Evidence of an altered cytokine profile in subsequent pregnancies after chronic histiocytic intervillositis treated with immunomodulatory and antithrombotic agents

<p dir="ltr">Chronic histiocytic intervillositis (CHI) is a placental lesion of unknown etiology where maternal macrophages accumulate in the intervillous space. Although rare, CHI is strongly associated with miscarriage and stillbirth and recurs in 25-100% of cases. Currently, diagnosis is only made following histopathological examination of the placenta. There are no antenatal biomarkers for CHI, although there are anecdotal reports of elevated serum alkaline phosphatase. This study aimed to explore the inflammatory profile of subsequent pregnancies following a CHI diagnosis treated with antithrombotic and immunomodulatory medication to establish potential factors linked with treatment success or disease recurrence for further investigation.</p><p dir="ltr">Serum and plasma were collected from pregnant women with a previous diagnosis of CHI (n=20) and gestational age-matched non-CHI controls (n=23) alongside matched placental tissue where available. Inflammatory markers and total and placental alkaline phosphatase were quantified via 54-plex immunoassay and electrophoresis, respectively. Pregnancies treated after CHI exhibited lower levels of interleukin (IL)-21, IL-22, IL-31 and basic fibroblast growth factor, whereas IL-8 was increased. No significant difference in total or placental alkaline phosphatase was evident between groups, and levels were not related to disease recurrence.</p><p dir="ltr">The observed reductions in circulating cytokines are likely an effect of medication; however, the pro-inflammatory cytokine IL-8 was elevated despite immunomodulatory treatment. Further investigation of these markers in untreated pregnancies and those receiving different regimens is warranted to determine their potential associations with disease or treatment success. Our data agrees with those of other studies suggesting that elevated alkaline phosphatase is not a reliable biomarker of CHI.</p>