Risk Factors from Pregnancy to Adulthood in Multiple Sclerosis Outcome

Abstract

Multiple sclerosis (MS) is an autoimmune disease characterized by a robust inflammatory response against myelin sheath antigens, which causes astrocyte and microglial activation and demyelination of the central nervous system (CNS). Multiple genetic predispositions and environmental factors are known to influence the immune response in autoimmune diseases, such as MS, and in the experimental autoimmune encephalomyelitis (EAE) model. Although the predisposition to suffer from MS seems to be a multifactorial process, a highly sensitive period is pregnancy due to factors that alter the development and differentiation of the CNS and the immune system, which increases the offspring’s susceptibility to develop MS. In this regard, there is evidence that thyroid hormone deficiency during gestation, such as hypothyroidism or hypothyroxinemia, may increase susceptibility to autoimmune diseases such as MS. In this review, we discuss the relevance of the gestational period for the development of MS in adulthood.

Gestational hypothyroxinemia induces ASD-like phenotypes in behavior, proinflammatory markers, and glutamatergic protein expression in mouse offspring of both sexes

“…This observation aligns with earlier reports demonstrating that autistic children exhibit a heightened proportion of Th17 cells in comparison to Treg cells ( 65 ). These findings are also consistent with prior reports indicating that adult HTX-offspring exhibit a diminished tolerogenic capacity when confronted with the challenge of experimental autoimmune encephalomyelitis (EAE) ( 53 , 102 ). Complementary, their naïve T cells exhibited a reduced inclination to differentiate into the Treg cell phenotype which could be a possible contribution to the diminished Treg cell number observed ( 53 ).…”

Gestational hypothyroxinemia causes autistic-like behaviors, increases proinflammatory traits, and alters glutamatergic protein expression in mouse adult offspring of both sexes.

“…These findings harmonize with our prior reports indicating that adult HTX-offspring exhibit a diminished tolerogenic capacity when confronted with the challenge of experimental autoimmune encephalomyelitis (EAE) [56,99].…”

Genetic and early life factors influence on time-to-multiple sclerosis diagnosis: A UK Biobank study

“…31 This could be linked to maternal vitamin D deficiency, which represents a predisposal risk factor for MS development in pregnant women and their offspring. 32,33 In alignment with existing findings, 34,35 we also observed a positive additive interaction between high MS-PRS and a history of IM, with the strength of this interaction escalating with higher MS-PRS values. This is further supported by a recent research, which highlighted how individuals presenting high EBVantibodies levels are linked to a higher MS risk when in the presence of specific genetic variations, such as the presence of HLA-E*01:01 allele and genetic mutations in the KLRC2 gene (coding for a receptor protein expressed on natural killer cells).…”

“…31 This could be linked to maternal vitamin D deficiency, which represents a predisposal risk factor for MS development in pregnant women and their offspring. 32,33…”