{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T00:36:27Z","timestamp":1773016587203,"version":"3.50.1"},"reference-count":12,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100004897","name":"Pennsylvania Department of Health","doi-asserted-by":"publisher","award":["4100089394"],"award-info":[{"award-number":["4100089394"]}],"id":[{"id":"10.13039\/100004897","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI175771"],"award-info":[{"award-number":["AI175771"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI182319\u201002"],"award-info":[{"award-number":["AI182319\u201002"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HL161847"],"award-info":[{"award-number":["HL161847"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NHLBI R38 HL143615"],"award-info":[{"award-number":["NHLBI R38 HL143615"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NIH R61\/R33DH105594"],"award-info":[{"award-number":["NIH R61\/R33DH105594"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NIH5T32AI1I8684\u201009"],"award-info":[{"award-number":["NIH5T32AI1I8684\u201009"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ACR Open Rheumatology"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Multisystem inflammatory syndrome in children (MIS\u2010C) is a rare hyperinflammatory syndrome that follows SARS\u2010CoV\u20102 infection. Prior plasma proteomic analysis from a 2020 cohort of patients with MIS\u2010C at our center revealed a profile characterized by thrombotic microangiopathy (TMA), macrophage activation syndrome (MAS)\u2010associated proteins, and dysregulated interferon\u2010\u03b3 (IFN\u03b3) responses. However, a limitation of that study was that samples were often acquired after treatment. The objective of this study was to identify plasma proteomic signatures that uniquely define MIS\u2010C versus other viral syndromes unconfounded by treatment effects in an independent cohort.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Plasma proteomics was performed using the Olink Explore HT platform on plasma from patients enrolled at emergency department admission with suspected MIS\u2010C (final diagnoses\n                      <jats:italic>N<\/jats:italic>\n                      = 12 MIS\u2010C,\n                      <jats:italic>N<\/jats:italic>\n                      = 30 other viral syndromes). Plasma autoantibody analysis was performed using a custom microbead\u2010based protein array.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Consistent with findings in the 2020 cohort, TMA\u2010 and MAS\u2010associated proteins were more highly expressed, and there was a higher CXCL9 response to IFN\u03b3 in MIS\u2010C compared to viral infection. In contrast to the 2020 cohort, patients with MIS\u2010C did not have lower expression of the IFN\u03b3 suppressive protein TRIM21. On reanalysis of the 2020 cohort, only patients who received intravenous Ig (IVIg) treatment before sampling had low TRIM21 (also known as Ro52\/SSA). IVIg recipients also had anti\u2010Ro52 autoantibodies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>We have validated several unique features of the plasma proteome of patients with MIS\u2010C first identified in 2020. Discrepant TRIM21 expression in these two cohorts is due to anti\u2010Ro52 autoantibodies in IVIg\u2010treated patients. These data support the use of plasma cytokine profiling to rapidly diagnose MIS\u2010C.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/acr2.70181","type":"journal-article","created":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T06:26:26Z","timestamp":1770013586000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Macrophage Activation Syndrome\u2013Associated Proteins and Enhanced Interferon\u2010\u03b3 Responsiveness in the Plasma Proteome of Patients With Multisystem Inflammatory Syndrome in Children in a Pretreatment Replication Single\u2010Center Cohort"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2304-7739","authenticated-orcid":false,"given":"Sarah","family":"McCuaig","sequence":"first","affiliation":[{"name":"Division of Rheumatology Children's Hospital of Philadelphia  Philadelphia Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cara","family":"Toland","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases Children's Hospital of Philadelphia  Philadelphia Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katharine C.","family":"Konvinse","sequence":"additional","affiliation":[{"name":"Division of Allergy and Immunology, Department of Pediatrics Stanford University School of Medicine  Stanford California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emily","family":"Yang","sequence":"additional","affiliation":[{"name":"Division of Immunology and Rheumatology, Department of Medicine Stanford University School of Medicine  Stanford California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul J.","family":"Utz","sequence":"additional","affiliation":[{"name":"Division of Immunology and Rheumatology, Department of Medicine Stanford University School of Medicine  Stanford California"},{"name":"Institute for Immunity, Transplantation, and Infection, Stanford University  Stanford California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura A.","family":"Vella","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases Children's Hospital of Philadelphia  Philadelphia Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Audrey R.","family":"Odom John","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases Children's Hospital of Philadelphia  Philadelphia Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hamid","family":"Bassiri","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases Children's Hospital of Philadelphia  Philadelphia Pennsylvania"},{"name":"Johnson &amp; Johnson Innovative Medicine  Spring House Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edward M.","family":"Behrens","sequence":"additional","affiliation":[{"name":"Division of Rheumatology Children's Hospital of Philadelphia  Philadelphia Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,2,1]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.42062"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-4642(22)00100-6"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc2307574"},{"issue":"10","key":"e_1_2_6_5_1","first-page":"1174","article-title":"Proteomic signatures of multisystem inflammatory syndrome in children (MIS\u2010C) associated with COVID\u201019: a narrative review","volume":"11","author":"Dourdouna MM","year":"2024","journal-title":"Children (Basel)"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-27544-6"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1101\/2024.01.11.24301110"},{"key":"e_1_2_6_8_1","unstructured":"NevolaK SM GuessJ ForsbergS et al.OlinkAnalyze: facilitate analysis of proteomic data from Olink. 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