Immunomodulatory disease-modifying therapies target lymphocytes, and particularly B cells, to prevent clinical and radiological inflammatory activity.3 However, despite the availability of these ...therapies, insidious neurological disability continues to accumulate in some patients.4 Clinical outcomes can be highly heterogeneous not only among unrelated individuals, but also between family members.5 Until recently, the large cohorts with long-term data necessary to accurately define individual trajectories have not been available, hindering the identification of genetic drivers of outcome. The International Multiple Sclerosis Genetics Consortium and the MultipleMS Consortium have now reported what is, to our knowledge, the first study to identify and replicate a genetic signal associated with disease severity.6 In a discovery cohort of more than 12 500 White Europeans with multiple sclerosis, the consortia identified a single variant, present in approximately 17% of study participants, associated with increased risk of disease progression (effect size 0·089, p=9·7 × 10−9). Neither study found variants with moderate or large effect sizes, and both found that outcomes are not highly heritable, with heritability estimates of 13%6 and 20%,1 consistent with findings from previous work.7 Where do these studies now leave our understanding of multiple sclerosis outcomes?
The impact of menopause on multiple sclerosis Bridge, Francesca; Butzkueven, Helmut; Van der Walt, Anneke ...
Autoimmunity reviews,
August 2023, 2023-08-00, Letnik:
22, Številka:
8
Journal Article
Recenzirano
Menopause, defined as the permanent cessation of ovarian function, represents a period of significant fluctuation in sex hormone concentrations. Sex hormones including oestrogen, progesterone, ...testosterone and anti-Mullerian hormone are thought have neuroinflammatory effects and are implicated in both neuroprotection and neurodegeneration. Sex hormones have a role in modifying clinical trajectory in multiple sclerosis (MS) throughout the lifespan. MS predominantly effects women and is typically diagnosed early in a woman's reproductive life. Most women with MS will undergo menopause. Despite this, the effect of menopause on MS disease course remains unclear. This review examines the relationship between sex hormones and MS disease activity and clinical course, particularly around the time of menopause. It will consider the role of interventions such as exogenous hormone replacement therapy in modulating clinical outcomes in this period. Understanding the impact of menopause on multiple sclerosis is fundamental for delivering optimal care to women with MS as they age and will inform treatment decisions with the aim of minimising relapses, disease accrual and improving quality of life.
•Menopause is associated with changes in sex hormones and the immunological profile which may impact MS disease course.•Conflicting evidence on the impact of menopause on MS remain an important gap in the literature.•Understanding the impact of menopause is critical for reducing disability and improving quality of life for women with MS.
Concerns regarding infection with the novel coronavirus SARS-CoV-2 leading to COVID-19 are particularly marked for pregnant women with autoimmune diseases such as multiple sclerosis (MS). There is ...currently a relative paucity of information to guide advice given to and the clinical management of these individuals. Much of the limited available data around COVID-19 and pregnancy derives from the obstetric literature, and as such, neurologists may not be familiar with the general principles underlying current advice. In this article, we discuss the impact of potential infection on the pregnant woman, the impact on her baby, the impact of the current pandemic on antenatal care, and the interaction between COVID-19, MS and pregnancy. This review provides a framework for neurologists to use to guide the individualised advice given to both pregnant women with MS, and those women with MS who are considering pregnancy. This includes evidence derived from previous novel coronavirus infections, and emerging evidence from the current pandemic.
•The historic assumption that MS relapse rate reduces during pregnancy and increases again post-partum remains true, despite significant changes in the MS treatment landscape, and increasing rates of ...treatment with DMT.•MS relapse rate appears to be decreasing over time in women both prior to pregnancy and in the post-partum period.•Neither diagnostic criteria, DMT exposure, nor proportion of women breastfeeding appears to associate with the change in relapse rate at a population level.
Women with MS are advised that relapse rates fall during pregnancy and rebound post-partum. This advice originates from 1998; smaller, more recent, studies have not been previously pooled.
All studies published since 1998 providing raw relapse data were considered for inclusion. Single arm meta-analysis was performed using a restricted maximum likelihood random effects model with inverse variance; secondary subgroup analysis and meta regression were then performed. Annualised relapse rates (ARR), or relapse numbers/rates suitable for conversion into ARR during pregnancy and the post-partum period were included. Secondary subgroup analysis examined year of data collection, DMT exposure, breastfeeding and data source.
7034 pregnancies from 6430 women were included. ARR fell from 0.57 (95%CI 0.45-0.70) pre-pregnancy to 0.36 (0.28-0.44), 0.29 (0.21-0.36) and 0.16 (0.11-0.21) during trimesters 1,2, and 3, with a post-partum rebound (ARR 0.85, 95%CI 0.70-1.00). ARR reduced pre-pregnancy and post-partum over time (p<0.001). Relapse rates were lower in claims databases than elsewhere.
Despite high heterogeneity, we confirm the historic assumption that ARR reduces during pregnancy, and demonstrate an overall reduction in ARR over time. Studies using data originating from claims databases demonstrated a lower relapse rate at all time points, which has not previously been demonstrated.
Background Autoimmune conditions (AICs) and/or their treatment may alter risk of human papilloma virus (HPV) infection and females with AICs are therefore at an increased risk of cervical dysplasia. ...However, inclusion of these at-risk populations in cervical cancer screening and HPV-vaccination guidelines, are mostly lacking. This study aimed to determine the prevalence of cervical dysplasia in a wide range of AICs and compare that to HIV and immunocompetent controls to support the optimisation of cervical cancer preventive health measures. Methods Data linkage was used to match cervical screening episodes to emergency department records of females with AICs or HIV to immunocompetent controls over a 14-year period. The primary outcome was histologically confirmed high-grade cervical disease. Results, measured as rates by cytology and histology classification per 1,000 females screened, were analysed per disease group, and intergroup comparisons were performed. Results Females with inflammatory bowel disease (2,683), psoriatic and enteropathic arthropathies (1,848), multiple sclerosis (MS) (1,426), rheumatoid arthritis (1,246), systemic lupus erythematosus and/or mixed connective tissue disease (SLE/MCTD) (702), HIV (44), and 985,383 immunocompetent controls were included. SLE/MCTD and HIV groups had greater rates of high-grade histological and cytological abnormalities compared to controls. Increased rates of low-grade cytological abnormalities were detected in all females with AICs, with the exception of the MS group. Conclusions Females with SLE/MCTD or HIV have increased rates of high-grade cervical abnormalities. The increased low-grade dysplasia rate seen in most females with AICs is consistent with increased HPV infection. These findings support expansion of cervical cancer preventative programs to include these at-risk females.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The aetiology and pathophysiology of complex diseases are driven by the interaction between genetic and environmental factors. The variability in risk and outcomes in these diseases are incompletely ...explained by genetics or environmental risk factors individually. Therefore, researchers are now exploring the epigenome, a biological interface at which genetics and the environment can interact. There is a growing body of evidence supporting the role of epigenetic mechanisms in complex disease pathophysiology. Epigenome-wide association studies (EWASes) investigate the association between a phenotype and epigenetic variants, most commonly DNA methylation. The decreasing cost of measuring epigenome-wide methylation and the increasing accessibility of bioinformatic pipelines have contributed to the rise in EWASes published in recent years. Here, we review the current literature on these EWASes and provide further recommendations and strategies for successfully conducting them. We have constrained our review to studies using methylation data as this is the most studied epigenetic mechanism; microarray-based data as whole-genome bisulphite sequencing remains prohibitively expensive for most laboratories; and blood-based studies due to the non-invasiveness of peripheral blood collection and availability of archived DNA, as well as the accessibility of publicly available blood-cell-based methylation data. Further, we address multiple novel areas of EWAS analysis that have not been covered in previous reviews: (1) longitudinal study designs, (2) the chip analysis methylation pipeline (ChAMP), (3) differentially methylated region (DMR) identification paradigms, (4) methylation quantitative trait loci (methQTL) analysis, (5) methylation age analysis and (6) identifying cell-specific differential methylation from mixed cell data using statistical deconvolution.
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