The antimicrobial peptide LL37 is a T-cell autoantigen in psoriasis.

Psoriasis is a common T-cell-mediated skin disease with 2-3% prevalence worldwide. Psoriasis is considered to be an autoimmune disease, but the precise nature of the autoantigens triggering T-cell activation remains poorly understood. Here we find that two-thirds of patients with moderate-to-severe plaque psoriasis harbour CD4(+) and/or CD8(+) T cells specific for LL37, an antimicrobial peptide (AMP) overexpressed in psoriatic skin and reported to trigger activation of innate immune cells. LL37-specific T cells produce IFN-γ, and CD4(+) T cells also produce Th17 cytokines. LL37-specific T cells can infiltrate lesional skin and may be tracked in patients blood by tetramers staining. Presence of circulating LL37-specific T cells correlates significantly with disease activity, suggesting a contribution to disease pathogenesis. Thus, we uncover a role of LL37 as a T-cell autoantigen in psoriasis and provide evidence for a role of AMPs in both innate and adaptive immune cell activation.

Volumetric MRI changes, cognition and personality traits in old age depression.

BACKGROUND: The presence of cognitive and structural deficits in euthymic elderly depressed patients remains a matter of debate. Integrative aetiological models assessing concomitantly these parameters as well as markers of psychological vulnerability such as persistent personality traits, are still lacking for this age group. METHODS: Cross-sectional comparisons of 38 elderly remitted patients with early-onset depression (EOD) and 62 healthy controls included detailed neuropsychological assessment, estimates of brain volumes in limbic areas and white matter hyperintensities, as well as evaluation of the Five-Factor personality dimensions. RESULTS: Both cognitive performances and brain volumes were preserved in euthymic EOD patients. No significant group differences were observed in white matter hyperintensity scores between the two groups. In contrast, EOD was associated with significant increase of Neuroticism and decrease of Extraversion facet scores. LIMITATIONS: Results concern the restricted portion of EOD patients without psychiatric and physical comorbidities. Future longitudinal studies are necessary to determine the temporal relationship between the occurrence of depression and personality dimensions. CONCLUSIONS: After remission from acute depressive symptoms, cognitive performances remain intact in elderly patients with EOD. In contrast to previous observations, these patients display neither significant brain volume loss in limbic areas nor increased vascular burden compared to healthy controls. Further clinical investigations on EOD patterns of vulnerability in old age will gain from focusing on psychological features such as personality traits rather than neurocognitive clues.

Outcome of patients with acute coronary syndrome in hospitals of different sizes. A report from the AMIS Plus Registry.

To assess the impact of admission to different hospital types on early and 1-year outcomes in patients with acute coronary syndrome (ACS). Between 1997 and 2009, 31 010 ACS patients from 76 Swiss hospitals were enrolled in the AMIS Plus registry. Large tertiary institutions with continuous (24 hour/7 day) cardiac catheterisation facilities were classified as type A hospitals, and all others as type B. For 1-year outcomes, a subgroup of patients admitted after 2005 were studied. Eleven type A hospitals admitted 15987 (52%) patients and 65 type B hospitals 15023 (48%) patients. Patients admitted into B hospitals were older, more frequently female, diabetic, hypertensive, had more severe comorbidities and more frequent non-ST segment elevation (NSTE)-ACS/unstable angina (UA). STE-ACS patients admitted into B hospitals received more thrombolysis, but less percutaneous coronary intervention (PCI). Crude in-hospital mortality and major adverse cardiac events (MACE) were higher in patients from B hospitals. Crude 1-year mortality of 3747 ACS patients followed up was higher in patients admitted into B hospitals, but no differences were found for MACE. After adjustment for age, risk factors, type of ACS and comorbidities, hospital type was not an independent predictor of in-hospital mortality, in-hospital MACE, 1-year MACE or mortality. Admission indicated a crude outcome in favour of hospitalisation during duty-hours while 1-year outcome could not document a significant effect. ACS patients admitted to smaller regional Swiss hospitals were older, had more severe comorbidities, more NSTE-ACS and received less intensive treatment compared with the patients initially admitted to large tertiary institutions. However, hospital type was not an independent predictor of early and mid-term outcomes in these patients. Furthermore, our data suggest that Swiss hospitals have been functioning as an efficient network for the past 12 years.

Reduced physical activity level and cardiorespiratory fitness in children with chronic diseases.

We aimed to compare physical activity level and cardiorespiratory fitness in children with different chronic diseases, such as type 1 diabetes mellitus (T1DM), obesity (OB) and juvenile idiopathic arthritis (JIA), with healthy controls (HC). We performed a cross-sectional study including 209 children: OB: n = 45, T1DM: n = 48, JIA: n = 31, and HC: n = 85. Physical activity level was assessed by accelerometer and cardiorespiratory fitness by a treadmill test. ANOVA, linear regressions and Pearson correlations were used. Children with chronic diseases had reduced total daily physical activity counts (T1DM 497 +/- 54 cpm, p = 0.003; JIA 518 +/- 28, p < 0.001, OB 590 +/- 25, p = 0.003) and cardiorespiratory fitness (JIA 39.3 +/- 1.7, p = 0.001, OB 41.7 +/- 1.2, p = 0.020) compared to HC (668 +/- 35 cpm; 45.3 +/- 0.9 ml kg(-1) min(-1), respectively). Only 60.4% of HC, 51.6% of OB, 38.1% of JIA and 38.5% of T1DM children met the recommended daily 60 min of moderate-to-vigorous physical activity. Low cardiorespiratory fitness was associated with female gender and low daily PA. Children with chronic diseases had reduced physical activity and cardiorespiratory fitness. As the benefits of PA on health have been well demonstrated during growth, it should be encouraged in those children to prevent a reduction of cardiorespiratory fitness and the development of comorbidities.

The caspase-3-p120-RasGAP module generates a NF-κB repressor in response to cellular stress.

The nuclear factor κB (NF-κB) transcription factor is a master regulator of inflammation. Short-term NF-κB activation is generally beneficial. However, sustained NF-κB might be detrimental, directly causing apoptosis of cells or leading to a persistent damaging inflammatory response. NF-κB activity in stressed cells needs therefore to be controlled for homeostasis maintenance. In mildly stressed cells, caspase-3 cleaves p120 RasGAP, also known as RASA1, into an N-terminal fragment, which we call fragment N. We show here that this fragment is a potent NF-κB inhibitor. Fragment N decreases the transcriptional activity of NF-κB by promoting its export from the nucleus. Cells unable to generate fragment N displayed increased NF-κB activation upon stress. Knock-in mice expressing an uncleavable p120 RasGAP mutant showed exaggerated NF-κB activation when their epidermis was treated with anthralin, a drug used for the treatment of psoriasis. Our study provides biochemical and genetic evidence of the importance of the caspase-3-p120-RasGAP stress-sensing module in the control of stress-induced NF-κB activation.