Preliminary results of a genome-wide-association study (GWAS) show a possible involvement of mast cells and neutrophils in the disease activity of relapsing-remitting MS patients [1]. These results provide important knowledge on mechanisms underlying disease activity and could lead to future therapeutic developments.


The pathological foundations for disease activity in MS are largely unknown and heterogeneous. Dr Antonio Giordano presented the study design and findings of the first GWAS targeting disease activity in MS [1]. Italian patients with confirmed RRMS (n=790) were followed for 2 years from the beginning of a first-line disease-modifying treatment. Disease activity was monitored by NEDA/EDA 3 status and whole-genome genetic data had to be available for inclusion. After quality control, 778 patients and 607,864 SNPs were subjected to the GWAS. The preliminary results demonstrated that 2 SNPs passed the genome-wide significant association threshold and 3 other SNPs passed the suggestive association threshold, all located at chromosome 14. Further analysis showed that these SNPs are safeguarding the NEDA status of the patients. Dr Giordano explained that the findings are possible linked to 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. Moreover, mast cells have been located in demyelinating events of MS patients. In conclusion, the first GWAS of disease activity in MS patients identified 2 SNPs with a potential protective role, possibly related to mast cell and neutrophil expression. Larger studies have to confirm whether these results could lead to future therapeutic developments.


  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.