20.500.12556/DiRROS-13806 Somatic mutations and the risk of undifferentiated autoinflammatory disease in MDS : an under-recognized but prognostically important complication 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 somaticmutation 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 inMDS. 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. myelodysplastic syndromes - genetics autoinflammation undifferentiated autoinflammatory disease molecular characterization somatic mutations mielodisplastični sindrom - genetika avtovnetne bolezni nediferencirana avtovnetna bolezen molekularna karakterizacija somatske mutacije true false true Frontiers Media SA Angleški jezik Ni določen © 2021 Watad, Kacar, Bragazzi, Zhou, Jassam, Taylor, Roman, Smith, Jones, Amital, Cargo, McGonagle and Savic Neznano 2021-03-31 14:40:29 2021-03-31 14:40:30 2022-08-19 03:36:51 0000-00-00 00:00:00 2021 0 Švica 0 Nasl. z nasl. zaslona; Soavtor iz Slovenije: Mark Kačar; "Abdulla Watad and Mark Kacar have contributed equally to this work" -> str. 1; Opis vira z dne 30. 3. 2021; Št. prispevka: 610019; str. 1-12 [Vol.] 12 19 Feb. 2021 0000-00-00 Zaloznikova VTisku NiDoloceno 0000-00-00 0000-00-00 0000-00-00 616.1 1664-3224 10.3389/fimmu.2021.610019 57751555 RAZ_Watad_Abdulla_i2021.pdf RAZ_Watad_Abdulla_i2021.pdf 1 63C4C8014615A01BD615F843CEC939C6 2d553baec107eebe6b5e426c95a7ab38ccb8982eeb70bb4b3e595cd047acb990 83c0f062-17b6-11ed-b6b8-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=17139 https://www.frontiersin.org/articles/10.3389/fimmu.2021.610019/pdf 1 https://dirros.openscience.si/Dokument.php?lang=slv&id=16907 Univerzitetna klinika za pljučne bolezni in alergijo Golnik 0 0 0