Abstract
Multiple sclerosis (MuS) is an autoimmune disease of the central nervous system characterized by neuroinflammation, neurodegeneration, and degradation of the myelin sheath. Epidemiological studies have shown that the female gender is more susceptible than the male gender to MuS development, with a female-to-male ratio of 2:1. Despite this high onset, women have a better prognosis than men, and the frequency of the relapsing phase decreases during pregnancy, while it increases soon after birth. Therefore, it is interesting to investigate hormonal fluctuations during pregnancy and whether they correlate with metabolic signatures. To gain a deeper inside into the biochemical mechanism of such a multifactorial disease, we adopted targeted metabolomics approaches for the determination of many serum metabolites in 12 pregnant women affected by MuS by mass spectrometry analysis. Our data show a characteristic hormonal fluctuation for estrogens and progesterone, as expected. They also highlight other interesting hormonal alterations for cortisol, corticosterone, 11-deoxycortisol, 4-androstene-3,17-dione, testosterone, and 17α-hydroxyprogesterone. Furthermore, a negative correlation with progesterone levels was observed for amino acids and for acylcarnitines, while an imbalance of different sphingolipids pathways was found during pregnancy. In conclusion, these data are in agreement with the characteristic clinical signs of MuS patients during pregnancy and, if confirmed, they may add an important tessera in the complex mosaic of maternal neuroprotection.
Highlights
Multiple sclerosis (MuS) is an autoimmune disease of the central nervous system (CNS) characterized by neuroinflammation, neurodegeneration, and loss of the myelin sheath of axons [1]
The multivariate analysis showed an unambiguous separation between the four clinical groups analyzed, already highlighting a trend of modulation during pregnancy
We have previously described an enhanced release of acid sphingomyelinase-enriched exosomes, which generated a lipidomic signature in the cerebrospinal fluid of MuS patients [15]
Summary
Multiple sclerosis (MuS) is an autoimmune disease of the central nervous system (CNS) characterized by neuroinflammation, neurodegeneration, and loss of the myelin sheath of axons [1]. In order to gain further insights into MuS during pregnancy, we started collecting and analyzing sera of MuS women in each trimester of pregnancy (First trimester: T1, Second trimester: T2, Third trimester: T3) and post-partum for studying metabolites levels. As it has been already discussed, estrogens and progesterone increase during pregnancy, in the third trimester, the time of greatest disease protection. Steroids quantification was integrated with that of other MuS-related metabolites, such as sphingolipids and ceramides, amino acids (AAs), free carnitine (C0), 35 acylcarnitines (ACCs), succinyl acetone (SA), 2 nucleosides, and 4 lysophospholipids (LPC)
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