Worldwide risk of autoimmune diseases, particularly multiple sclerosis (MS), varies between populations. One key factor is immune variation attributed to genetic variation. The human leukocyte antigen (HLA) system plays a central role in antigen presentation, immune regulation, and host-pathogen interactions. Variation across HLA genes has substantial clinical implications, influencing risk for autoimmune and neurodegenerative diseases. For instance, HLA-DRB1*15:01 remains the strongest and most consistently replicated genetic risk factor for MS, with similar HLA-associated patterns observed in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Since HLA loci evolve under strong selective pressures, population-level HLA diversity reflects distinct histories of pathogen exposure, geography, climate, diet, and demographic isolation. Indigenous groups such as the First Nations, Métis, and Inuit therefore exhibit unique HLA distributions shaped by their ancestral environments. The variation in HLA genes as well as environmental factors have shaped the difference in MS prevalence and severity in these Indigenous populations compared to non-Indigenous groups.
Current evidence on the genetic architecture of MS, the biological mechanisms linking genetic risk to disease susceptibility and the ways in which genetic factors intersect with environmental exposures to shape clinical outcomes are synthesised.
Jing-Ni He, Nicholas B. Blackburn, V. Jokubaitis· Neurological Therapeutics· 0 citations
This evidence-bounded synthesis identifies where HLA mechanisms are established, suggestive, or still inferred from association across multiple sclerosis, neuromyelitis optica spectrum disorder, Guillain–Barré syndrome, narcolepsy, autoimmune encephalitis, and myasthenia gravis.
Shuo Liu, Si-Wen Yang, Jing Hu et al.· Frontiers in Immunology· 0 citations
Multiple sclerosis (MS) is an immune-mediated, inflammatory, and neurodegenerative disease of the central nervous system with a complex, multifactorial etiology. Familial aggregation, along with a higher concordance rate in monozygotic than dizygotic twins, supports a significant, albeit non-Mendelian, genetic contribu...
Katarzyna Kubicka-Bączyk, Joanna Bączyk, Monika Adamczyk-Sowa· Neurologia i Neurochirurgia...· 0 citations
It is proposed that large-scale T cell receptor repertoire analysis provides a complementary route by identifying disease-associated clonotypes as antigenic footprints that can focus immunopeptidomic and functional studies on candidate antigens, turning HLA associations from statistical signals into testable mechanisms...
H. ElAbd, A. Mahdy, A. Franke· Trends in immunology· 0 citations
Human leukocyte antigen (
HLA
) genes regulate immune function and influence disease susceptibility, but their role in healthy aging is unclear. We investigated whether disease-associated
HLA
alleles affect the likelihood of becoming a cognitively healthy centenarian (CHC). Using imputed
HLA
genotypes from 36...
D. A. Sirvent, N. Tesi, M. Hulsman et al.· npj Aging· 0 citations
Anti-cytokine autoantibodies are increasingly recognized as modulators of immune function and determinants of disease risk, yet their genetic basis and population-level impact remain unclear. Here we perform genome-wide association studies of autoantibodies against IL-1α, IL-6, IL-10, IFN-α, IFN-β, IFN-γ and GM-CSF in...
J. V. von Stemann, Joseph Dowsett, R. Teglgaard et al.· Nature Communications· 0 citations
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