Unlocking the Genetic Code of Multiple Sclerosis Treatment: How HLA Genes Influence Interferon Response

Multiple sclerosis (MS), a complex immune-mediated neurodegenerative disease, often strikes in the prime of life, impairing mobility, cognition, and quality of life. For patients with relapsing-remitting MS (RRMS)—the most common form—interferon beta (IFN-β) therapy has long served as a first-line treatment. However, not all patients respond equally. A study takes us one step closer to understanding why—by spotlighting the role of genetics, particularly HLA (human leukocyte antigen) genes, in determining treatment success.

Why Genetics Matter in MS Treatment
The HLA system is a vital part of our immune defense. It helps the body distinguish self from non-self by presenting antigens to T-cells. Variations in these genes can influence susceptibility to autoimmune diseases like MS. But can they also predict how well someone will respond to a specific drug?

That’s the question researchers led by Dr. Ghasem Solgi at Hamadan University of Medical Sciences sought to answer. Their study, published in Pharmacogenomics, analyzed the relationship between HLA class I and II alleles and the effectiveness of IFN-β-1a therapy in 231 RRMS patients.

Study Design: Who Responds & Who Doesn’t?
Patients were treated with IFN-β-1a (brand: CinnoVex) over a two-year period. Based on their clinical outcomes—primarily their Expanded Disability Status Scale (EDSS) scores and relapse rates—they were divided into two groups:

Responders (n=146): No relapses or sustained disability progression.

Nonresponders (n=85): At least one relapse and worsening disability.

A group of 180 healthy individuals served as controls to compare the frequency of specific HLA alleles and haplotypes.

Key Genetic Findings
The results were striking:
HLA-DRB1*04: This allele was significantly more frequent in responders. Patients carrying DRB1*04 were nearly twice as likely to respond well to IFN-β therapy.

HLA-A03 - B44 - DRB1*04 haplotype: This combination of alleles also showed a trend toward better treatment response.

HLA-B*15: On the flip side, patients with this allele were significantly more likely to be nonresponders.

What does this mean in practice? It suggests that certain HLA genotypes may predict whether a patient will benefit from IFN-β therapy—offering a potential roadmap for personalized treatment.

Genetics & MS Risk: Not Just About Response
The study also confirmed previous associations between HLA alleles and MS susceptibility:

Risk alleles: HLA-A03 and DRB115 were associated with higher risk of MS.

Protective alleles: HLA-A02 and DRB114 appeared to offer some protection against the disease.

Interestingly, HLA-B*27, commonly linked with other autoimmune diseases like ankylosing spondylitis, was identified as a risk allele for MS in this population—a novel finding that deserves further exploration.

Limitations & Future Directions
While the findings are promising, they come with caveats:

No screening for neutralizing antibodies: Some nonresponders might have developed antibodies that block IFN-β activity, a known issue with this treatment.

Low-resolution genotyping: High-resolution HLA typing and inclusion of additional loci like HLA-C and DQ could provide a clearer picture.

Ethnic specificity: These results are specific to an cohort and may not apply globally.

Still, the study adds valuable insights to the growing field of MS pharmacogenomics—the science of tailoring drugs based on genetic makeup.

Clinical Implications: Toward Precision Medicine in MS
Imagine a future where, before starting IFN-β therapy, a simple genetic test helps determine whether you’re likely to benefit. If you carry a marker like HLA-DRB104, treatment might proceed with confidence. If you have HLA-B15, your doctor might consider other options from the start, sparing you time, money, and side effects from an ineffective drug.

That’s the promise of personalized medicine—and this study brings us a step closer.

Takeaway: HLA genes, long known to influence MS risk, may also play a critical role in how patients respond to IFN-β therapy. Genetic screening could become a valuable tool in optimizing treatment plans for RRMS.

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:
Mazdeh M, Taheri M, Sayad A, et al. HLA genes as modifiers of response to IFN-β-1a therapy in relapsing-remitting multiple sclerosis. Pharmacogenomics. 2016. DOI: 10.2217/pgs.16.2