Multivariate analysis of cytokine profiles in pregnancy complications

Problem: The immunoregulation to tolerate the semiallogeneic fetus during pregnancy includes a harmonious dynamic balance between anti- and pro-inflammatory cytokines. Several earlier studies reported significantly different levels and/or ratios of several cytokines in complicated pregnancy as compared to normal pregnancy. However, as cytokines operate in networks with potentially complex interactions, it is also interesting to compare groups with multi-cytokine data sets, with multivariate analysis. Such analysis will further examine how great the differences are, and which cytokines are more different than others. Methods: Various multivariate statistical tools, such as Cramer test, classification and regression trees, partial least squares regression figures, 2-dimensional KolmogorovSmirmov test, principal component analysis and gap statistic, were used to compare cytokine data of normal vs anomalous groups of different pregnancy complications. Results: Multivariate analysis assisted in examining if the groups were different, how strongly they differed, in what ways they differed and further reported evidence for subgroups in 1 group (pregnancy-induced hypertension), possibly indicating multiple causes for the complication. Conclusion: This work contributes to a better understanding of cytokines interaction and may have important implications on targeting cytokine balance modulation or design of future medications or interventions that best direct management or prevention from an immunological approach.