{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T21:48:10Z","timestamp":1790200090651,"version":"4.1.0"},"reference-count":30,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2021,12,6]],"date-time":"2021-12-06T00:00:00Z","timestamp":1638748800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Multicentric Castleman disease\u2013thrombocytopenia, anasarca, reticulin fibrosis of bone marrow, renal dysfunction and organomegaly (MCD\u2010TAFRO)\u2014is an emergent phenotype characterized by lymphoproliferation, fluid collection, hemocytopenia and multiple organopathy. Although studies have demonstrated an aberrant blood cytokine\/chemokine profile referred to as \u201cchemokine storm\u201d, the pathogenesis remains unclear. We aimed to identify pathogenic key molecules, potential diagnostic targets and therapeutic markers in MCD\u2010TAFRO using serum cytokine\/chemokine profiles. We performed the targeted cytokine\/chemokine multiplex analysis in six cases of MCD\u2010TAFRO with remission or non\u2010remission status. We observed significant changes in serum concentrations of CCL2, CCL5, and Chitinase\u20103\u2010like\u20101 in the MCD\u2010TAFRO patients with active state compared to inactive state. Ingenuity pathway analysis revealed that glycogen synthase kinase 3 (GSK3) and CCR6, which is expressed in megakaryocytes, were detected as upstream positive regulators for activating MCD\u2010TAFRO status. More GSK3\u03b2<jats:sup>+<\/jats:sup>CCR6<jats:sup>+<\/jats:sup> cells like megakaryocytes were detected in the bone marrow of patients with MCD\u2010TAFRO than in those with systemic lupus erythematosus, MCD\u2010not otherwise specified or autoimmune haemophagocytic lymphohistiocytosis. The cellularity of GSK3\u03b2<jats:sup>+<\/jats:sup>CCR6<jats:sup>+<\/jats:sup> cells was correlated with disease activity, including thrombocytopenia and anaemia. In conclusion, GSK3\u03b2 and CCR6 of bone marrow cells were potentially involved in the pathogenesis of MCD\u2010TAFRO and may act as diagnostic targets and therapeutic markers.<\/jats:p>","DOI":"10.1111\/bjh.17993","type":"journal-article","created":{"date-parts":[[2021,12,7]],"date-time":"2021-12-07T02:00:00Z","timestamp":1638842400000},"page":"1194-1204","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Glycogen synthase kinase 3\u03b2\/CCR6\u2010positive bone marrow cells correlate with disease activity in multicentric Castleman disease\u2010TAFRO"],"prefix":"10.1111","volume":"196","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8644-1007","authenticated-orcid":false,"given":"Nobuya","family":"Abe","sequence":"first","affiliation":[{"name":"Department of Rheumatology, Endocrinology and Nephrology Faculty of Medicine and Graduate School of Medicine Hokkaido University Sapporo Japan"},{"name":"Division of Molecular Psychoimmunology Institute for Genetic Medicine Graduate School of Medicine Hokkaido University Sapporo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7663-534X","authenticated-orcid":false,"given":"Michihito","family":"Kono","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Endocrinology and Nephrology Faculty of Medicine and Graduate School of Medicine Hokkaido University Sapporo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michihiro","family":"Kono","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Endocrinology and Nephrology Faculty of Medicine and Graduate School of Medicine Hokkaido University Sapporo Japan"},{"name":"Third Department of Internal Medicine Hokkaido P.W.F.A.C. 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