Avtor/Urednik		Watad, Abdulla; Kačar, Mark; Bragazzi, Nicola Luigi; Zhou, Qiao; Jassam, Miriam; Taylor, Jan; Roman, Eve; Smith, Alexandra; Jones, Richard A.; Amital, Howard
Naslov		Somatic mutations and the risk of undifferentiated autoinflammatory disease in MDS
Tip		članek
Vol. in št.		, št. [Vol.] 12
Leto izdaje		2021
Obseg		str. 1-12
ISSN		1664-3224 - Frontiers in immunology
Jezik		eng
Abstrakt		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.
Deskriptorji		Myelodysplastic syndromes Mielodisplastični sindrom Genetics Genetika
Proste vsebinske oznake		avtovnetne bolezni nediferencirana avtovnetna bolezen molekularna karakterizacija somatske mutacije autoinflammation undifferentiated autoinflammatory disease molecular characterization somatic mutations