I021 The pathogenesis (aetiology and immunity) of systemic IgG4-RD and treatments of the future

Rheumatology, Apr 2019

Culver, Emma

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I021 The pathogenesis (aetiology and immunity) of systemic IgG4-RD and treatments of the future

Emma Culver 0 1 Unit, University of Southampton, 0 Gastroenterology, University of Oxford , Oxford , United Kingdom 1 for Primary Care and Health Sciences, Keele University , Keele , United Kingdom OF THE TRANSITION FROM IN MUSCULOSKELETAL PRIMARY THE RHEUMATOLOGY CLINIC D o w n l o a d e d fr o m - believed to resolve by late teens/early 20s, although patients can often have a longer disease duration well into adulthood. Patients may also develop a clinical picture more compatible with a sero-negative spondyloathropathy. Disclosures: E. Culver: Honoraria; Xencor, Falk, Strategen. Grants/ research support; Merck. Immunoglobulin G4-related disease (IgG4-RD) is a multi-organ fibroinflammatory condition with a ?stratified pathology? in affected tissues, characterised by a lymphoplasmacytic infiltrate with abundant IgG4? plasma cells and a storiform pattern of fibrosis. Important immunological insights have evolved to include clonal expansions of activated plasmablasts, CD4? cytotoxic inflammatory and pro-fibrotic lymphocytes, and lesional activated T-follicular helper (Tfh) cells in the disease. The remarkable efficacy of B cell depletion (Rituximab) in these patients supports an important pathogenic role of B cell/T cell collaboration. A number of unsolved questions remain, including the identification of an antigenic trigger(s), the implications of IgG4 antibodies for pathophysiology, and the precise immunological mechanisms leading to fibrosis. Combining data from next generation sequencing, single cell RNA sequencing, and protein expression has illuminated a variety of potential targeted therapeutic strategies. These include B cell inhibition with XmAb5871, co-stimulatory blockade with Abatacept, targeting of cytotoxic CD4? lymphocytes, and ICOSdirected Tfh cell inhibition. will use the principles outlined above to consider an effective communication strategy, targeting different outputs for different audiences. Finally, we will consider how to sustain the effect of these campaigns. This session is relevant to all healthcare professionals and patients, and should improve understanding of co-design principles whether this be for service or policymaking. Disclosures: L. Swaithes: Grants/research support; LS has received funding from the NIHR for the Short Placement Award for Research Collaboration Award. Significant delays exist in translating research findings into clinical practice. On average there is a 17-year lag from completing a research study to the outcomes of the research benefiting patients and only 14% of research is implemented in clinical practice. Various strategies have been developed to accelerate the implementation of research into usable innovations in the real world. For example, the evidencebased practice movement, the development of clinical guidelines, a recent synthesis of NIHR systematic reviews, and a growing body of implementation research and theories to support these initiatives. Despite this, a gap remains between utilizing such strategies in everyday practice to exploit the evidence and optimise the uptake of innovations in the real world. Using lessons learnt from a trial implementing the NICE guidelines for osteoarthritis in primary care, this session will present the reality of how this evidence was used in real world practice. Qualitative research for developing a toolkit for use in closing the evidence-to-practice gap will also be presented and the implications for rheumatology conditions will be discussed. This session is relevant to individuals and groups who are at the interface between research and innovation in the NHS and aims to help them to navigate them through this complexity. I025 LEARNING FROM INFLUENCING THE COMMISSIONING HEALTH study, alongside examples from service improvement and research, principles to enhance the likely application of knowledge will be addressed. These will include priority setting, defining and mapping stakeholders, and an understanding of the differences between the principles of co-design and stakeholder consultation. Moving on to consider the means by which to maximise dissemination efforts, we Research, University of the West of from NIHR support; NW currently HS&DR; NIHR RfPB; an overview of what is meant by and how innovative strategies can be process, and maximise the evidence to clinical practice. It will hierarchical approaches to evidence alternative, robust strategies that basis for implementation decisions. how collaborative working between the KM through the generation of and better evidence informed h t t p s : / / a c a d e m i c . o u p . c o m /r h e u m a t o l o g y / a itr c l e a b s tr a c t / 5 8 / S u p p l e m e n t _ 3 / k e z 1 0 9 . 0 2 0 / 5 4 4 4 6 1 8 b y g u e s t o n 0 3 M a y 2 0 1 9


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Culver, Emma. I021 The pathogenesis (aetiology and immunity) of systemic IgG4-RD and treatments of the future, Rheumatology, 2019, DOI: 10.1093/rheumatology/kez109.020