C4d immunohistochemistry in placentas from pregnancies affected by SLE and PIH.
- To assess the correlation between C4d deposition and pregnancy complications in SLE and PIH.
Main Methods:
- C4d staining was performed on placental tissues from 26 SLE patients, 26 PIH patients, and 25 controls.
- Immunoreactivity was quantified using an H-score (0-300).
- Statistical analysis compared H-scores and correlated C4d levels with placental weight, birth weight, and gestational age.
Main Results:
- Placentas from SLE and PIH cases exhibited significantly higher C4d H-scores compared to controls (SLE: 38.3, PIH: 17.8, Control: 1.68).
- Linear C4d staining was observed on the syncytiotrophoblast membrane.
- C4d-high groups (50% SLE, 35% PIH) were significantly associated with lower placental weight, lower birth weight, and, in PIH cases, lower gestational age.
Conclusions:
- C4d immunohistochemistry is a potential biomarker for evaluating risks associated with IUGR in SLE and PIH pregnancies.
- C4d staining may aid in monitoring disease control during gestation for patients with SLE and PIH.
- This technique offers insights into the role of complement activation in adverse pregnancy outcomes.
Abstract:
Systemic lupus erythematosus (SLE) and pregnancy-induced hypertension (PIH) are related to premature delivery and intrauterine growth restriction (IUGR), and share histological findings of the placenta. Association with complement dysregulation has been reported in pregnancy for both disorders. The purpose of this study was to investigate the utility of C4d immunohistochemistry for placentas with SLE- and PIH-associated pregnancy. C4d staining was performed on paraffin-embedded tissue of placentas from 26 patients with SLE, 26 with PIH, and 25 control cases. We used the H-score with a range of 0-300 for the evaluation of C4d immunoreactivity. Placentas of SLE and PIH cases showed a higher H-score than control cases (average, SLE, 38.3 (P < 0.05); PIH, 17.8; control, 1.68), with linear staining on the membrane of syncytiotrophoblast. C4d-high groups comprised 50% (12/26) of SLE and 35% (9/26) of PIH cases, with H-scores ranging 14-270 and 15-170. C4d-high groups were significantly associated with low-placental weights and low birth weight in both SLE and PIH (P < 0.05), and lower gestational age (P < 0.05) in PIH cases. These results suggest that C4d might be utilized as a biomarker evaluating the subsequent risk for IUGR and disease control during the gestation period in these patients.
Related Concept Videos
Complement System
Transcytosis of IgG
IgG molecules from a mother undergo transcytosis starting around 13 weeks of gestation. The amount of IgG transferred and entering the fetal blood circulation increases with...
Teratogenicity
Hypersensitivity Reactions: Immune-Complex Reactions

