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Mast cell and neutrophil involvement in MS activity

AAN 2021

Preliminary results of a genome-wide association study (GWAS) demonstrate a possible involvement of mast cells and neutrophils in disease activity of patients with relapsing-remitting multiple sclerosis (MS). These results may provide important knowledge on mechanisms underlying disease activity and could lead to future therapeutic developments.

Evidence on the genetic basis of the broad heterogeneity in the clinical spectrum of MS is still limited. Italian researchers performed the first GWAS that targeted disease activity in MS [1]. A total of 790 patients with confirmed relapsing-remitting MS were followed for 2 years from the moment they started a first-line disease-modifying treatment. Disease activity was assessed according to No-Evidence/Evidence of Disease Activity-3 (NEDA/EDA-3) status. After quality controls, 778 patients and 607,864 single nucleotide polymorphisms (SNPs) were subjected to the GWAS.

Two SNPs at chromosome 14 passed the threshold for genome-wide significance: rs1956932 and rs17104242. These polymorphisms were found to protect EDA status at 2 years (OR 0.35 and 0.36, respectively). For 3 other SNPs –also located at chromosome 14– an association was found that suggested protection from disease activity, safeguarding NEDA status. There is a possible involvement of the chymase-1 (CMA-1) and cathepsin-G (CTSG) pathways. These pathways are involved in the activity and degranulation of mast cells and neutrophils, respectively. Neutrophils and mast cells have been associated with disease mechanisms in MS, such as the regulation of the blood-brain barrier, inflammatory response, and evoking a CNS-directed immune response through peripheral activation.

  1. Giordano A, et al. A Genome-Wide Association Study Highlights a Possible Involvement of Mast Cells and Neutrophils in Disease Activity in Multiple Sclerosis. S11.002, AAN 2021 Virtual Congress, 17-22 April.

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