PMID- 36281753 OWN - NLM STAT- MEDLINE DCOM- 20230517 LR - 20230522 IS - 2326-5205 (Electronic) IS - 2326-5191 (Linking) VI - 75 IP - 5 DP - 2023 May TI - Identification of a Distinct Monocyte-Driven Signature in Systemic Sclerosis Using Biophysical Phenotyping of Circulating Immune Cells. PG - 768-781 LID - 10.1002/art.42394 [doi] AB - OBJECTIVE: Pathologically activated circulating immune cells, including monocytes, play major roles in systemic sclerosis (SSc). Their functional characterization can provide crucial information with direct clinical relevance. However, tools for the evaluation of pathologic immune cell activation and, in general, of clinical outcomes in SSc are scarce. Biophysical phenotyping (including characterization of cell mechanics and morphology) provides access to a novel, mostly unexplored layer of information regarding pathophysiologic immune cell activation. We hypothesized that the biophysical phenotyping of circulating immune cells, reflecting their pathologic activation, can be used as a clinical tool for the evaluation and risk stratification of patients with SSc. METHODS: We performed biophysical phenotyping of circulating immune cells by real-time fluorescence and deformability cytometry (RT-FDC) in 63 SSc patients, 59 rheumatoid arthritis (RA) patients, 28 antineutrophil cytoplasmic antibody-associated vasculitis (AAV) patients, and 22 age- and sex-matched healthy donors. RESULTS: We identified a specific signature of biophysical properties of circulating immune cells in SSc patients that was mainly driven by monocytes. Since it is absent in RA and AAV, this signature reflects an SSc-specific monocyte activation rather than general inflammation. The biophysical properties of monocytes indicate current disease activity, the extent of skin or lung fibrosis, and the severity of manifestations of microvascular damage, as well as the risk of disease progression in SSc patients. CONCLUSION: Changes in the biophysical properties of circulating immune cells reflect their pathologic activation in SSc patients and are associated with clinical outcomes. As a high-throughput approach that requires minimal preparations, RT-FDC-based biophysical phenotyping of monocytes can serve as a tool for the evaluation and risk stratification of patients with SSc. CI - (c) 2022 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology. FAU - Matei, Alexandru-Emil AU - Matei AE AUID- ORCID: 0000-0003-1248-3145 AD - Department of Rheumatology and Hiller Research Unit, University Hospital Dusseldorf, Medical Faculty of Heinrich Heine University, Dusseldorf, Germany, and Department of Internal Medicine 3-Rheumatology and Immunology and Deutsches Zentrum Immuntherapie (DZI), Friedrich-Alexander University Erlangen-Nurnberg (FAU), and Universitatsklinikum Erlangen, Erlangen, Germany. FAU - Kubankova, Marketa AU - Kubankova M AD - Max Planck Institute for the Science of Light & Max-Planck-Center fur Physik und Medizin, Erlangen, Germany, and Biotechnology Center, Center for Molecular and Cellular Bioengineering, Technische Universitat Dresden, Dresden, Germany. FAU - Xu, Liyan AU - Xu L AD - Department of Rheumatology and Hiller Research Unit, University Hospital Dusseldorf, Medical Faculty of Heinrich Heine University, Dusseldorf, Germany, and Department of Internal Medicine 3-Rheumatology and Immunology and Deutsches Zentrum Immuntherapie (DZI), Friedrich-Alexander University Erlangen-Nurnberg (FAU), and Universitatsklinikum Erlangen, Erlangen, Germany. FAU - Gyorfi, Andrea-Hermina AU - Gyorfi AH AD - Department of Rheumatology and Hiller Research Unit, University Hospital Dusseldorf, Medical Faculty of Heinrich Heine University, Dusseldorf, Germany, and Department of Internal Medicine 3-Rheumatology and Immunology and Deutsches Zentrum Immuntherapie (DZI), Friedrich-Alexander University Erlangen-Nurnberg (FAU), and Universitatsklinikum Erlangen, Erlangen, Germany. FAU - Boxberger, Evgenia AU - Boxberger E AD - Department of Internal Medicine 3-Rheumatology and Immunology and Deutsches Zentrum Immuntherapie (DZI), Friedrich-Alexander-University Erlangen-Nurnberg (FAU) and Universitatsklinikum Erlangen, Erlangen, Germany. FAU - Soteriou, Despina AU - Soteriou D AD - Max Planck Institute for the Science of Light & Max-Planck-Center fur Physik und Medizin, Erlangen, Germany. FAU - Papava, Maria AU - Papava M AD - Department of Internal Medicine 3-Rheumatology and Immunology and Deutsches Zentrum Immuntherapie (DZI), Friedrich-Alexander-University Erlangen-Nurnberg (FAU) and Universitatsklinikum Erlangen, Erlangen, Germany. FAU - Prater, Julia AU - Prater J AD - Department of Internal Medicine 3-Rheumatology and Immunology and Deutsches Zentrum Immuntherapie (DZI), Friedrich-Alexander-University Erlangen-Nurnberg (FAU) and Universitatsklinikum Erlangen, Erlangen, Germany. FAU - Hong, Xuezhi AU - Hong X AD - Department of Rheumatology and Hiller Research Unit, University Hospital Dusseldorf, Medical Faculty of Heinrich Heine University, Dusseldorf, Germany, and Department of Internal Medicine 3-Rheumatology and Immunology and Deutsches Zentrum Immuntherapie (DZI), Friedrich-Alexander University Erlangen-Nurnberg (FAU), and Universitatsklinikum Erlangen, Erlangen, Germany. FAU - Bergmann, Christina AU - Bergmann C AUID- ORCID: 0000-0001-5257-9171 AD - Department of Internal Medicine 3-Rheumatology and Immunology and Deutsches Zentrum Immuntherapie (DZI), Friedrich-Alexander-University Erlangen-Nurnberg (FAU) and Universitatsklinikum Erlangen, Erlangen, Germany. FAU - Krater, Martin AU - Krater M AD - Max Planck Institute for the Science of Light & Max-Planck-Center fur Physik und Medizin, Erlangen, Germany, and Biotechnology Center, Center for Molecular and Cellular Bioengineering, Technische Universitat Dresden, Dresden, Germany. FAU - Schett, Georg AU - Schett G AUID- ORCID: 0000-0001-8740-9615 AD - Department of Internal Medicine 3-Rheumatology and Immunology and Deutsches Zentrum Immuntherapie (DZI), Friedrich-Alexander-University Erlangen-Nurnberg (FAU) and Universitatsklinikum Erlangen, Erlangen, Germany. FAU - Guck, Jochen AU - Guck J AD - Max Planck Institute for the Science of Light & Max-Planck-Center fur Physik und Medizin, Erlangen, Germany, and Biotechnology Center, Center for Molecular and Cellular Bioengineering, Technische Universitat Dresden, Dresden, Germany. FAU - Distler, Jorg H W AU - Distler JHW AUID- ORCID: 0000-0001-7408-9333 AD - Department of Rheumatology and Hiller Research Unit, University Hospital Dusseldorf, Medical Faculty of Heinrich Heine University, Dusseldorf, Germany, and Department of Internal Medicine 3-Rheumatology and Immunology and Deutsches Zentrum Immuntherapie (DZI), Friedrich-Alexander University Erlangen-Nurnberg (FAU), and Universitatsklinikum Erlangen, Erlangen, Germany. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230320 PL - United States TA - Arthritis Rheumatol JT - Arthritis & rheumatology (Hoboken, N.J.) JID - 101623795 SB - IM MH - Humans MH - Monocytes MH - *Scleroderma, Systemic/complications MH - *Pulmonary Fibrosis/pathology MH - Skin/pathology MH - *Arthritis, Rheumatoid EDAT- 2022/10/26 06:00 MHDA- 2023/05/17 06:42 CRDT- 2022/10/25 04:53 PHST- 2022/09/08 00:00 [revised] PHST- 2022/02/02 00:00 [received] PHST- 2022/10/18 00:00 [accepted] PHST- 2023/05/17 06:42 [medline] PHST- 2022/10/26 06:00 [pubmed] PHST- 2022/10/25 04:53 [entrez] AID - 10.1002/art.42394 [doi] PST - ppublish SO - Arthritis Rheumatol. 2023 May;75(5):768-781. doi: 10.1002/art.42394. Epub 2023 Mar 20.