| アブストラクト | Dupilumab, an IL-4/IL-13 receptor blocker, has been linked to emergent seronegative inflammatory arthritis and psoriasis that form part of the spondyloarthropathy spectrum. We systematically investigated patterns of immune disorders, including predominantly T helper 17(spondyloarthropathy pattern) and T helper 2mediated disorders and humoral autoimmune pattern diseases, using VigiBase, the World Health Organization's global pharmacovigilance of adverse drug reactions. Several bioinformatics databases and repositories were mined to couple dupilumab-related immunopharmacovigilance with molecular cascades relevant to reported findings. A total of 37,848 dupilumab adverse drug reaction cases were reported, with skin, eye, and musculoskeletal systems most affected. Seronegative arthritis (OR = 9.61), psoriasis (OR = 1.48), enthesitis/enthesopathy (OR = 12.65), and iridocyclitis (OR = 3.77) were highly associated. However, ankylosing spondylitis and inflammatory bowel disease were not conclusively associated. Overall, classic polygenic humoralmediated autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus were not associated with dupilumab use. Pathway analysis identified several biological pathways potentially involved in dupilumabassociated adverse drug reactions, including the fibroblast GF receptor (in particular, FGFR2) pathway. MicroRNAs analysis revealed the potential involvement of hsa-miR-21-5p and hsa-miR-335-5p. In conclusion, IL-4/IL-13 blockers are not unexpectedly protective against humoral autoimmune diseases but dynamically skew immune responses toward some IL-23/IL-17 cytokine pathwayrelated diseases. IL-4/13 axis also plays a role in homeostatic tissue repair and we noted evidence for a link with ocular and arterial pathology. |
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| 投稿者 | Bridgewood, Charlie; Wittmann, Miriam; Macleod, Tom; Watad, Abdulla; Newton, Darren; Bhan, Kanchan; Amital, Howard; Damiani, Giovanni; Giryes, Sami; Bragazzi, Nicola Luigi; McGonagle, Dennis |
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| 組織名 | Leeds Institute of Rheumatic and Musculoskeletal Medicine, School of Medicine,;University of Leeds, Leeds, United Kingdom.;University of Leeds, Leeds, United Kingdom; Leeds Biomedical Research Centre,;National Institute for Health Research, Leeds Teaching Hospitals NHS Trust,;Leeds, United Kingdom; Department of Dermatology, University Medical Center;Mainz, Mainz, Germany.;University of Leeds, Leeds, United Kingdom; Zabludowicz Center for Autoimmune;Diseases, Department of Medicine B., Sheba Medical Center, Ramat Gan, Israel;;Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Rheumatology;Unit, Sheba Medical Center, Ramat Gan, Israel.;Division of Haematology and Immunology, University of Leeds, Leeds, United;Kingdom.;Department of Ophthalmology, St James's University Hospital, Leeds, United;Zabludowicz Center for Autoimmune Diseases, Department of Medicine B., Sheba;Medical Center, Ramat Gan, Israel; Sackler Faculty of Medicine, Tel Aviv;University, Tel Aviv, Israel.;Department of Biomedical, Surgical and Dental Sciences, University of Milan,;Milan, Italy; Clinical Dermatology, Scientific Hospitalization and Treatment;Institute (IRCCS), Milan, Italy; PhD Degree Program in Pharmacological Sciences,;Department of Pharmaceutical and Pharmacological Sciences, University of Padua,;Padua, Italy.;University of Leeds, Leeds, United Kingdom; B. Shine Rheumatology Unit, Rambam;Health Care Campus, Haifa, Israel; The Ruth and Bruce Rappaport Faculty of;Medicine, Technion-Israel Institute of Technology, Haifa, Israel.;University of Leeds, Leeds, United Kingdom; Laboratory for Industrial and Applied;Mathematics (LIAM), Department of Mathematics and Statistics, Faculty of Science,;York University, Toronto, Ontario, Canada.;Leeds, United Kingdom. Electronic address: d.g.mcgonagle@leeds.ac.uk. |
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