Manuel
Established Member
A new immunology study provides solid evidence that the persistence of Epstein–Barr virus (EBV) is modulated by how HLA class II molecules present viral antigens to CD4⁺ T cells.
https://www.nature.com/articles/s41586-025-10020-2
The study shows that specific differences in antigen presentation may promote:
-prolonged immune stimulation
-viral antigen persistence
-sustained T cell activation
-chronic low-grade inflammation
-loss of immune tolerance
-generation of autoantibodies and autoreactive phenomena
This mechanism is highlighted as relevant for post-viral syndromes, persistent fatigue symptoms, autonomic dysfunction, and chronic inflammatory conditions in which EBV acts as a biological cofactor.
But most importantly, this pathogenic axis is NOT new to us.
We had already described this mechanism in our previous three studies
The processes emphasized in this new work are exactly the same as those proposed in our earlier publications:
EBV as an immunological origin of ME/CFS (Frontiers in Immunology, 2021)
We described that:
-EBV latency and reactivation can generate persistent antigenic stimulation
-this maintains abnormal immune activation
-and promotes loss of immune regulation and chronic systemic symptoms
We proposed that the inability to control EBV-infected cells is a key driver of pathophysiology in patients with HLA-II genetic susceptibility.
https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.656797/full
EBV-induced acquired immunodeficiency in ME/CFS and long COVID
(Journal of Translational Medicine, 2023)
We showed that:
-ME/CFS and long COVID share an EBV reactivation/persistence axis
-leading to a state of chronic immune dysfunction
-with sustained inflammation, impaired antiviral surveillance, and multisystem symptoms, particularly in patients with ancestral HLA-II haplotypes.
https://link.springer.com/article/10.1186/s12967-023-04515-7
Ancestral HLA-II haplotypes and autoimmune diseases
(Frontiers in Immunology, 2025)
Here we linked the genetic component to other autoimmune diseases:
-DR2-DQ6, DR3-DQ2, DR4-DQ8
-haplotypes with broad and potent antigen presentation
-increased risk of persistent immune responses and autoreactivity
-implicated in MS, lupus, RA, T1D, and most autoimmune diseases, including ME/CFS, long COVID, and post-vaccinal syndromes
We proposed that these same haplotypes also shape the immune response to EBV, favoring viral persistence and prolonged inflammation.
https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1710571/full
The new study provides important validation
This new work on EBV confirms—through a different approach—exactly the same model:
Viral persistence + specific HLA-II antigen presentation → chronic immune activation → loss of tolerance → autoimmune phenomena
This is the same pathogenic sequence we had previously proposed for:
-ME/CFS
-long COVID
-post-viral syndromes
-autoimmune diseases
A shared framework: emerging autoimmune diseases driven by antigen persistence
The convergence of evidence supports that:
-ME/CFS
-long COVID
-post-vaccinal syndromes in predisposed individuals
-post-infectious syndromes
share features of emerging autoimmune diseases, in which:
-there is an infectious trigger (often EBV, SARS-CoV-2, or intracellular pathogens with immune evasion mechanisms)
-antigen persistence occurs
-ancestral host HLA-II shapes the immune response
-loss of tolerance and autoreactivity develop
Clinical implication: HLA-II typing as a preventive tool
Taken together, these studies point in a clear direction:
HLA-II haplotype typing should be incorporated into:
-patients with persistent viral infections
-ME/CFS
-long COVID
-post-infectious inflammatory syndromes
-individuals at risk of autoimmunity after infections
Because it allows us to:
-identify susceptibility to viral persistence
-anticipate the risk of chronic immune dysfunction
-stratify patients for early follow-up
-move toward preventive immunogenetic medicine
If you find this information relevant, sharing it or following the page helps it reach those who may need it.
For more information, please read the post on X:
https://www.nature.com/articles/s41586-025-10020-2
The study shows that specific differences in antigen presentation may promote:
-prolonged immune stimulation
-viral antigen persistence
-sustained T cell activation
-chronic low-grade inflammation
-loss of immune tolerance
-generation of autoantibodies and autoreactive phenomena
This mechanism is highlighted as relevant for post-viral syndromes, persistent fatigue symptoms, autonomic dysfunction, and chronic inflammatory conditions in which EBV acts as a biological cofactor.
But most importantly, this pathogenic axis is NOT new to us.
We had already described this mechanism in our previous three studies
The processes emphasized in this new work are exactly the same as those proposed in our earlier publications:
EBV as an immunological origin of ME/CFS (Frontiers in Immunology, 2021)
We described that:
-EBV latency and reactivation can generate persistent antigenic stimulation
-this maintains abnormal immune activation
-and promotes loss of immune regulation and chronic systemic symptoms
We proposed that the inability to control EBV-infected cells is a key driver of pathophysiology in patients with HLA-II genetic susceptibility.
https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.656797/full
EBV-induced acquired immunodeficiency in ME/CFS and long COVID
(Journal of Translational Medicine, 2023)
We showed that:
-ME/CFS and long COVID share an EBV reactivation/persistence axis
-leading to a state of chronic immune dysfunction
-with sustained inflammation, impaired antiviral surveillance, and multisystem symptoms, particularly in patients with ancestral HLA-II haplotypes.
https://link.springer.com/article/10.1186/s12967-023-04515-7
Ancestral HLA-II haplotypes and autoimmune diseases
(Frontiers in Immunology, 2025)
Here we linked the genetic component to other autoimmune diseases:
-DR2-DQ6, DR3-DQ2, DR4-DQ8
-haplotypes with broad and potent antigen presentation
-increased risk of persistent immune responses and autoreactivity
-implicated in MS, lupus, RA, T1D, and most autoimmune diseases, including ME/CFS, long COVID, and post-vaccinal syndromes
We proposed that these same haplotypes also shape the immune response to EBV, favoring viral persistence and prolonged inflammation.
https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1710571/full
The new study provides important validation
This new work on EBV confirms—through a different approach—exactly the same model:
Viral persistence + specific HLA-II antigen presentation → chronic immune activation → loss of tolerance → autoimmune phenomena
This is the same pathogenic sequence we had previously proposed for:
-ME/CFS
-long COVID
-post-viral syndromes
-autoimmune diseases
A shared framework: emerging autoimmune diseases driven by antigen persistence
The convergence of evidence supports that:
-ME/CFS
-long COVID
-post-vaccinal syndromes in predisposed individuals
-post-infectious syndromes
share features of emerging autoimmune diseases, in which:
-there is an infectious trigger (often EBV, SARS-CoV-2, or intracellular pathogens with immune evasion mechanisms)
-antigen persistence occurs
-ancestral host HLA-II shapes the immune response
-loss of tolerance and autoreactivity develop
Clinical implication: HLA-II typing as a preventive tool
Taken together, these studies point in a clear direction:
HLA-II haplotype typing should be incorporated into:
-patients with persistent viral infections
-ME/CFS
-long COVID
-post-infectious inflammatory syndromes
-individuals at risk of autoimmunity after infections
Because it allows us to:
-identify susceptibility to viral persistence
-anticipate the risk of chronic immune dysfunction
-stratify patients for early follow-up
-move toward preventive immunogenetic medicine
If you find this information relevant, sharing it or following the page helps it reach those who may need it.
For more information, please read the post on X:
