THE ROLE OF ABNORMAL KARYOTYPE AND/OR CERTAIN SOMATIC MUTATIONS IN THE RISK OF AUTOINFLAMMATORY/AUTOIMMUNE DISORDERS IN PATIENTS WITH MYELODYSPLASTIC SYNDROME
- Abdulla Watad, Israel
Abstract
Background and Aims
We tested the hypothesis that autoinflammatory disease and non-specific autoinflammatory features were common in myelodysplastic syndrome (MDS) cohorts and we further theorised that MDS with somatic mutations and karyotypic abnormalities were associated with autoinflammation/autoimmune disorders.
Methods
160 MDS patients recruited between 2012-2018 were evaluated for autoinflammation and its link with karyotypes and somatic mutations status. Patients with autoinflammation were classified as well-defined autoinflammatory diseases or undifferentiated “autoinflammatory state”(UAS) (non-specific symptomatology and non-infection related elevated CRP over 10.0 mg/L on 5 consecutive occasions) and were compared in terms of demographic, clinical, laboratory, cytogenetics charts, and outcomes.
Results
The average age was 75.3±11.7 years (median 77 years), with (n=99, 61.9%) male. 78 (48.8%) patients had an autoinflammatory state, were younger (73.4±11.9 years versus 77±11.2 years, borderline significant), and had more frequently arthritis (n=25, 32.1%, versus n=12, 14.6%, p=0.014), arthralgia (n=32, 41.0%, versus n=18, 22.0%, p=0.0108), skin rash (n=22, 28.2%, versus n=10, 12.2%, p=0.0169), pleuritis (16, 20.5%, versus n=3, 3.7%, p=0.0011) and unexplained fever (n=18, 23.1% versus n=0, 0.0%, p<0.0001). 24.4% of autoinflammatory MDS patients had well-defined autoinflammatory disorders (neutrophilic dermatosis, and polymyalgia rheumatic being the commonest). Mutations affecting the transcription factor pathway (NPM1, RUNX1, BCOR, WTI, TP53) (OR 3.22 [95%CI 1.05-9.36], p=0.0402) and deletion of chromosome 5 (OR 3.37 [95%CI 1.01-11.30], p=0.0485) were associated with autoinflammation.
Conclusions
Both well-defined and UAS are common in MDS. Transcription factor pathway somatic mutations and abnormal karyotype are associated with the risk of autoinflammation which is also linked to malignant transformation and worse prognosis.