Toward cellular biomarkers for rheumatoid arthritis: Biomarkers in RA

This editorial refers to Differential effects of biological DMARDs on peripheral immune cell phenotypes in patients with rheumatoid arthritis

Library support for systematic reviews at the London School of Hygiene & Tropical Medicine

Systematic reviews are well established in evidence-based medicine, where experimental results are used to support decision making. The methodology is gradually spreading to other subject areas, including the social sciences, with the support of organisations such as the Campbell Collaboration1 and the EPPI Centre2. This paper describes the support provided to systematic reviewers at the London School of Hygiene & Tropical Medicine by Library & Archives Service staff. A systematic review is a specific type of literature review. A clear question is set before comprehensive and transparent methods are used to identify, select and evaluate all of the relevant research. Data is then collected and analysed from each included study to provide unbiased summaries of the results. In this way, reliable evidence-based reviews can be produced and readers can have confidence in the conclusions drawn. The PRISMA Statement (Moher et al., 2009) has been developed to make sure that all relevant methodological information is included in the published review, and can also be used to guide reviewers through the systematic review process. It is useful when helping reviewers as it provides minimum standards for each stage of the review process, including the literature searching and study selection process

Reduced TCR-dependent activation through citrullination of a T-cell epitope enhances Th17 development by disruption of the STAT3/5 balance

Citrullination is a post-translational modification of arginine that commonly occurs in inflammatory tissues. Because T-cell receptor (TCR) signal quantity and quality can regulate T-cell differentiation, citrullination within a T-cell epitope has potential implications for T-cell effector function. Here, we investigated how citrullination of an immunedominant T-cell epitope affected Th17 development. Murine na¨ıve CD4+ T cells with a transgenic TCR recognising p89-103 of the G1 domain of aggrecan (agg) were co-cultured with syngeneic bone marrow-derived dendritic cells (BMDC) presenting the native or citrullinated peptides. In the presence of pro-Th17 cytokines, the peptide citrullinated on residue 93 (R93Cit) significantly enhanced Th17 development whilst impairing the Th2 response, compared to the native peptide. T cells responding to R93Cit produced less IL-2, expressed lower levels of the IL-2 receptor subunit CD25, and showed reduced STAT5 phosphorylation, whilst STAT3 activation was unaltered. IL-2 blockade in native p89-103-primed T cells enhanced the phosphorylated STAT3/STAT5 ratio, and concomitantly enhanced Th17 development. Our data illustrate how a post-translational modification of a TCR contact point may promote Th17 development by altering the balance between STAT5 and STAT3 activation in responding T cells, and provide new insight into how protein citrullination may influence effector Th-cell development in inflammatory disorders

Synovial cell metabolism and chronic inflammation in rheumatoid arthritis

Metabolomic studies of body fluids show that immune-mediated inflammatory diseases such as rheumatoid arthritis (RA) are associated with metabolic disruption. This is likely to reflect the increased bioenergetic and biosynthetic demands of sustained inflammation and changes to nutrient and oxygen availability in damaged tissue. The synovial membrane lining layer is the principle site of inflammation in RA. Here the resident cells are the fibroblast-like synoviocytes (FLS) and the synovial tissue macrophages (STM), which are transformed toward overproduction of enzymes which degrade cartilage and bone, and cytokines which promote immune cell infiltration. Recent studies have shown metabolic changes in both FLS and macrophages from RA patients and these may be therapeutically targetable. However, as the origins and subset specific functions of synoviocytes are poorly understood and the signaling modules which control metabolic deviation in RA synovial cells are yet to be explored, significant additional research is needed to translate these findings toward clinical application. Furthermore, in many inflamed tissues, different cell types can forge metabolic collaborations through solute carriers (SLC) in their membranes, to meet a high demand for energy or biomolecules. Such relationships are likely to exist in the synovium and are yet to be explored. Finally, it is not yet known whether metabolic change is a consequence of disease or if primary changes to cellular metabolism might underlie or contribute to early stage disease pathogenesis. This article collates what is known about metabolism in synovial tissue cells and highlights future research directions in this area

Technologies, strategies and approaches for testing populations at risk of sexually transmitted infections: a systematic review protocol to inform prevention and control in EU/EEA countries.

OBJECTIVES: This protocol outlines a systematic review methodology, aiming to assess the recent evidence-base for the impact of testing strategies and approaches on access to testing, testing coverage, and linkage to care for populations at risk for specific curable sexually transmitted infections (STIs) (chlamydia, gonorrhoea, syphilis, trichomoniasis, and Mycoplasma genitalium infections). DATA SOURCES: These include MEDLINE, Embase, PsycINFO, Global Health, Cochrane Database, Epistemonikos, CINAHL Plus, and Web of Science Core Collection. REVIEW METHODS: Papers reporting primary data from 1 January 2012 onwards will be included. Titles, abstracts, and full texts will be reviewed for inclusion, and data will be extracted using a pre-specified and piloted data extraction form, by two independent reviewers. Experts in the field will be contacted and interviewed for further information about ongoing or unpublished studies. A narrative synthesis of the findings will be conducted. DISCUSSION: Outcomes of this study will inform policy makers, national and international programme coordinators, public health and clinical experts, and civil society organisations involved in STI prevention and control in EU/EEA countries and elsewhere. The review will provide a direction for future researchers and programmers seeking to improve STI testing services among key populations at high risk for STIs. SYSTEMATIC REVIEW REGISTRATION: In accordance with guidelines outlined in the PRISMA-P methodology, this protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) on 30 January 2019: CRD42019118261

A journal club for professional networking and promotion of systematic review methodology

This article describes the launching of a journal club in the EAHIL Special Interest Group (SIG) for Evidence- Based Information. The key aim of the SIG is to bring together and connect all EAHIL members wanting to improve the quality of systematic reviews and other evidence-based products. One project was to set up a reference library with research papers on systematic review methodology and the role of librarians. To help translate research into practice and connect colleagues for discussion, a journal club was launched. Invited guests, such as the authors of a selected paper, not only information specialists, have been a successful feature and future development of the journal club may include inviting other authors such as students, PhD students or clinicians