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Objective The risk of multiple sclerosis (MS) is influenced by HLA-DRB1, while protective effects have been proposed for HLA-A*02 and HLA-C*05 . Our aim was to further understand the role of HLA class I in MS through a comprehensive investigation. Methods 1529 MS patients and 1814 controls from Sweden and Norway were genotyped for HLA-DRB1 , HLA-A , and HLA-C . Simultaneous analysis of all alleles while adjusting for confounding was achieved using logistic regression. Results We observed independent effects of all three genes. We confirm the HLA-A*02 (OR = 0.73, p = 9.2 × 10 − 4 ) association and report a novel effect of HLA-C*08 (OR = 1.85, p = 0.0093). Conclusions The HLA class I region contains two factors modulating MS risk, characterized by independent associations with HLA-A and HLA-C.

Axonal damage, a core feature of neurological diseases, induces a retrograde reaction in neurons and surrounding glia. We determined transcriptional profiles of this reaction using Affymetrix oligonucleotide arrays. Gene expression was examined in spinal cord tissue prior to injury and following ventral root avulsion in two inbred rat strains, where the degree of neurodegeneration differs. Stringent statistical analysis revealed 278 regulated genes, whereof 245 were regulated by the injury and 68 differed between strains. Principal component analysis disclosed a common injury response pattern significantly modified by genetic background. Notably, inflammatory genes comprised the largest group of genes induced by injury and these transcripts prevailed in the strain most susceptible to neurodegeneration. In addition, levels of the strain regulated genes C1qb and Timp1 correlated with degree of neurodegeneration in a cohort of genetically heterogeneous animals. These results suggest a link between the inflammatory response elicited by nerve injury and subsequent neurodegeneration.

B cells play an indispensable, yet indeterminate, role in the pathogenesis of multiple sclerosis (MS). We measured mRNA of APRIL–a promotor of B-cell survival–in peripheral blood and quantified protein levels in plasma and cerebrospinal fluid in MS patients and controls. APRIL mRNA levels in monocytes and T cells were significantly higher in MS patients than in controls. Levels of soluble APRIL in plasma were higher in patients with chronic progressive MS than in patients with relapsing–remitting MS, albeit not significantly. MS may thus be associated with increased transcription in peripheral blood of factors promoting B-cell survival, including APRIL.