Immune-mediated thrombocytopenia and IL-6-mediated thrombocytosis observed in idiopathic multicentric Castleman disease
© 2024 British Society for Haematology and John Wiley & Sons Ltd..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:204 |
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| Enthalten in: |
British journal of haematology - 204(2024), 3 vom: 05. März, Seite 921-930 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Rubenstein, Ayelet I [VerfasserIn] |
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| Links: |
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| Themen: |
Cytokines |
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| Anmerkungen: |
Date Completed 14.03.2024 Date Revised 07.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1111/bjh.19279 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM366593544 |
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| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Shyamsundar, Saishravan |e verfasserin |4 aut | |
| 700 | 1 | |a Bustamante, Mateo Sarmiento |e verfasserin |4 aut | |
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| 700 | 1 | |a Milller, Ira D |e verfasserin |4 aut | |
| 700 | 1 | |a Brandstadter, Joshua D |e verfasserin |4 aut | |
| 700 | 1 | |a Mumau, Melanie D |e verfasserin |4 aut | |
| 700 | 1 | |a Fajgenbaum, David C |e verfasserin |4 aut | |
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