SynthesisBMC neurology2026
The HLA paradox across populations in multiple sclerosis progression: a systematic review.
Synthesis in BMC neurology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Authors and funding
5 authors.
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Abstract
backgroundMultiple sclerosis (MS) exhibits heterogeneity in disease courses. Although HLA DRB1*15:01 represents the strongest genetic risk factor for MS susceptibility, conferring approximately threefold increased risk, whether this allele similarly influences disease progression remains contentious.
methodsThis systematic review was conducted to clarify the relationship between HLA polymorphisms and the course of multiple sclerosis from inception through November 2025. A three-level random effects meta-analysis was used to account for statistical non-independence. Study quality was evaluated using Q GENIE criteria.
resultsIn total, 56 eligible studies were selected, comprising 22,145 participants; 35 studies contributed 276 effect sizes to quantitative synthesis. The pooled estimate indicated a modest overall association between HLA variants and MS progression (Odds Ratio (OR) 1.30, 95% CI 1.09 to 1.55, p = 0.003). HLA DRB1*15 showed no significant association with disease progression (OR 1.10, 95% CI 0.79 to 1.51, p = 0.57). Exploratory subgroup analysis revealed significant regional heterogeneity (QM = 10.48, p = 0.033): Asian (OR 1.70, p < 0.001) and North American (OR 1.95, p < 0.001) studies suggested significant effects, whereas European studies showed no effect (OR 1.02, p = 0.92). Three alleles demonstrated significant adverse associations: HLA DRB1*04 (OR 1.79, 95% CI 1.33 to 2.42), HLA DRB1*09 (OR 4.21, 95% CI 1.93 to 9.18), and HLA DRB1*03 (OR 1.44, 95% CI 1.01 to 2.05).
conclusionThis systematic review suggests that multiple sclerosis susceptibility and progression appear governed by distinct genetic architectures.
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