MicroRNA profile in normal pregnancies with isolated low IgM anticardiolipin levels.

Abstract: Moderate and high levels of anticardiolipin antibodies (aCL) are associated with pregnancy-related complications, thrombosis, and other cardiovascular diseases. However, the clinical impact of isolated low IgM aCL levels on pregnancy outcomes has not yet been demonstrated in large-scale analyses. This study aimed to evaluate whether isolated low aCL levels induce epigenetic changes at early stages of gestation in otherwise normally ongoing pregnancies. The expression of 29 microRNAs linked to adverse obstetric outcomes and cardiovascular risk was assessed in 40 singleton normal term pregnancies with isolated low IgM aCL levels (IgM aCL <40 MPL units, IgG aCL negative) and 75 gestational-age-matched aCL-negative controls, using reverse transcription real-time polymerase chain reaction. Two microRNAs (miR-100-5p and miR-199a-5p) were upregulated, and seven (miR-130b-3p, miR-133a-3p, miR-145-5p, miR-155-5p, miR-210-3p, miR-342-3p, and miR-574-3p) were downregulated in normal term pregnancies with isolated low IgM aCL levels. After adjusting for maternal age, pre-pregnancy BMI, smoking, autoimmune disease, inherited thrombophilia, history of precancerosis, and ART conception, dysregulation of miR-133a-3p, miR-145-5p, and miR-574-3p remained statistically significant. Logistic regression (enter and backward methods) achieved very good performance in differentiating between cases and controls (areas under curve 0.917 and 0.908, respectively; 77.50% sensitivities at 10% false-positive rate; 86.96% accuracies). Using the multilayer perceptron, a type of artificial neural network, multiple models based on nine microRNAs were constructed. Some of them had better overall performance than the logistic regression approach. Isolated low IgM aCL positivity can adversely modify the epigenetic profile, which under additional unfavorable conditions may lead to pregnancy complications and increased cardiovascular risk. Lay summary: Some women have certain antibodies in their blood called aCL (anticardiolipin antibodies). These antibodies can sometimes be linked to pregnancy complications or a higher risk of heart disease. This study explored whether low levels of one type of these antibodies (called IgM aCL) early in pregnancy might still affect the body in ways that might matter later. We compared pregnant women with low levels of these antibodies to those without the antibodies and examined microRNAs - tiny molecules that help control cell activity - in their blood. Even low antibody levels were linked to small changes in microRNAs during the first trimester. Some of these changes resembled patterns seen in pregnancies that later develop complications or in people with increased cardiovascular risk. These findings do not mean that low antibody levels always cause problems. Instead, they suggest that such antibodies may slightly increase vulnerability, especially when combined with other risk factors.