Pathogenesis of idiopathic multicentric Castleman's disease focusing on T Cells

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K17444
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54020:Connective tissue disease and allergy-related
• Research Institution: Nagasaki University
• Principal Investigator: Sumiyoshi Remi 長崎大学, 病院(医学系), 助教 (70859363)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 特発性多中心性キャッスルマン病 / iMCD-NOS / iMCD-TAFRO / mTOR / IGFBP-1

Outline of Final Research Achievements

Idiopathic multicentric Castleman's disease (iMCD) is a lymphoproliferative disorder characterized by systemic inflammation. We focused on the molecular differences between iMCD-TAFRO, a more severe form of idiopathic multicentric Castleman's disease (iMCD) with TAFRO signs, and iMCD-NOS, another form of iMCD. RNA sequencing using peripheral blood CD4-positive T cells showed that iMCD-TAFRO patients had enhanced mTOR-related signaling compared to iMCD-NOS. IGFBP-1, a serum protein suggested to be associated with the pathogenesis of iMCD, was also examined by ELISA. Serum IGFBP-1 levels were significantly higher in iMCD-TAFRO than in iMCD-NOS. Serum IGFBP-1 is a protein that has been showed to be associated with the mTOR pathway. In this study, the mTOR pathway was shown to be more activated in iMCD-TAFRO compared to iMCD-NOS, which may contribute to differences in pathogenesis and clinical manifestations.

Free Research Field

リウマチ・膠原病内科

Academic Significance and Societal Importance of the Research Achievements

特発性多中心性キャッスルマン病（iMCD）は臨床病型（iMCD-TAFROとiMCD-NOS）によって臨床経過、重症度、治療反応性が異なっており、多様性に富む疾患群である。患者末梢血のCD4陽性T細胞のRNAシーケンスではiMCD-TAFROはiMCD-NOSよりもmTOR関連経路が亢進しており、それと関連する蛋白である血清IGFBP-1も有意に高値であった。これらの違いが病態の違いと関連している可能性があり、臨床病型の差異として現れていることが示唆された。この結果が今後のiMCDの臨床病型毎の治療戦略に役立つことが期待される。