{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T13:47:10Z","timestamp":1787060830280,"version":"build-2736575974"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2019,5,1]],"date-time":"2019-05-01T00:00:00Z","timestamp":1556668800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,5,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Polystyrene beads are broadly applied in flow cytometry. Implementing bead-based assays in mass cytometry is desired but hampered by the lack of an elemental label required for their detection. In this study, we introduce stable osmium tetroxide labeling as a universal approach for generating functionalized beads readily detectable by mass cytometry. We demonstrate the utility of osmium-labeled beads for signal spillover compensation in mass cytometry, and, strikingly, their application in quantitative Ab-binding capacity assays combined with high-dimensional profiling of human PBMC enabled the systematic assessment of receptor expression profiles across large numbers of cellular phenotypes. This analysis confirmed increased monocytic Siglec-1 expression in active systemic lupus erythematosus patients and, additionally, revealed interrelated reductions of CD4 expression by regulatory and memory CD4 T cells and HLA-DR expression by myeloid dendritic cells, pointing toward defective cross-talk at the immunological synapse that may limit immune responses in systemic lupus erythematosus. By converting conventional flow cytometry beads into beads suitable for mass cytometry, our approach paves the way toward the broad implementation of bead-based assays in high-dimensional cell profiling studies by mass cytometry in biomedical research.<\/jats:p>","DOI":"10.4049\/jimmunol.1801640","type":"journal-article","created":{"date-parts":[[2019,4,15]],"date-time":"2019-04-15T18:35:24Z","timestamp":1555353324000},"page":"3103-3112","source":"Crossref","is-referenced-by-count":21,"title":["Osmium-Labeled Microspheres for Bead-Based Assays in Mass Cytometry"],"prefix":"10.1093","volume":"202","author":[{"given":"Lisa","family":"Budzinski","sequence":"first","affiliation":[{"name":"German Rheumatism Research Centre Berlin, a Leibniz Institute , 10117 Berlin ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5106-0148","authenticated-orcid":false,"given":"Axel R","family":"Schulz","sequence":"additional","affiliation":[{"name":"German Rheumatism Research Centre Berlin, a Leibniz Institute , 10117 Berlin ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Baumgart","sequence":"additional","affiliation":[{"name":"German Rheumatism Research Centre Berlin, a Leibniz Institute , 10117 Berlin ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tyler","family":"Burns","sequence":"additional","affiliation":[{"name":"German Rheumatism Research Centre Berlin, a Leibniz Institute , 10117 Berlin ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Rose","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Charit\u00e9 University Medicine , 10117 Berlin ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heike","family":"Hirseland","sequence":"additional","affiliation":[{"name":"German Rheumatism Research Centre Berlin, a Leibniz Institute , 10117 Berlin ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik E","family":"Mei","sequence":"additional","affiliation":[{"name":"German Rheumatism Research Centre Berlin, a Leibniz Institute , 10117 Berlin ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,5,15]]},"reference":[{"key":"2025030417562025900_r1","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1111\/j.1749-6632.1993.tb38775.x","article-title":"Fluorescence spectral overlap compensation for any number of flow cytometry parameters","volume":"677","author":"Bagwell","year":"1993","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"2025030417562025900_r2","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1111\/j.1749-6632.1993.tb38760.x","article-title":"Development of clinical standards for flow cytometry","volume":"677","author":"Schwartz","year":"1993","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"2025030417562025900_r3","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1002\/(SICI)1097-0320(19981001)33:2<166::AID-CYTO11>3.0.CO;2-S","article-title":"Flow cytometric quantitation of immunofluorescence intensity: problems and perspectives. European working group on clinical cell analysis","volume":"33","author":"Gratama","year":"1998","journal-title":"Cytometry"},{"key":"2025030417562025900_r4","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1126\/science.905822","article-title":"Quantitative single cell analysis and sorting","volume":"198","author":"Horan","year":"1977","journal-title":"Science"},{"key":"2025030417562025900_r5","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1126\/science.7053559","article-title":"Phagocytosis: flow cytometric quantitation with fluorescent microspheres","volume":"215","author":"Steinkamp","year":"1982","journal-title":"Science"},{"key":"2025030417562025900_r6","doi-asserted-by":"crossref","first-page":"15276","DOI":"10.1021\/ja9052009","article-title":"Lanthanide-containing polymer microspheres by multiple-stage dispersion polymerization for highly multiplexed bioassays","volume":"131","author":"Abdelrahman","year":"2009","journal-title":"J. Am. Chem. Soc."},{"key":"2025030417562025900_r7","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1039\/b921770c","article-title":"Metal-containing polystyrene beads as standards for mass cytometry","volume":"25","author":"Abdelrahman","year":"2010","journal-title":"J. Anal. At. Spectrom."},{"key":"2025030417562025900_r8","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1002\/cyto.a.22271","article-title":"Normalization of mass cytometry data with bead standards","volume":"83","author":"Finck","year":"2013","journal-title":"Cytometry A"},{"key":"2025030417562025900_r9","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1002\/cyto.a.22894","article-title":"OMIP-034: comprehensive immune phenotyping of human peripheral leukocytes by mass cytometry for monitoring immunomodulatory therapies","volume":"91","author":"Baumgart","year":"2017","journal-title":"Cytometry A"},{"key":"2025030417562025900_r10","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1002\/cyto.a.22778","article-title":"Platinum-conjugated antibodies for application in mass cytometry","volume":"89","author":"Mei","year":"2016","journal-title":"Cytometry A"},{"key":"2025030417562025900_r11","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1016\/j.cels.2018.02.010","article-title":"Compensation of signal spillover in suspension and imaging mass cytometry","volume":"6","author":"Chevrier","year":"2018","journal-title":"Cell Syst."},{"key":"2025030417562025900_r12","first-page":"2022","article-title":"Barcoding of live human peripheral blood mononuclear cells for multiplexed mass cytometry","volume-title":"J. Immunol.","author":"Mei","year":"2015"},{"key":"2025030417562025900_r13","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1007\/978-1-4939-2963-4_7","article-title":"Multiparameter phenotyping of human PBMCs using mass cytometry","volume":"1343","author":"Leipold","year":"2015","journal-title":"Methods Mol. Biol."},{"key":"2025030417562025900_r14","author":"Bangs Laboratories Inc","year":"2016"},{"key":"2025030417562025900_r15","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1002\/cyto.a.22904","article-title":"Silver nanoparticles for the detection of cell surface antigens in mass cytometry","volume":"91","author":"Schulz","year":"2017","journal-title":"Cytometry A"},{"key":"2025030417562025900_r16","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1111\/cgf.12893","article-title":"Cytosplore: Interactive immune cell phenotyping for large single-cell datasets","volume":"35","author":"H\u00f6llt","year":"2016","journal-title":"Comput. Graph. Forum"},{"key":"2025030417562025900_r17","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1038\/nbt.2594","article-title":"viSNE enables visualization of high dimensional single-cell data and reveals phenotypic heterogeneity of leukemia","volume":"31","author":"Amir","year":"2013","journal-title":"Nat. Biotechnol."},{"key":"2025030417562025900_r18","doi-asserted-by":"crossref","first-page":"1740","DOI":"10.1038\/s41467-017-01689-9","article-title":"Visual analysis of mass cytometry data by hierarchical stochastic neighbour embedding reveals rare cell types","volume":"8","author":"van Unen","year":"2017","journal-title":"Nat. Commun."},{"key":"2025030417562025900_r19","doi-asserted-by":"crossref","first-page":"748","DOI":"10.12688\/f1000research.11622.1","article-title":"CyTOF workflow: differential discovery in high-throughput high-dimensional cytometry datasets","volume":"6","author":"Nowicka","year":"2017","journal-title":"F1000 Res."},{"key":"2025030417562025900_r20","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1126\/science.1198704","article-title":"Single-cell mass cytometry of differential immune and drug responses across a human hematopoietic continuum","volume":"332","author":"Bendall","year":"2011","journal-title":"Science"},{"key":"2025030417562025900_r21","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1002\/cyto.a.22625","article-title":"FlowSOM: using self-organizing maps for visualization and interpretation of cytometry data","volume":"87","author":"Van Gassen","year":"2015","journal-title":"Cytometry A"},{"key":"2025030417562025900_r22","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1002\/cyto.a.23030","article-title":"Comparison of clustering methods for high-dimensional single-cell flow and mass cytometry data","volume":"89","author":"Weber","year":"2016","journal-title":"Cytometry A"},{"key":"2025030417562025900_r23","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1177\/0961203317722848","article-title":"Effector T-cells are expanded in systemic lupus erythematosus patients with high disease activity and damage indexes","volume":"27","author":"Piantoni","year":"2018","journal-title":"Lupus"},{"key":"2025030417562025900_r24","doi-asserted-by":"crossref","first-page":"2018","DOI":"10.1002\/art.40181","article-title":"Plasmablasts with a mucosal phenotype contribute to plasmacytosis in systemic lupus erythematosus","volume":"69","author":"Mei","year":"2017","journal-title":"Arthritis Rheumatol."},{"key":"2025030417562025900_r25","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1002\/cyto.a.22060","article-title":"Human CD4+ lymphocytes for antigen quantification: characterization using conventional flow cytometry and mass cytometry","volume":"81","author":"Wang","year":"2012","journal-title":"Cytometry A"},{"key":"2025030417562025900_r26","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1186\/1559-0275-11-43","article-title":"Quantifying CD4 receptor protein in two human CD4+ lymphocyte preparations for quantitative flow cytometry","volume":"11","author":"Wang","year":"2014","journal-title":"Clin. Proteomics"},{"key":"2025030417562025900_r27","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1002\/cyto.b.20359","article-title":"Performance of calibration standards for antigen quantitation with flow cytometry in chronic lymphocytic leukemia","volume":"72","author":"Rossmann","year":"2007","journal-title":"Cytometry B Clin. Cytom."},{"key":"2025030417562025900_r28","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1002\/(SICI)1097-0320(19981001)33:2<179::AID-CYTO12>3.0.CO;2-R","article-title":"Quantitative fluorescence flow cytometry: a comparison of the three techniques for direct and indirect immunofluorescence","volume":"33","author":"Serke","year":"1998","journal-title":"Cytometry"},{"key":"2025030417562025900_r29","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1002\/(SICI)1097-0320(19981001)33:2<197::AID-CYTO14>3.0.CO;2-P","article-title":"Determination of CD4 antigen density on cells: role of antibody valency, avidity, clones, and conjugation","volume":"33","author":"Davis","year":"1998","journal-title":"Cytometry"},{"key":"2025030417562025900_r30","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1002\/cyto.a.22848","article-title":"Enhanced multiplexing in mass cytometry using osmium and ruthenium tetroxide species","volume":"89","author":"Catena","year":"2016","journal-title":"Cytometry A"},{"key":"2025030417562025900_r31","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1002\/cyto.a.23000","article-title":"Cell size assays for mass cytometry","volume":"91","author":"Stern","year":"2017","journal-title":"Cytometry A"},{"key":"2025030417562025900_r32","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1002\/pol.1972.150100128","article-title":"Modified osmium tetroxide stain for the microscopy of rubber-toughened resins","volume":"10","author":"Riew","year":"1972","journal-title":"J. Polym. Sci. A-1 Polym. Chem."},{"key":"2025030417562025900_r33","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1002\/pen.760070110","article-title":"The osmium tetroxide procedure for light and electron microscopy of ABS plastics","volume":"7","author":"Kato","year":"1967","journal-title":"Polym. Eng. Sci."},{"key":"2025030417562025900_r34","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1007\/978-1-4684-4613-5_12","volume-title":"Structure-Property Relationships of Polymeric Solids.","author":"Trent","year":"1983"},{"key":"2025030417562025900_r35","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1177\/0961203316640922","article-title":"Autoantibodies, complement and type I interferon as biomarkers for personalized medicine in SLE","volume":"25","author":"Biesen","year":"2016","journal-title":"Lupus"},{"key":"2025030417562025900_r36","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.1136\/annrheumdis-2012-201586","article-title":"IFN\u03b1 and its response proteins, IP-10 and SIGLEC-1, are biomarkers of disease activity in systemic lupus erythematosus","volume":"72","author":"Rose","year":"2013","journal-title":"Ann. Rheum. Dis."},{"key":"2025030417562025900_r37","doi-asserted-by":"crossref","first-page":"1595","DOI":"10.1093\/intimm\/dxh160","article-title":"Phenotypic and functional deficiencies of monocyte-derived dendritic cells in systemic lupus erythematosus (SLE) patients","volume":"16","author":"K\u00f6ller","year":"2004","journal-title":"Int. Immunol."},{"key":"2025030417562025900_r38","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1126\/science.285.5425.221","article-title":"The immunological synapse: a molecular machine controlling T cell activation","volume":"285","author":"Grakoui","year":"1999","journal-title":"Science"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/202\/10\/3103\/61872626\/ji1801640.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/202\/10\/3103\/61872626\/ji1801640.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,4]],"date-time":"2025-03-04T15:08:45Z","timestamp":1741100925000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/202\/10\/3103\/7952123"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,5]]},"references-count":38,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2019,5,15]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.1801640","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2019,5]]},"published":{"date-parts":[[2019,5]]}}}