Summary
Background
A strong link between disease severity and Staphylococcus aureus colonization of the skin has been reported in patients with atopic dermatitis (AD).
Objectives
To examine temporal ...variations in S. aureus colonization and S. aureus CC type in patients with AD, and to investigate links to disease severity, skin barrier properties and filaggrin gene (FLG) mutations.
Methods
This was a follow‐up study of a cohort of 101 adult patients with AD recruited from an outpatient clinic. Bacterial swabs were taken at baseline and follow‐up from lesional skin, nonlesional skin and the nose. Swabs positive for S. aureus were characterized by spa and the respective clonal complex (CC) type was assigned. Patients were characterized with respect to disease severity Scoring Atopic Dermatitis (SCORAD), skin barrier properties transepidermal water loss (TEWL), pH and FLG mutations.
Results
In total, 63 patients participated in a follow‐up visit. Twenty‐seven patients (43%) were colonized at both visits, 27 were colonized at only one visit and nine (14%) were not colonized at either visit. Of patients colonized at both visits, 52% remained colonized with the same CC type at follow‐up. Change in CC type was related to an increase in SCORAD of 10·7 points; patients who carried the same CC type had a reduction in SCORAD of 4·4 points. Significantly higher skin pH was found in patients colonized at both visits, while change in CC type was not related to TEWL, pH or FLG mutations.
Conclusions
The data indicate that temporal variation in S. aureus CC type is linked to flares of the disease.
What's already known about this topic?
Patients with atopic dermatitis (AD) have a predisposition to skin infections with Staphylococcus aureus.
Skin barrier impairments in AD associate with S. aureus colonization.
Staphylococcus aureus is strongly linked to disease severity in AD.
What does this study add?
Change in S. aureus CC type is related to increased disease severity.
Staphylococcus aureus CC types undergo temporal variation in less than half of the colonized patients.
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Background:
Previous studies of multiple sclerosis (MS) have indicated differences in the pathogenesis in relapsing–remitting (RRMS), secondary progressive (SPMS) and primary progressive (PPMS) ...disease.
Objective:
We hypothesized that different MS subtypes would show differences in gene expression that could be traced to specific subsets of peripheral blood mononuclear cells (PBMCs).
Methods:
Gene expression in RRMS, SPMS, PPMS and healthy control (HC) PBMCs was analyzed on Affymetrix arrays. In addition, we studied gene expression in pools of purified PBMC subsets.
Results:
We found 380 genes that were differentially expressed in RRMS, PPMS, SPMS and HCs (false discovery rate < 5%). There were no major differences between the subtypes of MS. The genes showing most prominent expression changes in RRMS were associated with adaptive immune pathways, while genes in PPMS were associated with innate immune system pathways. SPMS patients shared pathways with RRMS and PPMS patients. Gene expression changes were most prominent in B cells, CD8+ T cells and monocytes.
Conclusion:
Differences in gene expression, which could be traced to B cells, CD8+ T cells and monocytes, were found between MS patients and HCs but only minor differences were observed between MS subgroups.
Background and purpose
The social and economic consequences of comorbidity in multiple sclerosis (MS) are largely unexplored. Differences were investigated in income and in the rate of broken ...relationships between cases of MS with and without chronic comorbidity.
Methods
We conducted a nationwide cohort study including all incident cases of MS in Denmark with clinical MS onset between 1980 and 2005. The difference in income was investigated at MS onset and 5 and 10 years after MS onset. The difference in the rate of broken relationships was investigated in subjects who were in a relationship at MS onset or who entered a relationship after MS onset. We used logistic, multiple linear and Poisson regression analyses.
Results
Cases of MS with somatic comorbidity had increased odds of low incomes both 5 years {odds ratio (OR), 1.41 95% confidence interval (CI), 1.19–1.67; P < 0.0005} and 10 years OR, 1.37 (95% CI, 1.17–1.60); P < 0.0005 after MS onset. The odds of a low income with psychiatric comorbidity was increased 10 years after MS onset OR, 3.06 (95% CI, 1.47–6.37); P = 0.003. The rate of broken relationships was increased in cases of MS with any somatic comorbidity incidence rate ratio, 1.46 (95% CI, 1.32–1.61); P < 0.0005.
Conclusions
Our results underscore the burden of comorbidity in MS on patients, their partners and society.
Summary
Expression of the forkhead box protein 3 (FoxP3) transcription factor is regulated by the E3 ubiquitin ligases Itch and Cbl‐b and induces regulatory activity CD4+CD25high T cells. Treatment ...with interferon (IFN)‐β enhances regulatory T cell activity in multiple sclerosis (MS). We studied the phenotype of CD4+CD25high T cells in MS by flow cytometry and its relationship with expression of the FOXP3, ITCH and CBLB genes. We found that untreated MS patients had lower cell surface expression of cytotoxic T lymphocyte antigen 4 (CTLA‐4) on CD4+CD25high T cells and higher intracellular CTLA‐4 expression than healthy controls. Cell surface expression of CTLA‐4 on CD4+CD25high T cells correlated with expression of FOXP3 mRNA in untreated patients and increased significantly with time from most recent injection in patients treated with IFN‐β. FOXP3 mRNA expression correlated with CBLB and ITCH and T helper type 2 cytokine mRNA expression in MS patients. These data link expression of FOXP3, CBLB and ITCH mRNA and CTLA‐4 expression on the surface of CD4+CD25high T cell in MS. We hypothesize that this may reflect alterations in the inhibitory effect of CTLA‐4 or in regulatory T cell function.
Background: Low IGF-I levels may be associated with the development of stroke; however, prospective data appear to be unavailable.
Methods: This was a nested case-control study within a Danish ...follow-up study, including 57,053 men and women. Baseline data included circulating IGF-I, IGF-II, and IGF binding protein (IGFBP)-3 concentrations as well as lifestyle factors and medical history. We identified 254 cases with incident ischemic stroke and 254 gender- and age-matched controls.
Results: Participants in the bottom quartiles of IGF-I and IGFBP-3 levels (median concentrations, 72 and 2937 ng/ml, respectively) were at increased risk of ischemic stroke, e.g. adjusted odds ratios (ORs) of 2.06 95% confidence interval (CI), 1.05–4.03 and 2.29 (95% CI, 1.17–4.49), respectively, when compared with participants in the top quartiles (median concentrations, 125 and 4835 ng/ml, respectively). A negative, although weaker, association was also found for IGF-II (adjusted OR 1.44, 95% CI 0.79–2.64) when comparing the bottom quartile with the top quartile. No substantial associations were seen for IGF-I and IGF-II when also adjusting for IGFBP-3; adjusting IGFBP-3 for IGF-I and -II had only a minor impact on the risk estimates.
Conclusion: These findings give some support to the hypothesis that the IGF axis is involved in the pathogenesis of ischemic stroke.
Multiple sclerosis (MS) is an immune‐mediated disease where T cells are thought to initiate an inflammatory reaction in the brain and spinal cord, resulting in demyelination and axonal pathology. ...Interfering with the activation and recruitment of immune cells reduces disease activity in MS. We review the mechanism of action and treatment effects of natalizumab and fingolimod, which interfere with the recruitment of pathogenic immune cells in MS. Fingolimod blocks the egress of activated lymphocytes from lymph nodes by binding to the sphingosine‐1‐phosphate (S1P) receptor 1, but may also have effects on S1P receptor‐expressing cells within the central nervous system (CNS). Natalizumab reduces the migration of lymphocytes to the CNS by binding to the α4 integrin very late antigen 4. Fingolimod and natalizumab also have other effects, but these are less well understood. Both treatments are efficacious in reducing relapses, accumulation of persisting disability and magnetic resonance imaging disease activity. Both treatments are safe and well tolerated in the majority of patients, but due to a potential for serious side effects they are licensed as second line therapies or for treatment of highly active MS in most European countries. We conclude that fingolimod and natalizumab have well known effects on the migration of immune cells in MS and have substantial effects on disease activity in relapsing−remitting MS. Additional effects on disease progression, potential effects within the CNS and other effects on immune cells are still being clarified.
Background: Atherosclerotic disease has been associated with the risk of venous thromboembolism, but the available data are conflicting. There are similar confusions regarding the association of the ...use of aspirin and statins with venous thromboembolism. Objectives: To determine whether arterial cardiovascular events, use of statins and low‐dose aspirin were associated with the risk of venous thromboembolism. Patients and methods: In this population‐based case–control study, we identified 5824 patients with venous thromboembolism and 58 240 population controls with a complete hospital and prescription history. We used logistic regression to estimate the relative risk of venous thromboembolism, adjusted for potentially confounding factors. Results: Patients with a history of arterial cardiovascular events had a clearly increased relative risk. An event within 3 months before the index date conferred large increases in risk relative risk 4.22 (95% confidence interval (CI), 2.33–7.64) after myocardial infarction, 4.41 (95% CI, 2.92–6.65) after stroke. Myocardial infarction more than 3 months before the index date was not significantly associated with risk, although there was a relative risk of 1.29 (95% CI, 1.05–1.57) for myocardial infarction more than 60 months previously. A history of stroke was associated with small increases in risk after 3 months. Current use of statins was associated with a reduced risk of venous thromboembolism relative risk = 0.74 (95% CI, 0.63–0.85). Aspirin use was not associated with risk. Conclusions: Patients with cardiovascular events are at a short‐term increased risk of venous thromboembolism. Statins might prevent venous thromboembolism but aspirin does not. However, as the study is non‐randomized residual confounding cannot be excluded.
Objective
The primary objective of this study was to develop a quantitative test to assess ambulation in multiple sclerosis (MS) patients that is more accurate and sensitive than the Timed 25-foot ...walk (T25FW). For this purpose, we developed the Six Spot Step Test (SSST), which besides speed includes co-ordination and balance, to be a lower limb counterpart to the 9-Hole Peg Test (9HPT).
Background
The T25FW, which is the ambulation test of the MS Functional Composite (MSFC), reflects only the speed component of walking. The lack of sensitivity to other components of gait adds to the floor effect.
Methods and patients
In the SSST, the patient is instructed to walk as quickly as possible from one end to the other of a rectangular field measuring 1× 5 m, while kicking five cylinder blocks out of five circles marked on the floor. Some 151 MS patients with the Expanded Disability Status Scale (EDSS) score 0-6.5 and 64 normal controls performed the SSST and the T25FW. In addition, 41 patients performed the tests twice.
Results
The range of the SSST (4.7-35.1 seconds) was wider than that of the T25FW (3.5-22.6 seconds). Using control mean+ 2 SD as cut off, 107 patients had abnormal SSST, while 100 patients had abnormal T25FW. The T25FW (mean) increased 2.1 seconds over the EDSS range of 0-4.0, while the SSST increased 4.9 seconds. The intra-class correlation between repeated tests (r) was 0.95 for the SSST and 0.96 for the T25FW. The correlation between the SSST and the T25FW was high (r=0.92).
Conclusion
The SSST seems to be superior to the T25FW in terms of dynamic range, floor effect and discriminatory power. The SSST is a relevant alternative for the T25FW as the ambulation component of the MSFC.
Background:
Treatment with glatiramer acetate (GA) modestly decreases disease activity in multiple sclerosis (MS). The mechanism of action is incompletely understood and differences in the response ...to treatment between individuals may exist.
Objective:
To study the activation of CD4+ T cells, monocytes and dendritic cells (DC) in relation to disease activity in MS patients treated with GA.
Methods:
Flow cytometry was used to study the activation of CD4+ T cells and T cell subsets (CD25high and CD26high cells), monocytes and DCs in a cross-sectional study of 39 untreated and 29 GA-treated MS patients, the latter followed prospectively for one year. Gd-enhanced magnetic resonance imaging (MRI) studies were conducted in all patients. Disease activity was assessed as relapses.
Results:
The median percentage of DCs expressing CD40 was 10% in untreated MS patients and 5.9% in GA-treated patients (Bonferroni-corrected p=0.0005). The hazard ratio of relapse was 1.32 (95% confidence interval 1.05–1.64) per 1% increase in CD40+ DCs. Patients treated with GA had fewer CD4+ T cells expressing surface markers associated with T helper type 1 effector responses and more CD4+ T cells expressing surface markers associated with regulatory, naïve or central memory T cell populations, but CD4+ T cell activation was not related with relapse risk.
Conclusions:
MS patients treated with GA show prominent changes in circulating antigen-presenting cells and CD4+ T cells. Expression of CD40 on DCs is significantly lower and associated with relapse risk in MS patients treated with GA.
The objectives were to study the expression of very late antigen (VLA)-4, melanoma cell adhesion molecule-1 (MCAM-1) and activated leukocyte cell adhesion molecule (ALCAM) on CD4+ T cells during ...natalizumab treatment and to investigate the association with disease activity.
We find that subgroups of autoreactive T cells are retained in peripheral blood, in particular MOG-reactive CD4+ T cells expressing MCAM-1. The expression of MCAM-1 or ALCAM on CD4+ T cells was, however, not clearly associated with disease activity (clinical or MRI) during natalizumab treatment. We confirm upregulation of MCAM-1 on CD4+ T cells during natalizumab treatment while VLA-4 is downregulated.
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•Natalizumab treated patients had a lower percentage of CD4+ T cells in CSF expressing VLA-4.•Natalizumab treated patients had a higher percentage of CD4+ T cells expressing MCAM-1 in CSF.•Natalizumab treated patients had a higher percentage of MOG-reactive CD4+ T cells in blood.•Stable natalizumab patients had a higher increase of MOG-reactive CD4+ T cells expressing MCAM-1 in blood.•No association between disease activity and expression of MCAM-1 or ALCAM in blood of natalizumab-treated patients
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