open access

https://hdl.handle.net/2115/88234

Glycogen synthase kinase 3 beta/CCR6-positive bone marrow cells correlate with disease activity in multicentric Castleman disease-TAFRO

英語

glycogen synthase 3

2022-03

John Wiley & Sons

British journal of haematology

196(5)

1194-1204

Multicentric Castleman disease-thrombocytopenia, anasarca, reticulin fibrosis of bone marrow, renal dysfunction and organomegaly (MCD-TAFRO)-is 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 "chemokine storm", the pathogenesis remains unclear. We aimed to identify pathogenic key molecules, potential diagnostic targets and therapeutic markers in MCD-TAFRO using serum cytokine/chemokine profiles. We performed the targeted cytokine/chemokine multiplex analysis in six cases of MCD-TAFRO with remission or non-remission status. We observed significant changes in serum concentrations of CCL2, CCL5, and Chitinase-3-like-1 in the MCD-TAFRO 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-TAFRO status. More GSK3 beta(+)CCR6(+) cells like megakaryocytes were detected in the bone marrow of patients with MCD-TAFRO than in those with systemic lupus erythematosus, MCD-not otherwise specified or autoimmune haemophagocytic lymphohistiocytosis. The cellularity of GSK3 beta(+)CCR6(+) cells was correlated with disease activity, including thrombocytopenia and anaemia. In conclusion, GSK3 beta and CCR6 of bone marrow cells were potentially involved in the pathogenesis of MCD-TAFRO and may act as diagnostic targets and therapeutic markers.

学術雑誌論文

Accepted Manuscript

Abe, N., Kono, M., Kono, M., Ohnishi, N., Sato, T., Tarumi, M., Yoshimura, M., Sato, T., Karino, K., Shimizu, Y., Fujieda, Y., Kato, M., Hasebe, R., Oku, K., Murakami, M. and Atsumi, T. (2022), Glycogen synthase kinase 3β/CCR6-positive bone marrow cells correlate with disease activity in multicentric Castleman disease-TAFRO. Br J Haematol, 196: 1194-1204,which has been published in final form at 10.1111/bjh.17993. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving (http://olabout.wiley.com/WileyCDA/Section/id-828039.html).

0007-1048