Can Your Genes Predict MS Treatment Success? Exploring HLA Markers and Glatiramer Acetate Response
Multiple sclerosis (MS) is a complex autoimmune disease where the immune system attacks the central nervous system. While therapies like Glatiramer Acetate (GA)—an FDA-approved drug mimicking myelin basic protein—help many patients, others see little to no benefit. What if we could predict who would respond, before even starting treatment?
A 2013 study led by Suhayl Dhib-Jalbut and colleagues at UMDNJ-Robert Wood Johnson Medical School aimed to answer this question using genetics. Specifically, the team investigated whether certain HLA class II alleles—the genetic markers that help regulate immune responses—could predict who would benefit from GA therapy in relapsing-remitting MS (RRMS).
The Science Behind It: HLA, GA, and Immune Modulation
The Human Leukocyte Antigen (HLA) system is central to immune recognition. In MS, certain alleles (gene variants), particularly HLA-DRB115:01* (aka DR15) and DQB106:02* (aka DQ6), are strongly linked to increased disease risk. GA works by altering immune cell behavior, shifting the inflammatory response toward a more anti-inflammatory one, especially by targeting these same HLA molecules.
This interplay sparked the hypothesis: could the presence or absence of specific HLA types influence a person’s clinical response to GA?
Study Design: Who Was Studied and How
Subjects: 64 patients with RRMS were enrolled from four MS centers across the U.S.
Treatment: All were treated with GA for at least 2 years.
Outcome Classification:
Responders (GA-R): No relapses and no disability progression (as measured by EDSS).
Non-responders (GA-NR): Had relapses or significant worsening in disability.
Genetic Testing: Blood samples were collected and typed for HLA-DR and HLA-DQ alleles.
Key Findings
1. Certain HLA Alleles Predict Treatment Response
Positive Predictors: Patients carrying DR15 or DQ6 were more likely to respond well.
Negative Predictors: Those carrying DR17 or DQ2 were more likely to show poor response.
2. Haplotypes (Gene Combinations) Matter More Than Single Alleles
Two combinations stood out:
DR15–DQ6: Strongly associated with a favorable response.
DR17–DQ2: Strongly associated with a poor response.
Patients with DR15–DQ6 but without DR17–DQ2 had a 71% chance of being responders. In contrast, those with DR17–DQ2 but lacking DR15–DQ6 had just a 17% chance.
3. A Simple Three-Category Model Emerged:
Good Predicted Response: DR15–DQ6 present, DR17–DQ2 absent
Poor Predicted Response: DR15–DQ6 absent, DR17–DQ2 present
Neutral: Both present or both absent
Why It Matters: Toward Personalized MS Treatment
MS treatment has long been a trial-and-error process. This study is a step toward personalized medicine—using genetic data to tailor therapy choices. HLA typing is already routine in organ transplantation, and incorporating it into MS management could significantly enhance patient outcomes.
Limitations & Next Steps
While promising, the findings must be validated in larger, diverse populations before being adopted into clinical practice. The study’s sample was relatively small (64 patients), and results may differ across ethnic backgrounds.
Additionally, the study looked only at response to GA. Similar analyses across other MS treatments like interferons, natalizumab, or ocrelizumab could further refine therapy choices.
Final Thoughts
The Dhib-Jalbut et al. study offers a hopeful glimpse into a future where MS treatment isn’t one-size-fits-all. If confirmed, a simple HLA test could help patients avoid ineffective therapies and unnecessary side effects, giving them a faster path to control their disease.
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:
Dhib-Jalbut, S., Valenzuela, R. M., Ito, K., Kaufman, M., Picone, M. A., & Buyske, S. (2013). HLA DR and DQ alleles and haplotypes associated with clinical response to glatiramer acetate in multiple sclerosis. Multiple sclerosis and related disorders, 2(4), 340-348.
