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- Title
Immune‐mediated thrombocytopenia and IL‐6‐mediated thrombocytosis observed in idiopathic multicentric Castleman disease.
- Authors
Rubenstein, Ayelet I.; Pierson, Sheila K.; Shyamsundar, Saishravan; Bustamante, Mateo Sarmiento; Gonzalez, Michael V.; Milller, Ira D.; Brandstadter, Joshua D.; Mumau, Melanie D.; Fajgenbaum, David C.
- Abstract
Summary: Idiopathic multicentric Castleman disease (iMCD) is a rare haematological disorder characterized by generalized lymphadenopathy with atypical histopathological features and systemic inflammation caused by a cytokine storm involving interleukin‐6 (IL‐6). Three clinical subtypes are recognized: thrombocytopenia, anasarca, fever, renal dysfunction, organomegaly (iMCD‐TAFRO); idiopathic plasmacytic lymphadenopathy (iMCD‐IPL), involving thrombocytosis and hypergammaglobulinaemia; and iMCD‐not otherwise specified (iMCD‐NOS), which includes patients who do not meet criteria for the other subtypes. Disease pathogenesis is poorly understood, with potential involvement of infectious, clonal and/or autoimmune mechanisms. To better characterize iMCD clinicopathology and gain mechanistic insights into iMCD, we analysed complete blood counts, other clinical laboratory values and blood smear morphology among 63 iMCD patients grouped by clinical subtype. Patients with iMCD‐TAFRO had large platelets, clinical severity associated with lower platelet counts and transfusion‐resistant thrombocytopenia, similar to what is observed with immune‐mediated destruction of platelets in immune thrombocytopenic purpura. Conversely, elevated platelet counts in iMCD‐IPL were associated with elevated IL‐6 and declined following anti‐IL‐6 therapy. Our data suggest that autoimmune mechanisms contribute to the thrombocytopenia in at least a portion of iMCD‐TAFRO patients whereas IL‐6 drives thrombocytosis in iMCD‐IPL, and these mechanisms likely contribute to disease pathogenesis.
- Subjects
THROMBOPOIETIN receptors; CASTLEMAN'S disease; THROMBOCYTOSIS; BLOOD cell count; PLATELET count; IDIOPATHIC thrombocytopenic purpura; THROMBOCYTOPENIA; CYTOKINE release syndrome
- Publication
British Journal of Haematology, 2024, Vol 204, Issue 3, p921
- ISSN
0007-1048
- Publication type
Article
- DOI
10.1111/bjh.19279