Human Leukocyte Antigen alleles associated with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).
Lande, Asgeir, Fluge, Øystein, Strand, Elin B et al. · Scientific reports · 2020 · DOI
Quick Summary
Researchers studied immune system markers called HLA alleles in 426 Norwegian ME/CFS patients and compared them to healthy controls. They found that two specific immune markers (HLA-C*07:04 and HLA-DQB1*03:03) were more common in ME/CFS patients than in healthy people, suggesting the immune system may play a role in developing ME/CFS. About 1 in 5 ME/CFS patients carried one or both of these markers, compared to 1 in 8 healthy people.
Why It Matters
These findings provide the first strong evidence that HLA alleles are associated with ME/CFS susceptibility, supporting the hypothesis that immune dysregulation contributes to disease pathogenesis. This opens avenues for understanding ME/CFS heterogeneity and may eventually inform patient stratification, genetic screening, or immunologically-targeted interventions.
Observed Findings
HLA-C*07:04 allele was present in 7.7% of ME/CFS patients vs. lower prevalence in controls (OR 2.1)
HLA-DQB1*03:03 allele was present in 12.7% of ME/CFS patients vs. lower prevalence in controls (OR 1.5)
Carriage of one or both of these alleles occurred in 19.2% of patients versus 12.2% of controls
The combined allele association was statistically significant (p<0.00003)
All study participants met the Canadian Consensus Criteria for ME/CFS diagnosis
Inferred Conclusions
ME/CFS has an immune genetic component, with HLA alleles contributing to disease susceptibility
ME/CFS is a heterogeneous condition, with these HLA associations likely representing distinct disease subtypes
Autoimmunity may be one underlying mechanism in a subset of ME/CFS patients
Remaining Questions
Do these HLA alleles increase risk through specific pathogenic mechanisms (e.g., molecular mimicry, autoreactive T-cell presentation)?
How do these HLA associations vary across different populations and ancestries?
Are there other genetic and environmental factors that must co-occur with these HLA alleles to trigger ME/CFS?
What This Study Does Not Prove
This study does not prove that these HLA alleles cause ME/CFS—correlation does not equal causation. The genetic associations do not explain why most people with these alleles do not develop ME/CFS, nor do they identify the specific immune mechanisms involved. Results are limited to Norwegian populations and may not apply to other ancestries.