Somatic Mutations and the Risk of Undifferentiated Autoinflammatory Disease in MDS: An Under-Recognized but Prognostically Important Complication

TY - JOUR

T1 - Somatic Mutations and the Risk of Undifferentiated Autoinflammatory Disease in MDS

T2 - An Under-Recognized but Prognostically Important Complication

AU - Watad, Abdulla

AU - Kacar, Mark

AU - Bragazzi, Nicola Luigi

AU - Zhou, Qiao

AU - Jassam, Miriam

AU - Taylor, Jan

AU - Roman, Eve

AU - Smith, Alexandra

AU - Jones, Richard A

AU - Amital, Howard

AU - Cargo, Catherine

AU - McGonagle, Dennis

AU - Savic, Sinisa

N1 - © 2021 Watad, Kacar, Bragazzi, Zhou, Jassam, Taylor, Roman, Smith, Jones, Amital, Cargo, McGonagle and Savic.

PY - 2021/2/19

Y1 - 2021/2/19

N2 - 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.

AB - 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.

KW - Adolescent

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Alleles

KW - Autoantibodies/immunology

KW - Autoimmunity/genetics

KW - Child

KW - Chromosome Aberrations

KW - Female

KW - Genetic Association Studies

KW - Genetic Predisposition to Disease

KW - Hereditary Autoinflammatory Diseases/diagnosis

KW - Humans

KW - Karyotype

KW - Male

KW - Middle Aged

KW - Mutation

KW - Myelodysplastic Syndromes/complications

KW - Prognosis

KW - Risk Assessment

KW - Risk Factors

KW - Young Adult

U2 - 10.3389/fimmu.2021.610019

DO - 10.3389/fimmu.2021.610019

M3 - Article

C2 - 33679746

SN - 1664-3224

VL - 12

SP - 610019

JO - Frontiers in immunology

JF - Frontiers in immunology

M1 - 610019

ER -