Genes and the Brain: How HLA Genotyping is Shaping the Future of Multiple Sclerosis Care

A landmark review by Dr. Petros Stamatelos and Dr. Maria Anagnostouli explores how variations in HLA genes—especially the notorious DRB1*15:01 allele—can influence nearly every aspect of MS. From the disease’s onset and severity to how well patients respond to medications, your immune system’s genetic “fingerprint” plays a central role.

What is MS and Why Does Genetics Matter?
Multiple sclerosis is a chronic, inflammatory disease where the immune system mistakenly attacks the central nervous system, damaging the protective myelin sheath around nerve fibers. It affects around 2 million people worldwide and is especially common in Europe.

While the cause of MS remains mysterious, it's widely accepted that both environmental and genetic factors contribute. The most powerful genetic influence? The HLA system, particularly class II genes like HLA-DRB1.

HLA-DRB1*15:01 – The Genetic “Smoking Gun” in MS
Among dozens of HLA gene variants, DRB1*15:01 stands out as the strongest known genetic risk factor for MS. Carrying one copy of this allele increases your MS risk two to threefold—and two copies increase it even more.

But it’s not just about risk. DRB1*15:01 also:

Is more common in women with MS

Is linked to earlier disease onset

Is associated with worse spinal cord inflammation and brain volume loss

Correlates with more severe cognitive decline

It's like this gene doesn’t just light the fire—it adds fuel to it.

Gene Meets Environment: Smoking, Vitamin D, and Viruses
The plot thickens when we look at gene-environment interactions. This research highlights how certain environmental exposures have amplified effects when paired with risky HLA genes.

Vitamin D: Low vitamin D levels increase MS risk, especially in people with DRB1*15:01. A vitamin D response element was even found in this gene’s promoter region—direct biological proof of interaction.

Smoking: Smokers with DRB115:01 and no protective HLA-A02 allele had a 13.5 times higher MS risk compared to non-smokers without these risk genes.

Epstein-Barr Virus (EBV): Nearly all MS patients are EBV-positive, and the link is stronger in those with DRB1*15:01.

Beyond Risk: Genes Predict Disease Course and Cognitive Decline
Genes don’t just influence whether you’ll get MS—they can also shape how it unfolds. For example:

HLA-DRB1*15:01 is linked to faster disability progression and more severe cognitive impairment.

Other HLA alleles like *11 and *14 may protect against MS or lead to milder forms.

Even brain scans show a difference. DRB115:01 is associated with more lesions and brain atrophy on MRI, while HLA-B44 may offer radiological protection.

Personalized Medicine: Tailoring Treatment by HLA Type
This is where things get truly futuristic. Your HLA genotype can predict how you’ll respond to key MS treatments like:

Glatiramer Acetate (GA): DRB1*15:01 carriers tend to respond better.

Interferon-beta (IFN-β): DRB115:01 and DRB104 alleles are linked to increased risk of forming neutralizing antibodies, reducing drug effectiveness.

Natalizumab: Certain HLA types (like DRB1*13 and 14) are associated with allergic reactions; DRB115 may be protective.

In other words, knowing your HLA type could help avoid ineffective drugs and minimize side effects. Not Just MS: A Role in Other Demyelinating Diseases
The HLA system also helps distinguish MS from related diseases like:

Neuromyelitis Optica (NMO): Linked to HLA-DPB105:01 in Asians and DRB103 in Caucasians, not DRB1*15:01.

Acute Disseminated Encephalomyelitis (ADEM): Associated with different HLA alleles like DRB1*01 and *17, especially in children.

This suggests different underlying mechanisms—and potentially, different treatment paths.

What’s Next? HLA Genotyping in Everyday Care
This review strongly supports incorporating HLA genotyping into routine MS care. It could help:

Predict who’s most at risk of MS
Personalize treatment to maximize benefit and minimize harm

Offer clues about how the disease will evolve

Guide prevention strategies—especially for at-risk family members

In short, this research brings us one giant leap closer to truly personalized medicine in MS.

Final Thoughts
The future of MS care isn’t just about new drugs—it’s about using old tools in smarter ways. Your immune system’s genes, especially the HLA complex, are more than background noise—they’re a roadmap. By understanding and using that map, we’re stepping confidently into a new era of precision neurology.

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:
Stamatelos, P., & Anagnostouli, M. (2017). HLA-genotype in multiple sclerosis: the role in disease onset, clinical course, cognitive status and response to treatment: a clear step towards personalized therapeutics. Immunogenet open access, 2(1), 1-12.