49 results match your criteria: "University of Manchester and NIHR Manchester Biomedical Research Centre[Affiliation]"

Proceedings of the 2020 GRAPPA Collaborative Research Network (CRN) Meeting.

J Rheumatol

February 2021

As part of the supplement series GRAPPA 2020, this report was reviewed internally and approved by the Guest Editors for integrity, accuracy, and consistency with scientific and ethical standards. C. Stober, MBChB, MRCP, PhD, MSc, Department of Medicine, University of Cambridge, Cambridge, UK; D.R. Jadon, MBBCh, MRCP, PhD, University of Cambridge, Cambridge, UK; A.W. Armstrong, MD, PhD, Professor of Dermatology, Associate Dean for Clinical Research, Director of Clinical Research Support, Southern California Clinical and Translational Science Institute (SC CTSI), Vice Chair Director, Clinical Trials and Outcomes Research Director, Psoriasis Program, Department of Dermatology, Keck School of Medicine at USC, University of Southern California, Los Angeles, California, USA; V. Chandran, MD, DM, PhD, Department of Medicine, Division of Rheumatology, University of Toronto, Toronto Western Hospital, Krembil Research Institute, Toronto, Ontario, Canada; M. de Wit, PhD, GRAPPA Patient Research Partner, Department of Medical Humanities, Amsterdam University Medical Centre, Amsterdam, the Netherlands; P.S. Helliwell, MD, PhD Professor of Clinical Rheumatology, Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, NIHR Leeds Biomedical Research Centre, Leeds, UK; P.J. Mease, MD, Rheumatology Research, Swedish Medical Center/ Providence St. Joseph Health and University of Washington School of Medicine, Seattle, Washington, USA; A. Ogdie, MD, MSCE, Associate Professor of Medicine and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA; D. O'Sullivan, BE, GRAPPA Patient Research Partner, Our Lady's Hospice & Care Services, Rheumatic & Musculoskeletal Disease Unit, Dublin, Ireland; S.R. Pennington, PhD, School of Medicine, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin, Ireland; T. Löve, MD, PhD, Faculty of Medicine, University of Iceland, and Department of Research, Landspitali University Hospital, Reykjavik, Iceland; A. Cauli, MD, PhD, Rheumatology Unit, University Clinic and AOU of Cagliari, Monserrato, Italy; L. van Mens, MD, PhD, Amsterdam University Medical Centers/University of Amsterdam, Department of Clinical Immunology and Rheumatology Amsterdam, Infection & Immunity Institute, Amsterdam, the Netherlands; R. Waxman, MPH, Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Harehills Lane, Leeds, and NIHR Leeds Biomedical Research Centre, Leeds, UK; J.U. Scher, MD, Department of Medicine, NYU Grossman School of Medicine, New York, New York, USA; A. Barton, MBChB, MSc, PhD, FRCP, Centre for Musculoskeletal Research, The University of Manchester and NIHR Manchester Biomedical Research Centre, Manchester University NHS Trust, Manchester, UK; C.T. Ritchlin, MD, MPH, Professor of Medicine, Division of Allergy, Immunology and Rheumatology, University of Rochester Medical Center, Rochester, New York, USA; O. FitzGerald, MD, FRCPI, FRCP, Consultant Rheumatologist and Newman Clinical Research Professor, Conway Institute for Biomolecular Research, University College Dublin, Dublin, Ireland. AA has received research funding from Boehringer Ingelheim/Parexel, Bristol Myers Squibb, Dermavant, Dermira, Eli Lilly, Galderma, Janssen-Ortho Inc., Kyowa Hakko Kirin, Leo Pharma, Pfizer Inc., Sanofi Genzyme, UCB Pharma; and honorariums from AbbVie, Bristol Myers Squibb, Dermavant, Eli Lilly, Janssen Pharmaceuticals Inc., Leo Pharma, Modernizing Medicine, Novartis Pharmaceuticals Corp., Ortho Dermatologics, Pfizer Inc., Regeneron Pharmaceuticals, Sanofi Genzyme, and Sun Pharma. VC has received consulting fees and/or speaking fees and/or honoraria from AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly and Company, Janssen, Novartis, Pfizer, and UCB, and his spouse is an employee of Eli Lilly and Company. PJM has received research grants, consultation fees, and/or speaker honoraria from AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer, Sun Pharma, and UCB. JUS has received research grants and/or consulting fees from AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Janssen, Novartis, Pfizer Inc, Sanofi, and UCB; OF has received research grants and/ or consulting fees from AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer Inc., and UCB. All other coauthors declare no conflicts of interest. Address correspondence to Prof. Oliver FitzGerald, School of Medicine, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield Dublin 4, Ireland. Email:

At the 2020 Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA)- Collaborative Research Network (CRN) annual meeting, the GRAPPA-CRN group presented a pilot investigator-initiated study protocol to test electronic case report forms (eCRFs) and proposed Standardized Operating Procedures (SOPs) to evaluate biomarkers of psoriatic arthritis (PsA) associated with axial disease. The progress on 3 studies was also presented: BioDAM PsA (Biomarkers as Predictors of structural DAMage in PsA; to validate soluble biomarkers as predictors of structural damage in PsA), PreventPsA (examining the development of PsA and risk factors among patients with psoriasis and no arthritis), and PredictORPsA (Predicting Treatment respOnse in patients with eaRly PsA; in collaboration with Pfizer using samples from the Oral Psoriatic Arthritis TriaL [OPAL], to identify biomarkers of treatment response). GRAPPA-CRN funding partnerships and applications are also underway with both the Innovative Medicines Initiative (IMI) in Europe and Accelerating Medicines Partnerships (AMP) 2.

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Organ culture of microdissected scalp hair follicles (HFs) has become the gold standard for human ex vivo hair research; however, availability is becoming very limited. Although various simplistic "HF-equivalent" in vitro models have been developed to overcome this limitation, they often fail to sufficiently mimic the complex cell-cell and cell-matrix interactions between epithelial and mesenchymal cell populations that underlie the specific growth processes occurring in a native HF. Here, we have attempted to overcome these limitations by developing a novel human hair research model that combines dermal papilla (DP) fibroblasts, cultured as 3-dimensional (3D) spheroids (DPS), with plucked anagen hair shafts (HS).

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Mouse models for atopic dermatitis (AD) are an indispensable preclinical research tool for testing new candidate AD therapeutics and for interrogating AD pathobiology in vivo. In this Viewpoint, we delineate why, unfortunately, none of the currently available so-called "AD" mouse models satisfactorily reflect the clinical complexity of human AD, but imitate more "allergic" or "irriant" contact dermatitis conditions. This limits the predictive value of AD models for clinical outcomes of new tested candidate AD therapeutics and the instructiveness of mouse models for human AD pathophysiology research.

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Objective: SLE is characterized by relapses and remissions. We aimed to describe the frequency, type and time to flare in a cohort of SLE patients.

Methods: SLE patients with one or more 'A' or 'B' BILAG-2004 systems meeting flare criteria ('new' or 'worse' items) and requiring an increase in immunosuppression were recruited from nine UK centres and assessed at baseline and monthly for 9 months.

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Background: The efficacy of biologic therapies is greater among biologic-naïve vs. biologic-experienced psoriasis patients. However, little is known as to whether prior use of other systemic therapies impacts secukinumab efficacy in patients with moderate-to-severe psoriasis.

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Anagen stage hair follicles (HFs) exhibit "immune privilege (IP)" from the level of the bulge downwards to the bulb. Both passive and active IP mechanisms protect HFs from physiologically undesired immune responses and limit immune surveillance. IP is relative, not absolute, and is primarily based on absent, or greatly reduced, intra-follicular antigen presentation via MHC class I and II molecules, along with prominent expression of "no danger" signals like CD200 and the creation of an immunoinhibitory signalling milieu generated by the secretory activities of HFs.

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Impaired cutaneous wound healing remains a major healthcare challenge. The enormity of this challenge is compounded by the lack of preclinical human skin wound healing models that recapitulate selected key factors underlying impaired healing, namely hypoxia/poor tissue perfusion, oxidative damage, defective innervation, and hyperglycaemia. Since organ-cultured human skin already represents a denervated and impaired perfusion state, we sought to further mimic "pathological" wound healing conditions by culturing experimentally wounded, healthy full-thickness frontotemporal skin from three healthy female subjects for three days in either serum-free supplemented Williams' E medium or in unsupplemented medium under "pathological" conditions (i.

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Toward Predicting the Spatio-Temporal Dynamics of Alopecia Areata Lesions Using Partial Differential Equation Analysis.

Bull Math Biol

February 2020

Department of Mathematics, Florida State University, 208 Love Building, 1017 Academic Way, Tallahassee, FL, 32306, USA.

Hair loss in the autoimmune disease, alopecia areata (AA), is characterized by the appearance of circularly spreading alopecic lesions in seemingly healthy skin. The distinct spatial patterns of AA lesions form because the immune system attacks hair follicle cells that are in the process of producing hair shaft, catapults the mini-organs that produce hair from a state of growth (anagen) into an apoptosis-driven regression state (catagen), and causes major hair follicle dystrophy along with rapid hair shaft shedding. In this paper, we develop a model of partial differential equations (PDEs) to describe the spatio-temporal dynamics of immune system components that clinical and experimental studies show are primarily involved in the disease development.

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Background: Type I interferons are involved in systemic lupus erythematosus (SLE) pathogenesis. In a phase 2 trial, anifrolumab, a human monoclonal antibody to type I interferon receptor subunit 1, suppressed interferon gene signatures and substantially reduced SLE disease activity. Here, we sought to confirm the efficacy of anifrolumab versus placebo in a phase 3 trial of adult patients with SLE and moderate-to-severe disease activity despite standard-of-care treatment.

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Soluble urokinase plasminogen activator receptor (suPAR) levels predict damage accrual in patients with recent-onset systemic lupus erythematosus.

J Autoimmun

January 2020

Rheumatology/Division of Neuro and Inflammation Sciences, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.

Objective: The soluble urokinase plasminogen activator receptor (suPAR) has potential as a prognosis and severity biomarker in several inflammatory and infectious diseases. In a previous cross-sectional study, suPAR levels were shown to reflect damage accrual in cases of systemic lupus erythematosus (SLE). Herein, we evaluated suPAR as a predictor of future organ damage in recent-onset SLE.

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Frontiers in alopecia areata pathobiology research.

J Allergy Clin Immunol

December 2019

Dr Philipp Frost Department of Dermatology & Cutaneous Surgery, Miller School of Medicine, University of Miami, Miami, Fla; Dermatology Research Centre, University of Manchester and NIHR Manchester Biomedical Research Centre, Manchester, United Kingdom.

This current review explores selected and as yet insufficiently investigated frontiers in current alopecia areata (AA) pathobiology research, with an emphasis on potential "new" players in AA pathobiology that deserve more systematic exploration and therapeutic targeting. Indeed, new evidence suggests that CD8 T cells, which have long been thought to be the central players in AA pathobiology, are not the only drivers of disease. Instead, subsets of natural killer (NK) and so-called "unconventional" T cells (invariant NK T cells, γδ T cells, classic NK cells, and type 1 innate lymphoid cells), all of which can produce large amounts of IFN-γ, might also drive AA pathobiology independent of classical, autoantigen-dependent CD8 T-cell functions.

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Contraindications to immunotherapy: a global approach.

Clin Transl Allergy

September 2019

14Département de Pneumologie et Addictologie, Hôpital Arnaud de Villeneuve, University Hospital of Montpellier, Montpellier, France.

Background: Recommendations on contraindications to allergen immunotherapy (AIT) have been independently developed by National and International Societies/Academies. AIT contraindications are mainly based on case reports, case-series, or experts' opinion, while evidence-based information is limited. The aim of the present review was to describe existing guidelines on contraindications to AIT and to highlight differences between them.

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Background: Given that unwanted hair growth (hirsutism, hypertrichosis) can cause major psychological distress, new pharmacological treatment strategies with safe and effective hair growth inhibitors that do not destroy the hair follicle (HF) and its stem cells need to be developed.

Objectives: To establish if osteopontin-derived fragments may modulate human hair growth given that human HFs express the multifunctional, immunomodulatory glycoprotein, osteopontin.

Methods: Our hypothesis was tested ex vivo and in vivo by using a newly generated, toxicologically well-characterized, modified osteopontin-derived peptide (FOL-005), which binds to the HF.

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Introduction: Belimumab, an anti-B-lymphocyte-stimulator antibody, is approved for the treatment of active, autoantibody-positive systemic lupus erythematosus (SLE). Rituximab, a B cell-depleting anti-CD20 antibody, remains in the SLE treatment armamentarium despite failed trials in lupus nephritis and extrarenal lupus. These biologics, which operate through complementary mechanisms, might result in an enhanced depletion of circulating and tissue-resident autoreactive B lymphocytes when administered together.

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JAK inhibitors and alopecia areata.

Lancet

January 2019

Department of Dermatology & Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL, USA; Centre for Dermatology Research, University of Manchester and NIHR Manchester Biomedical Research Centre, Manchester, UK.

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Osteopontin and Disease Activity in Patients with Recent-onset Systemic Lupus Erythematosus: Results from the SLICC Inception Cohort.

J Rheumatol

May 2019

From the Rheumatology/Division of Neuro and Inflammation Sciences, Department of Clinical and Experimental Medicine, Linköping University, Linköping; Department of Medicine, Unit of Rheumatology, Karolinska Institutet and Karolinska University Hospital, Stockholm; Department of Clinical Sciences Lund, Section of Rheumatology, Lund University, Lund; Unit for Clinical Therapy Research (ClinTRID), Karolinska University, Stockholm, Sweden; Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital and University of Toronto, Toronto, Ontario; Division of Rheumatology, Centre Hospitalier Universitaire (CHU) de Québec - Université Laval, Quebec City, Quebec; Division of Rheumatology, Cumming School of Medicine - University of Calgary, Calgary, Alberta; Division of Rheumatology, Department of Medicine, McGill University Health Centre, Montreal, Quebec; Division of Rheumatology, Department of Medicine and Department of Pathology, Queen Elizabeth II Health Sciences Centre and Dalhousie University, Halifax, Nova Scotia; Department of Medicine and Community Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada; Instituto Nacional de Ciencias Médicas y Nutrición, Mexico City, Mexico; Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea; Rheumatology Research Group, School of Immunity and Infection, College of Medical and Dental Sciences, University of Birmingham, Birmingham; Centre for Rheumatology Research, University College, London; Lupus Research Unit, The Rayne Institute, St. Thomas' Hospital, King's College London School of Medicine, London; Lanarkshire Centre for Rheumatology, Hairmyres Hospital, East Kilbride, Scotland; Arthritis Research UK Centre for Epidemiology, Centre for Musculoskeletal Research, Faculty of Biology, Medicine and Health, The University of Manchester and UK National Institute for Health Research (NIHR) Manchester Biomedical Research Centre, Manchester University Foundation Trust, Manchester, UK; Cedars-Sinai/David Geffen School of Medicine at University of California at Los Angeles, Los Angeles, California; Department of Clinical Pharmacology, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma; Department of Medicine, State University of New York (SUNY) Downstate Medical Center, Brooklyn, New York; Department of Medicine, Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, Alabama; Department of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, Maryland; Feinstein Institute for Medical Research, Manhasset, New York; Division of Rheumatology and Immunology, Department of Medicine, University of North Carolina, Chapel Hill, North Carolina; Autoimmunity Institute, Allegheny Health Network, Pittsburgh, Pennsylvania; Northwestern University and Feinberg School of Medicine, Chicago, Illinois; Division of Rheumatology, Emory University School of Medicine, Atlanta, Georgia; University of California San Diego School of Medicine, La Jolla, California; Division of Rheumatology, Medical University of South Carolina, Charleston, South Carolina; Division of Rheumatology, Columbia University Medical Center, New York, New York, USA; Department of Rheumatology, Center for Rheumatology Research Fossvogur Landspitali University Hospital, Reyjkavik, Iceland; Autoimmune Disease Unit, Department of Internal Medicine, Hospital Universitario Cruces, BioCruces Health Research Institute, University of the Basque Country, Barakaldo; Josep Font Autoimmune Diseases Laboratory, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Department of Autoimmune Diseases, Hospital Clínic, Barcelona, Spain; Division of Rheumatology, Department of Internal Medicine, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey; Copenhagen Lupus and Vasculitis Clinic, Centre for Rheumatology and Spine Diseases, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark; Department of Rheumatology, Kantousspital, Schaffhausen, Switzerland.

Objective: In cross-sectional studies, elevated osteopontin (OPN) levels have been proposed to reflect, and/or precede, progressive organ damage and disease severity in systemic lupus erythematosus (SLE). We aimed, in a cohort of patients with recent-onset SLE, to determine whether raised serum OPN levels precede damage and/or are associated with disease activity or certain disease phenotypes.

Methods: We included 344 patients from the Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort who had 5 years of followup data available.

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Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a considerable impact on patients' quality of life. Despite the plethora of clinical trials for SLE since the turn of the millennium, only one new treatment has been approved for the condition, and the overall pace of successful drug development remains slow. Nevertheless, the myriad of clinical studies has yielded insights that have informed and refined our understanding of eligibility criteria, outcome measures and trial design in SLE.

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Background: Patients with systemic lupus erythematosus have substantial unmet medical need. Baricitinib is an oral selective Janus kinase (JAK)1 and JAK2 inhibitor that we hypothesised might have therapeutic benefit in patients with systemic lupus erythematosus.

Methods: In this double-blind, multicentre, randomised, placebo-controlled, 24-week phase 2 study, patients were recruited from 78 centres in 11 countries.

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Peroxisome Proliferator-Activated Receptor-γ-Mediated Signaling Regulates Mitochondrial Energy Metabolism in Human Hair Follicle Epithelium.

J Invest Dermatol

July 2018

Center for Dermatology Research, University of Manchester and NIHR Manchester Biomedical Research Centre, Manchester, UK; Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL, USA. Electronic address:

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Sleep in adolescents and young adults.

Clin Med (Lond)

October 2017

Central Manchester University Hospitals NHS Foundation Trust, Arthritis Research UK Centre for Epidemiology, Centre for Musculoskeletal Research, Manchester Academic Health Science Centre, University of Manchester and NIHR Manchester Biomedical Research Centre, Central Manchester NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.

Sleep has an important role in maintaining health and wellbeing; this relationship is becoming increasingly recognised for adolescents and young adults. Many physicians will encounter young people who present with complaints or conditions that have some relation to poor sleep. This review article looks at why sleep matters within this population group, how it can impact on longer term health consequences and discusses some tools to help enable the clinician to evaluate and address sleep within clinical practice.

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