Watad, A, Kacar, M, Bragazzi, NL et al. (10 more authors) (2021) Somatic Mutations and the Risk of Undifferentiated Autoinflammatory Disease in MDS: An Under-Recognized but Prognostically Important Complication. Frontiers in Immunology, 12. p. 610019. ISSN 1664-3224
Abstract
Objectives: We theorized that myelodysplastic syndrome (MDS) with somatic mutations and karyotype abnormalities are associated with autoinflammation, and that the presence of autoinflammatory disease affected prognosis in MDS.
Methods: One hundred thirty-four MDS patients were assessed for the prevalence of autoinflammatory complications and its link with karyotypes and somatic mutation status. Autoinflammatory complications were described either as well-defined autoinflammatory diseases (AD) or undifferentiated “autoinflammatory disease” (UAD) (defined as CRP over 10.0 mg/L on five consecutive occasions, taken at separate times and not explained by infection). Several patient characteristics including demographic, clinical, laboratory, cytogenetics charts, and outcomes, were compared between different groups.
Results: Sixty-two (46.3%) patients had an autoinflammatory complication manifesting as arthralgia (43.5% vs. 23.6%, p = 0.0146), arthritis (30.6% vs. 15.3%, p = 0.0340), skin rash (27.4% vs. 12.5%, p = 0.0301), pleuritis (14.5% vs. 4.2%, p = 0.0371) and unexplained fever (27.4% vs. 0%, p < 0.0001). AD were found in 7.4% of MDS patients (with polymyalgia rheumatic being the most frequently one). Classical autoimmune diseases were found only in 4 MDS patients (3.0%). Transcription factor pathway mutations (RUNX1, BCOR, WTI, TP53) (OR 2.20 [95%CI 1.02–4.75], p = 0.0451) and abnormal karyotypes (OR 2.76 [95%CI 1.22–6.26], p = 0.0153) were associated with autoinflammatory complications. Acute leukaemic transformation was more frequent in MDS patients with autoinflammatory features than those without (27.4% vs. 9.7%, p = 0.0080).
Conclusions: Autoinflammatory complications are common in MDS. Somatic mutations of transcription factor pathways and abnormal karyotypes are associated with greater risk of autoinflammatory complications, which are themselves linked to malignant transformation and a worse prognosis.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2021 Watad, Kacar, Bragazzi, Zhou, Jassam, Taylor, Roman, Smith, Jones, Amital, Cargo, McGonagle and Savic. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publicationin this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
Keywords: | myelodysplatic syndrome, autoinflammation, molecular characterization, somatic mutations, undifferentiated autoinflammatory disease |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Institute of Rheumatology & Musculoskeletal Medicine (LIRMM) (Leeds) > Inflammatory Arthritis (Leeds) |
Funding Information: | Funder Grant number Swedish Orphan Biovitrum Ltd 170714 |
Depositing User: | Symplectic Publications |
Date Deposited: | 16 Mar 2021 16:47 |
Last Modified: | 16 Mar 2021 16:47 |
Status: | Published |
Publisher: | Frontiers Media |
Identification Number: | 10.3389/fimmu.2021.610019 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:172169 |