Longitudinal assessment of HLA and MIC-A antibodies in uneventful pregnancies and pregnancies complicated by preeclampsia or gestational diabetes

Abstract

The significance of antibodies directed against paternal epitopes in the context of obstetric disorders is discussed controversially. In this study anti-HLA and anti-MIC-A antibodies were analysed in sera of women with uneventful pregnancy (n = 101), preeclampsia (PE, n = 55) and gestational diabetes (GDM, n = 36) using antigen specific microbeads. While two thirds of the women with uneventful pregnancy or GDM were HLA and MIC-A antibody positive in gestational week 11 to 13 with a modest increase towards the end of pregnancy, women with PE showed an inverse kinetic: 90% were HLA antibody positive in gestational week 11 to 13 and only 10% showed HLA reactivities at the end of the pregnancy. HLA antibody binding strength was more pronounced in gestational week 14 to 17 in patients with PE compared to women with uneventful pregnancy (maximum median fluorescence intensity of the highest ranked positive bead 7403, IQR 2193–7938 vs. 1093, IQR 395–5689; p = 0.04) and was able to predict PE with an AUC of 0.80 (95% CI 0.67–0.93; p = 0.002). Our data suggest a pathophysiological involvement of HLA antibodies in PE. HLA antibody quantification in early pregnancy may provide a useful tool to increase diagnostic awareness in women prone to develop PE.

Biologic mechanisms and clinical consequences of pregnancy alloimmunization

“…2 However, recent studies using more-sensitive single-antigen beads (SABs) demonstrate that 50% to 75% of women have detectable anti-HLA antibody at the time of delivery. 5,6 While studies that reveal the natural history of this antibody after pregnancy are limited, investigations that have assessed the first postpartum year suggest that the frequency of women with detectable antibody increases within 90 days of delivery but then decreases over the next 1 to 2 years. 5,6 While studies that reveal the natural history of this antibody after pregnancy are limited, investigations that have assessed the first postpartum year suggest that the frequency of women with detectable antibody increases within 90 days of delivery but then decreases over the next 1 to 2 years.…”

“…3,4 Surveillance studies indicate that many women develop this antibody in the first trimester, and this frequency increases over the course of gestation. 4,5 The longest study, which consecutively surveyed women for up to 2 years postpartum, suggests that anti-HLA antibody will disappear in approximately 50% of women. 4,5 The longest study, which consecutively surveyed women for up to 2 years postpartum, suggests that anti-HLA antibody will disappear in approximately 50% of women.…”

“…7 While these studies suggest that the frequency of detectable antibody decreases significantly within just a few years of pregnancy, other epidemiologic evidence suggests that the incidence of this antibody can decrease over a much more prolonged period of time (ie, decades). 3,5,8 While estimates vary, the prevalence of detectable anti-HLA antibody appears to double between the first and second pregnancies (first pregnancy 11-33% vs second pregnancy 22-62% 5,8 ). 3,5,8 While estimates vary, the prevalence of detectable anti-HLA antibody appears to double between the first and second pregnancies (first pregnancy 11-33% vs second pregnancy 22-62% 5,8 ).…”

“…3,4 Surveillance studies indicate that many women develop this antibody in the first trimester, and this frequency increases over the course of gestation. 5,6 While studies that reveal the natural history of this antibody after pregnancy are limited, investigations that have assessed the first postpartum year suggest that the frequency of women with detectable antibody increases within 90 days of delivery but then decreases over the next 1 to 2 years. 4,5 The longest study, which consecutively surveyed women for up to 2 years postpartum, suggests that anti-HLA antibody will disappear in approximately 50% of women.…”

“…5,6 While studies that reveal the natural history of this antibody after pregnancy are limited, investigations that have assessed the first postpartum year suggest that the frequency of women with detectable antibody increases within 90 days of delivery but then decreases over the next 1 to 2 years. 4,5 The longest study, which consecutively surveyed women for up to 2 years postpartum, suggests that anti-HLA antibody will disappear in approximately 50% of women. 7 While these studies suggest that the frequency of detectable antibody decreases significantly within just a few years of pregnancy, other epidemiologic evidence suggests that the incidence of this antibody can decrease over a much more prolonged period of time (ie, decades).…”