[en] [en] BACKGROUND: Identification of those at risk of more severe psoriasis and/or associated morbidities offers opportunity for early intervention, reduced disease burden and more cost-effective healthcare. Prognostic biomarkers of disease progression have thus been the focus of intense research, but none are part of routine practice.
OBJECTIVES: To identify and catalogue candidate biomarkers of disease progression in psoriasis for the translational research community.
METHODS: A systematic search of CENTRAL, Embase, LILACS and MEDLINE was performed for relevant articles published between 1990 and December 2021. Eligibility criteria were studies involving patients with psoriasis (any age, n ≥ 50) reporting biomarkers associated with disease progression. The main outcomes were any measure of skin severity or any prespecified psoriasis comorbidity. Data were extracted by one reviewer and checked by a second; studies meeting minimal quality criteria (longitudinal design and/or use of methods to control for confounding) were formally assessed for bias. Candidate biomarkers were identified by an expert multistakeholder group using a majority voting consensus exercise, and mapped to relevant cellular and molecular pathways.
RESULTS: Of 181 included studies, most investigated genomic or proteomic biomarkers associated with disease severity (n = 145) or psoriatic arthritis (n = 30). Methodological and reporting limitations compromised interpretation of findings, most notably a lack of longitudinal studies, and inadequate control for key prognostic factors. The following candidate biomarkers with future potential utility were identified for predicting disease severity: LCE3D, interleukin (IL)23R, IL23A, NFKBIL1 loci, HLA-C*06:02 (genomic), IL-17A, IgG aHDL, GlycA, I-FABP and kallikrein 8 (proteomic), tyramine (metabolomic); psoriatic arthritis: HLA-C*06:02, HLA-B*27, HLA-B*38, HLA-B*08, and variation at the IL23R and IL13 loci (genomic); IL-17A, CXCL10, Mac-2 binding protein, integrin b5, matrix metalloproteinase-3 and macrophage-colony stimulating factor (proteomic) and tyramine and mucic acid (metabolomic); and type 2 diabetes mellitus: variation in IL12B and IL23R loci (genomic). No biomarkers were supported by sufficient evidence for clinical use without further validation.
CONCLUSIONS: This review provides a comprehensive catalogue of investigated biomarkers of disease progression in psoriasis. Future studies must address the common methodological limitations identified herein to expedite discovery and validation of biomarkers for clinical use. What is already known about this topic? The current treatment paradigm in psoriasis is reactive. There is a need to develop effective risk-stratified management approaches that can proactively attenuate the substantial burden of disease. Prognostic biomarkers of disease progression have therefore been the focus of intense research. What does this study add? This review is the first to scope, collate and catalogue research investigating biomarkers of disease progression in psoriasis. The review identifies potentially promising candidate biomarkers for further investigation and highlights common important limitations that should be considered when designing and conducting future studies in this area.
Disciplines :
Immunology & infectious disease
Author, co-author :
Ramessur, Ravi ; St John's Institute of Dermatology, School of Basic & Medical Biosciences and Department of Medical & Molecular Genetics, School of Basic & Medical Biosciences, Faculty of Life Sciences & Medicine, King's College London, London, UK
Corbett, Mark; Centre for Reviews and Dissemination, University of York, York, UK
Marshall, David; Centre for Reviews and Dissemination, University of York, York, UK
Barbosa, Ines A; St John's Institute of Dermatology, School of Basic & Medical Biosciences and Department of Medical & Molecular Genetics, School of Basic & Medical Biosciences, Faculty of Life Sciences & Medicine, King's College London, London, UK
Dand, Nick ; St John's Institute of Dermatology, School of Basic & Medical Biosciences and Department of Medical & Molecular Genetics, School of Basic & Medical Biosciences, Faculty of Life Sciences & Medicine, King's College London, London, UK
Di Meglio, Paola ; St John's Institute of Dermatology, School of Basic & Medical Biosciences and Department of Medical & Molecular Genetics, School of Basic & Medical Biosciences, Faculty of Life Sciences & Medicine, King's College London, London, UK
Haddad, Salma; University College Hospital NHS Trust, London, UK
Jensen, Andreas H M ; University of Copenhagen, Copenhagen, Denmark
Koopmann, Witte; Department of Translational Medicine, LEO Pharma A/S, Ballerup, Denmark
Mahil, Satveer K; St John's Institute of Dermatology, School of Basic & Medical Biosciences and Department of Medical & Molecular Genetics, School of Basic & Medical Biosciences, Faculty of Life Sciences & Medicine, King's College London, London, UK
OSTASZEWSKI, Marek ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Bioinformatics Core
Rahmatulla, Seher ; West Hertfordshire NHS Trust, Hertfordshire, UK
Rastrick, Joe; Department of Immunology Research, UCB, Belgium
Saklatvala, Jake; St John's Institute of Dermatology, School of Basic & Medical Biosciences and Department of Medical & Molecular Genetics, School of Basic & Medical Biosciences, Faculty of Life Sciences & Medicine, King's College London, London, UK
Weidinger, Stephan ; Department of Dermatology and Allergy, University Hospital Schleswig-Holstein, Kiel, Germany
Wright, Kath; Centre for Reviews and Dissemination, University of York, York, UK
Eyerich, Kilian; Department of Dermatology and Allergy, Technical University of Munich, Munich, Germany ; Division of Dermatology, Department of Medicine, Karolinska Insitutet, Stockholm, Sweden
Ndlovu, Matladi; Department of Immunology Research, UCB, Belgium
Barker, Jonathan N; St John's Institute of Dermatology, School of Basic & Medical Biosciences and Department of Medical & Molecular Genetics, School of Basic & Medical Biosciences, Faculty of Life Sciences & Medicine, King's College London, London, UK
Skov, Lone ; Department of Dermatology and Allergy, Herlev and Gentofte Hospital, Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
Conrad, Curdin; Department of Dermatology, Lausanne University Hospital CHUV & University of Lausanne, Lausanne, Switzerland
Smith, Catherine H; St John's Institute of Dermatology, School of Basic & Medical Biosciences and Department of Medical & Molecular Genetics, School of Basic & Medical Biosciences, Faculty of Life Sciences & Medicine, King's College London, London, UK
Innovative Medicines Initiative 2 Joint Undertaking International Psoriasis Council NIHR Biomedical Research Centre (BRC) at King’s College London Innovative Medicines Initiative
Funding text :
This scoping review was supported and funded by the IPC and the BIOMAP consortium. This study was also supported by the Psoriasis Association, UK. The authors would like to thank Marta Vergnano for her contribution in title and abstract screening. The interactive map of psoriasis biomarkers is hosted by ELIXIR Luxembourg. Open access funding was enabled and organized by ProjektDEAL.S.K.M. has received departmental funding from AbbVie, Celgene, Eli Lilly, Janssen‐Cilag, Novartis, Sanofi and UCB. P.D.M. has received research grants from UCB and consultancy/speaker honoraria from Novartis, UCB and Janssen. K.E. has received honoraria and/or research grants from AbbVie, Almirall, Boehringer Ingelheim, Bristol Myers Squibb, Janssen, LEO Pharma, Lilly, Novartis, Pfizer and UCB. C.C. has received honoraria and/or research grants from AbbVie, Actelion, Almirall, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Janssen, LEO Pharma, Eli Lilly, MSD, Novartis, Pfizer, Samsung and UCB. J.N.B. has received honoraria and/or research grants from AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Janssen, LEO Pharma, Lilly, Novartis, Samsung and Sun Pharma. L.S. has received honoraria and/or research grants from AbbVie, Almirall, Bristol Myers Squibb, Celgene, Sanofi, UCB, Janssen, LEO Pharma, Lilly and Novartis. C.H.S. reports grants from an MRC‐funded stratified medicine consortium with multiple industry partners, grants from IMI (Horizon 2020)‐funded European consortium with multiple industry partners, and others from AbbVie, Novartis, Pfizer, Sanofi, Boehringer Ingelheim and SOBI, outside the submitted work; and is Chair of UK guidelines on biologic therapy in psoriasis.This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No 821511 (BIOMAP). The JU receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA. The research also received funding from the International Psoriasis Council, and support by the National Institute for Health and Care Research (NIHR) Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust and King's College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. S.K.M. is funded by a Medical Research Council Clinical Academic Research Partnership award (MR/T02383X/1). N.D. is funded by Health Data Research UK (MR/S003126/1).
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