Background:The Multiple Sclerosis Severity Score (MSSS) is obtained by normalising the Expanded Disability Status Scale (EDSS) score for disease duration and has been a valuable tool in cross-sectional studies.Objective:To assess whether use of age rather than the inherently ambiguous disease duration was a feasible approach.Method:We pooled disability data from three population-based cohorts and developed an Age Related Multiple Sclerosis Severity (ARMSS) score by ranking EDSS scores based on the patient’s age at the time of assessment. We established the power to detect a difference between groups afforded by the ARMSS score and assessed its relative consistency over time.Results:The study population included 26058 patients from Sweden (n = 11846), Canada (n = 6179) and the United Kingdom (n = 8033). There was a moderate correlation between EDSS and disease duration (r = 0.46, 95% confidence interval (CI): 0.45–0.47) and between EDSS and age (r = 0.44, 95% CI: 0.43–0.45). The ARMSS scores showed comparable power to detect disability differences between groups to the updated and original MSSS.Conclusion:Since age is typically unbiased and readily obtained, and the ARMSS and MSSS were comparable, the ARMSS may provide a more versatile tool and could minimise study biases and loss of statistical power caused by inaccurate or missing onset dates.

In a study based on 96% of the roughly 28,000 patients with multiple sclerosis (MS) in Sweden, Westerlind et al. report relative and absolute MS risks for relatives of patients. Risks were lower than most of those previously reported, with an MS sibling risk seven times that of randomly selected controls.

Objectives We aimed to conduct a systematic review and meta-analysis on the incidence and prevalence of SSc covering the entire literature. Methods This study followed the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement of 2009. We conducted a systematic search in MEDLINE, Web Of Science, and EMBASE to identify articles reporting incidence and/or prevalence of SSc. Two authors conducted the search, reviewed articles for inclusion and extracted relevant data. We used random-effects models to estimate the pooled prevalence and incidence of SSc and performed subgroup analyses by sex, case definition, and region to investigate heterogeneity. We explored the association between calendar period and reported estimates using meta-regression. Results Among 6983 unique records identified, we included 61 studies of prevalence and 39 studies of incidence in the systematic review. The overall pooled prevalence of SSc was 17.6 (95% CI 15.1-20.5) per 100000 and the overall pooled incidence rate of SSc was 1.4 (95% CI 1.1-1.9) per 100000 person-years. We observed significant regional variations in reported estimates; studies conducted in North America reported considerably higher estimates than other regions. The pooled incidence and prevalence in women were 5 times higher than in men. More recent studies reported higher estimates than older ones. Conclusion In this comprehensive review of the incidence and prevalence of SSc across the world, there was large heterogeneity among estimates, which should be taken into consideration when interpreting the results.

Multiple sclerosis (MS) is a complex disease of the central nervous system of unknown etiology. The human leukocyte antigen (HLA) locus on chromosome 6 confers a considerable part of the susceptibility to MS, and the most important factor is the class II allele HLA-DRB1*15:01. In addition, we and others have previously established a protective effect of HLA-A*02. Here, we genotyped 1,784 patients and 1,660 healthy controls from Scandinavia for the HLA-A, HLA-B, HLA-C and HLA-DRB1 genes and investigated their effects on MS risk by logistic regression. Several allele groups were found to exert effects independently of DRB1*15 and A*02, in particular DRB1*01 (OR = 0.82, p = 0.034) and B*12 (including B*44/45, OR = 0.76, p = 0.0028), confirming previous reports. Furthermore, we observed interaction between allele groups: DRB1*15 and DRB1*01 (multiplicative: OR = 0.54, p = 0.0041; additive: AP = 0.47, p = 4×10−06), DRB1*15 and C*12 (multiplicative: OR = 0.37, p = 0.00035; additive: AP = 0.58, p = 2.6×10−05), indicating that the effect size of these allele groups varies when taking DRB1*15 into account. Analysis of inferred haplotypes showed that almost all DRB1*15 bearing haplotypes were risk haplotypes, and that all A*02 bearing haplotypes were protective as long as they did not carry DRB1*15. In contrast, we found one class I haplotype, carrying A*02-C*05-B*12, which abolished the risk of DRB1*15. In conclusion, these results confirms a complex role of HLA class I and II genes that goes beyond DRB1*15 and A*02, in particular by including all three classical HLA class I genes as well as functional interactions between DRB1*15 and several alleles of DRB1 and class I genes.

HLA genotype associates with CC, thus implicating HLA-related immune mechanisms in its pathogenesis.