Why do so many people with ME/CFS share the same immune gene variants?
That’s the question driving Manuel Ruiz-Pablos’s research. After becoming severely ill in 2012, he began studying how chronic viral infections like Epstein-Barr might interact with genetic predispositions – particularly HLA-II haplotypes – to drive inflammation, immune exhaustion, and possibly autoimmunity.
“These genes were an advantage in the past,” he explains. “But today, they may leave us vulnerable to long-term immune overactivation – and possibly autoimmunity.”
He is a final-year Biology student at the Universidad Complutense de Madrid; and an external collaborator with the team of Bruno Paiva, PhD, and Aintzane Zabaleta, PhD, CIMA, University of Navarra, focusing on ME/CFS, Long COVID, and other post-viral conditions. He was a member Paiva’s team that was awarded a Solve Ramsay Research Grant for their study, “Possible class II MHC deficiency in patients with ME/CFS.“
In this interview with Solve Director of Advocacy Monique Wike, Ruiz-Pablos shares:
- How a personal health crisis launched his research
- Why he focuses on HLA-II genetics and herpesviruses
- What gives him hope as both a patient and a scientist
- What he’d say to policymakers, and to other patients
Watch the full interview here. You can also read his most recent publication here.
This interview is in Spanish. To watch the video with English captions, follow these steps:
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Read the full transcript of this interview in English here.
Read an abbreviated version of the questions and answers for this interview in English below:
1. ORIGIN STORY: FROM PATIENT TO RESEARCHER
Monique Wike: What surprised you most in your research?
Manuel Ruiz-Pablos: I became ill in 2012, after an Epstein-Barr infection. At the time, I didn’t know that virus would end up causing my illness. I developed dizziness, autonomic symptoms, and gastrointestinal problems. I had to leave medical school, and I spent nearly eight years mostly housebound. At some point, I had to decide: either stay in bed with no help, or start investigating the disease myself.
MW: How did you arrive at your research hypothesis?
MR-P: By reviewing the literature, I developed the hypothesis that there is a genetic predisposition — particularly in HLA-II alleles — that could make viral infections more severe. These HLA-II variants are well known in autoimmune diseases. Our idea was that chronic viral antigens, like those from herpesviruses, could drive long-term immune activation in people with these genetic profiles.
2. THE HYPOTHESIS: GENETICS + VIRAL TRIGGERS
MW: How did you arrive at your research hypothesis?
MR-P: By reviewing the literature, I developed the hypothesis that there is a genetic predisposition — particularly in HLA-II alleles — that could make viral infections more severe. These HLA-II variants are well known in autoimmune diseases. Our idea was that chronic viral antigens, like those from herpesviruses, could drive long-term immune activation in people with these genetic profiles.
3. THE HAPLOTYPES THEMSELVES
MW: What have you found about HLA-II haplotypes and autoimmune risk?
MR-P: Our project focuses on three HLA-II class II haplotypes: DR2-DQ6, DR3-DQ2, and DR4-DQ8. These haplotypes appear in up to 90% of autoimmune diseases like lupus, multiple sclerosis, rheumatoid arthritis, and type 1 diabetes. What’s striking is that these same haplotypes are also among the most prevalent in European populations.
4. WHY CHRONIC VIRUSES MATTER
MW: Why do chronic infections play such a critical role?
MR-P: Viruses like Epstein-Barr remain in the body and constantly present antigens. In people with these haplotypes, that leads to exaggerated immune responses — higher cytokine production and chronic inflammation. Over time, that chronic inflammation increases susceptibility to autoimmune disease
5. ME/CFS, LONG COVID, AND STIGMA
MW: How did Long COVID change the conversation around ME/CFS?
MR-P: When Long COVID appeared, I saw people describing exactly the same symptoms I had. I tried to tell them, ‘This is ME/CFS,’ but the disease was still socially rejected. People said it was psychosomatic. The same thing happened historically with many autoimmune diseases — until biomarkers were found.
6. POLICY & FUNDING
MW: If you had one minute with a policymaker, what would you say?
MR-P: I would tell them to invest more in research on ME/CFS, Long COVID, and post-viral syndromes. If we don’t, healthcare systems will carry a much larger burden later — patients developing autoimmunity, dysautonomia, neurological disease, even cancer. Investing now is prevention.
7. MESSAGE TO FELLOW PATIENTS
MW: What would you say to a patient struggling to hold onto hope?
MR-P: I’m an example that improvement is possible. I couldn’t study, I couldn’t leave the house, I couldn’t eat normally. Now, with antivirals, antihistamines, and what research has taught me, I can go to university, exercise carefully, and have a social life. If there were no hope, I wouldn’t be here today.
