Genetic and environmental factors influence MS in monozygotic twin pairs

According to a recent study published in Nature. Twins with MS showed a shift in their compartment from circulating monocytes to inflammatory monocytes.

Genetic risk factors and environmental triggers of MS have indefinite interactions. The etiology of MS remains essentially unknown. Therefore, “investigating how genetic predisposition and environmental triggers shape the interactions of individual immune cells is essential to understanding the pathophysiology of autoimmune diseases, including MS,” the researchers explained.

The aim of the present study was to understand the genetic and environmental predisposition of discordant monozygotic twin pairs for MS, meaning that both siblings had the same genetic and environmental risks in early life, but only one brother had MS.


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In their analysis, the researchers looked at the peripheral immune signature of 61 pairs of discordant monozygotic twins for MS. This group was part of the MS TWIN study at the Institute of Clinical Neuroimmunology at the LMU Klinikum in Munich, Germany. Pairs of twins were interviewed and underwent neurological examination, blood sampling and MRI between May 2012 and May 2020.

The diagnosis of MS was confirmed by medical records and MRIs, then the participants were randomized and then analyzed by mass cytometry. Cell indexing analysis of transcriptomes and epitopes (CITE-seq) of the myeloid compartment was also performed.

The researchers integrated data on the immune profiles of pairs of healthy monozygotic and dizygotic twins, which allowed them to estimate that the variance of the IL-2 receptor alpha chain is largely determined by early environmental influences. shared and genetic.

In the twins, higher sensitivity to specific cytokines led to higher T cell activation which may have infiltrated the central nervous system and potentially caused tissue damage and neurological deficits.

“Expanding helper T cells in MS twins, which were also elevated in non-twin MS patients, arose independent of individual genetic makeup. These cells expressed central nervous system receptors, exhibited dysregulated CD25 (CD25 represents a major MS risk genetic allele)–IL-2 axis, and their proliferative capacity is positively correlated with MS severity,” the researchers wrote.

Study limitations included a larger fraction of younger twins with less severe disease severity; participants with more than one family member with MS may have introduced a higher family risk bias; heterogeneity in age, disease course and treatment; disease-modifying therapy for the twin with MS; and may include a mass cytometry analysis that was performed in two independent cycles, but was not repeated due to limited valuable sample.

“The observation that some of the findings revealed in this study have already been reported in cross-sectional studies of MS…while other features have demonstrated opposite trends to what has been previously described, underscores the importance of discerning the genetic predisposition for environmentally induced alterations in MS,” the researchers concluded.

Reference

Ingelfinger F, Gerdes LA, Kavaka V, et al. Twin study reveals non-inherited immune disturbances in multiple sclerosis. Nature. Published online February 16, 2022. doi:10.1038/s41586-022-04419-4

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