Could Mast Cells and Neutrophils Be Key Players in Multiple Sclerosis Activity? A New Genetic Study Says Maybe
Multiple sclerosis (MS) has long been recognized as a complex autoimmune disease where the body’s immune system attacks the central nervous system (CNS). But what makes some patients experience frequent relapses or worsening symptoms while others stay relatively stable? A recent Genome-Wide Association Study (GWAS) led by Antonino Giordano and colleagues offers intriguing new clues — and puts the spotlight on two unexpected immune cell types: mast cells and neutrophils.
Why This Study Matters
In recent years, major breakthroughs have uncovered dozens of genetic factors that influence a person’s risk of developing MS. But what about what happens after diagnosis? Specifically, what drives disease activity (DA) — the ups and downs of relapses, new brain lesions, or progression?
Objective: Identify genetic variants that are linked to disease activity in people with relapsing-remitting MS (RR-MS) — the most common MS type, where symptoms flare up and then improve.
Who Was Studied?
The researchers analyzed 790 Italian patients with RR-MS who were starting a first-line disease-modifying therapy. For each patient, they tracked whether or not they showed signs of disease activity (like relapses or MRI changes) over a 2-year follow-up. Patients were categorized based on the NEDA-3 (No Evidence of Disease Activity) status — a clinical standard for tracking MS control.
After removing low-quality genetic data and adjusting for population differences, 778 patients and over 600,000 genetic markers (called SNPs) were included in the final analysis.
What Did They Find?
Two genetic variants stood out — both located on chromosome 14:
rs1956932
rs17104242
These SNPs passed the strict statistical threshold for genome-wide significance, meaning they’re very unlikely to be false positives.
And here’s the key takeaway:
These variants were associated with a lower risk of disease activity over 2 years.
For rs1956932, the odds of having disease activity were reduced by 65% (OR=0.35).
For rs17104242, the risk was reduced by 64% (OR=0.36).
That’s a powerful protective effect.
What’s the Biology Behind It?
Digging deeper into the DNA neighborhood around these SNPs, the researchers found clues pointing to two enzymes:
Chymase-1
Cathepsin-G
Both are known for their roles in the activation and degranulation of mast cells and neutrophils — two types of immune cells.
Here’s why that’s interesting:
Mast cells, better known for their role in allergies, are also active in the nervous system and can influence blood-brain barrier (BBB) permeability.
Neutrophils are frontline soldiers of the immune system, capable of triggering widespread inflammation.
These cells may help shape how the immune system interacts with the CNS — potentially amplifying or suppressing disease activity in MS.
Why This Matters for MS Research (and Patients)
This is the first GWAS ever focused on MS disease activity, rather than just MS risk. And the findings suggest that genetic variation can influence how active the disease becomes, not just whether you get it in the first place.
Even more exciting, the discovery points to biological pathways — mast cell and neutrophil function — that haven’t been front and center in MS research before.
If these results are validated in future studies, they could open the door to:
New biomarkers to predict disease activity
New treatment targets aimed at calming overactive mast cells or neutrophils
Personalized treatment plans based on a patient’s genetic profile
A Note of Caution
As the authors themselves emphasize, this is a preliminary study. While the findings are statistically significant and biologically plausible, they still need to be:
Replicated in other populations
Studied in lab and animal models
Linked more directly to real immune function in MS patients
Wrapping Up
This GWAS adds a new piece to the MS puzzle. The identification of two protective genetic variants linked to mast cell and neutrophil regulation could shift how we understand — and eventually manage — disease activity in MS.
It's a reminder that even cells once overlooked in autoimmune diseases might hold important secrets.
Stay tuned: the future of personalized MS care might just involve taking a much closer look at your immune system’s first responders.
Disclaimer: This blog post is based on the provided research article and is intended for informational purposes only. It is not intended to provide medical advice. Please consult with a healthcare professional for any health concerns.
References:
Giordano A, Sorosina M, Clarelli F, et al. A Genome-Wide Association Study Highlights a Possible Involvement of Mast Cells and Neutrophils in Disease Activity in Multiple Sclerosis. Neurology. April 13, 2021; 96(15_supplement): 2289.
