The immune checkpoint pathophysiology of depression and chronic fatigue syndrome due to preeclampsia: focus on sCD80 and sCTLA-4

Abstract Background Neuropsychiatric disorders in preeclampsia (PE) women are prevalent and worsen PE outcome. Immune-related biomarkers including soluble sCD80 and cytotoxic T-lymphocyte antigen-4 (sCTLA-4) are not well studied in relation to depression, anxiety, and chronic fatigue due to PE. Methods The aim is to study serum immune-inflammatory biomarkers of PE and delineate their associations with the Hamilton Depression (HAMD), Anxiety (HAMA), and Fibro-Fatigue (FF) rating Scale scores. sCD80, sCTLA-4, vitamin D, granulocyte-macrophage colony-stimulating factor, zinc, copper, magnesium, and calcium were measured in 90 PE compared with 60 non-PE pregnant women. Results PE women show higher depression, anxiety and FF rating scale scores as compared with control women. sCTLA-4, sCD80, and copper were significantly higher and zinc, magnesium, and calcium significantly lower in PE women than in controls. Multiple regression analysis showed that around 55.8%-58.0% of the variance in the HAMD, HAMA and FF scores was explained by the regression on biomarkers; the top 3 most important biomarkers were sCTLA-4, sCD80, and vitamin D. The sCTLA-4/sCD80 ratio was significantly and inversely associated with the HAMD/HAMA/FF scores. We found that around 70% of the variance in systolic blood pressure could be explained by sCTLA-4, vitamin D, calcium, and copper. Conclusions The findings underscore that PE and depression, anxiety, and chronic fatigue symptoms due to PE are accompanied by activation of the immune-inflammatory response system. More specifically, disbalances among soluble checkpoint molecules seem to be involved in the pathophysiology of hypertension and neuropsychiatric symptoms due to PE.