Somatic mutations and the risk of undifferentiated autoinflammatory disease in MDS : an under-recognized but prognostically important complicationWatad, Abdulla (Avtor) Kačar, Mark (Avtor) Bragazzi, Nicola Luigi (Avtor) Zhou, Qiao (Avtor) Jassam, Miriam (Avtor) Taylor, Jan (Avtor) Roman, Eve (Avtor) Smith, Alexandra (Avtor) Jones, Richard A. (Avtor) Amital, Howard (Avtor) myelodysplastic syndromes - geneticsautoinflammationundifferentiated autoinflammatory diseasemolecular characterizationsomatic mutationsObjectives: 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.Frontiers Media SA20212021-03-31 14:40:29Neznano13806UDK: 616.1ISSN pri članku: 1664-3224DOI: 10.3389/fimmu.2021.610019COBISS_ID: 57751555sl© 2021 Watad, Kacar, Bragazzi, Zhou, Jassam, Taylor, Roman, Smith, Jones, Amital, Cargo, McGonagle and Savic