T Helper 1 Cellular Immunity Toward Recoverin Is Enhanced in Patients With Active Autoimmune Retinopathy

Autoimmune retinopathy (AIR) causes rapidly progressive vision loss that is treatable but often is confused with other forms of retinal degeneration including retinitis pigmentosa (RP). Measurement of anti-retinal antibodies (ARA) by Western blot is a commonly used laboratory assay that supports the diagnosis yet does not reflect current disease activity. To search for better diagnostic indicators, this study was designed to compare immune biomarkers and responses toward the retinal protein, recoverin, between newly diagnosed AIR patients, slow progressing RP patients and healthy controls. All individuals had measurable anti-recoverin IgG and IgM antibodies by ELISA regardless of disease status or Western blot results. Many AIR patients had elevated anti-recoverin IgG1 levels and a strong cellular response toward recoverin dominated by IFNγ. RP patients and controls responded to recoverin with a lower IFNγ response that was balanced by IL-10 production. Both AIR and RP patients displayed lower levels of total peripheral blood mononuclear cells that were due to reductions of CD4+ TH cells. A comparison of messenger RNA (mRNA) for immune-related genes in whole blood of AIR patients versus RP patients or controls indicated lower expression of ATG5 and PTPN22 and higher expression of several genes involved in TH cell signaling/transcription and adhesion. These data indicate that an immune response toward recoverin is normal in humans, but that in AIR patients the balance shifts dramatically toward higher IFNγ production and cellular activation

Knowledge co-production for decision-making in human-natural systems under uncertainty

Decision-making under uncertainty is important for managing human-natural systems in a changing world. A major source of uncertainty is linked to the multi-actor settings of decisions with poorly understood values, complex relationships, and conflicting management approaches. Despite general agreement across disciplines on co-producing knowledge for viable and inclusive outcomes in a multi-actor context, there is still limited conceptual clarity and no systematic understanding on what co-production means in decision-making under uncertainty and how it can be approached. Here, we use content analysis and clustering to systematically analyse 50 decision-making cases with multiple time and spatial scales across 26 countries and in 9 different sectors in the last decade to serve two aims. The first is to synthesise the key recurring strategies that underpin high quality decision co-production across many cases of diverse features. The second is to identify important deficits and opportunities to leverage existing strategies towards flourishing co-production in support of decision-making. We find that four general strategies emerge centred around: promoting innovation for robust and equitable decisions; broadening the span of co-production across interacting systems; fostering social learning and inclusive participation; and improving pathways to impact. Additionally, five key areas that should be addressed to improve decision co-production are identified in relation to: participation diversity; collaborative action; power relationships; governance inclusivity; and transformative change. Characterising the emergent strategies and their key areas for improvement can help guide future works towards more pluralistic and integrated science and practice

The Determinants of young Adult Social well-being and Health (DASH) study: diversity, psychosocial determinants and health.

Purpose: The Determinants of young Adult Social well-being and Health longitudinal study draws on life-course models to understand ethnic differences in health. A key hypothesis relates to the role of psychosocial factors in nurturing the health and well-being of ethnic minorities growing up in the UK. We report the effects of culturally patterned exposures in childhood. Methods: In 2002/2003, 6643 11–13 year olds in London, ~80 % ethnic minorities, participated in the baseline survey. In 2005/2006, 4782 were followed-up. In 2012–2014, 665 took part in a pilot follow-up aged 21–23 years, including 42 qualitative interviews. Measures of socioeconomic and psychosocial factors and health were collected. Results: Ethnic minority adolescents reported better mental health than White British, despite more adversity (e.g. economic disadvantage, racism). It is unclear what explains this resilience but findings support a role for cultural factors. Racism was an adverse influence on mental health, while family care and connectedness, religious involvement and ethnic diversity of friendships were protective. While mental health resilience was a feature throughout adolescence, a less positive picture emerged for cardio-respiratory health. Both, mental health and cultural factors played a role. These patterns largely endured in early 20s with family support reducing stressful transitions to adulthood. Education levels, however, signal potential for socio-economic parity across ethnic groups

CD19+CD24hiCD38hi B Cells Are Expanded in Juvenile Dermatomyositis and Exhibit a Pro-Inflammatory Phenotype After Activation Through Toll-Like Receptor 7 and Interferon-α

Juvenile dermatomyositis (JDM) is a rare form of childhood autoimmune myositis that presents with proximal muscle weakness and skin rash. B cells are strongly implicated in the pathogenesis of the disease, but the underlying mechanisms are unknown. Therefore, the main objective of our study was to investigate mechanisms driving B cell lymphocytosis and define pathological features of B cells in JDM patients. Patients were recruited through the UK JDM Cohort and Biomarker study. Peripheral blood B cell subpopulations were immunophenotyped by flow cytometry. The results identified that immature transitional B cells were significantly expanded in active JDM, actively dividing, and correlated positively with disease activity. Protein and RNAseq analysis revealed high interferon alpha (IFNa) and TLR7-pathway signatures pre-treatment. Stimulation of B cells through TLR7/8 promoted both IL-10 and IL-6 production in controls but failed to induce IL-10 in JDM patient cells. Interrogation of the CD40-CD40L pathway (known to induce B cell IL-10 and IL-6) revealed similar expression of IL-10 and IL-6 in B cells cultured with CD40L from both JDM patients and controls. In conclusion, JDM patients with active disease have a significantly expanded immature transitional B cell population which correlated with the type I IFN signature. Activation through TLR7 and IFNa may drive the expansion of immature transitional B cells in JDM and skew the cells toward a pro-inflammatory phenotype

Study of thrombopoietin levels in some Egyptian patients with chronic liver diseases secondary to the hepatitis C virus

IntroductionThe hepatitis C virus (HCV) is a leading cause of chronic liver disease (CLD), cirrhosis, and hepatocellular carcinoma, as well as the most common indication for liver transplantation in many countries. PurposeThis work was carried out to study of thrombopoietin (TPO) level in Egyptian patients with chronic hepatitis C and liver cirrhosis with HCV. Patients and methods This work was conducted on 40 patients proved to have chronic liver disease due to chronic HCV infection by positive HCV antibody by enzyme-linked immunosorbent assay, PCR for HCV RNA, abdominal ultrasonography, and histopathological examination. Twenty of these patients had chronic active hepatitis C (CAH) and the other 20 patietns had liver cirrhosis. Fifteen apparently healthy individuals (negative for HCV antibody) were included in a control group. None of the patients had received interferon therapy. Patients with other causes of CLD, chronic renal disease, diabetes, endocrinal hematological, and other debilitating diseases were excluded. All the patients studied were subjected to the following: complete medical history, full clinical examination, laboratory investigations including complete blood picture, liver function tests, fasting blood sugar, 2 h postprandial, HCV antibody and PCR for RNA of HCV; serum TPO level, abdominal ultrasonography, and liver biopsy for histopathological examination. Results Our Results showed a highly significant reduction in the platelet count in patients with CAH (192.55±41.02) and cirrhotic patients (159.800±86.189) in comparison with (322.67±38.12) the control group (P<0.01). There was nonsignificant increase in TPO in patients with CAH (115.93±71.66) and a significant decrease in TPO in cirrhotic patients (77.504±64.576) in comparison with (107.98±52.53) the control group. In the cirrhotic patients, there was a significant positive correlation between TPO and platelet count, whereas there was no correlation between TPO level and liver enzymes (alanine aminotransferase and aspartate aminotransferase) in all patients. In addition, a significant decrease in TPO was found in cirrhotic patients in comparison with CAH patients. Conclusion Serum TPO level was elevated in patients with chronic viral C hepatitis as a compensatory response to the reduction of platelet count with still functionally active liver cells, but as the disease progress to cirrhosis which also is associated with thrombocytopenia, TPO production is impaired, with failure to compensate the low platelet count aggravating thrombocytopenia