[Pubmed] HLA polymorphism in neuroimmune diseases: linking antigen presentation to neuroinflammatory programs

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Front Immunol. 2026 Aug 18;17:1863697. doi: 10.3389/fimmu.2026.1863697. eCollection 2026.

ABSTRACT

Human leukocyte antigen (HLA) polymorphism shapes antigen presentation and susceptibility to immune-mediated disease. In neuroimmune disorders, a central question is how HLA-dependent antigen visibility becomes disease-specific immunity and tissue injury. In this Review, we integrate genetic, molecular, cellular, and clinical evidence across multiple sclerosis (MS), neuromyelitis optica spectrum disorder, Guillain-Barré syndrome, narcolepsy, autoimmune encephalitis, and myasthenia gravis. The HLA-DR15-MS axis is the most mechanistically resolved example, linking allele-specific peptide display to autoreactive T-cell repertoires and convergent Epstein-Barr virus-related immune pathways. In other disorders, this upstream principle operates through distinct effectors, target tissues, molecular subtypes, and ancestral contexts, while causal peptide-receptor complexes often remain unresolved. We therefore separate association strength from mechanistic resolution and position glial activation and tissue injury mainly as downstream, context-dependent processes. This evidence-bounded synthesis identifies where HLA mechanisms are established, suggestive, or still inferred from association.

PMID:42682948 | PMC:PMC13531444 | DOI:10.3389/fimmu.2026.1863697


Source: https://pubmed.ncbi.nlm.nih.gov/4268294 ... 8&v=2.20.1