Complement split product C4d deposition in placenta in systemic lupus erythematosus and pregnancy‐induced hypertension

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.

Increased risk of systemic lupus erythematosus in pregnancy-induced hypertension

“…A study conducted by Minamiguchi et al [21] indicated that the degree of C4d immunoreactivity was associated with low placental weight and histological placental abnormalities among individuals with PIH, as well as among those with SLE. Activation of the complement cascade may result in placental dysfunction in cases of PIH and in cases of SLE.…”

“…It is possible that alterations in the immune system that are associated with preterm delivery may be implicated in an increased risk for developing autoimmune diseases. For example, C4d immunoreactivity is related to low placental weight and preterm birth [21,22] and is also involved in the pathogenesis of SLE. [21] Interestingly, a population-based cohort study indicated that nulliparous women and 1-child mothers display a markedly increased risk for developing SLE.…”

“…PIH and SLE share histological findings of the placenta. [21–23] In addition, both diseases are related to premature delivery and intrauterine growth restriction. [24–26] Moreover, preeclampsia is associated with lupus flares.…”

The Important Roles of C4d in Systemic Lupus Erythematosus

“…Diffuse C4d staining at the feto-maternal interface was present almost exclusively in patients with SLE and/or APS and was related to intrauterine fetal death [37]. Dramatically increased immunohistochemistry staining of C-4d was statistically associated with low-placental weights and low birth weight in SLE patients [38].…”

“…Adverse events during pregnancy [35][36][37] Renal tissue Related to the presence of microthrombosis and histopathological classification of lupus nephritis [38,42] No relationship with disease activity, histological activity and chronicity of lupus nephritis [41,43,44] …”