Inflammatory profile of lower risk myelodysplastic syndromes.

Topping, J.; Taylor, A.; Nadat, F.; Crouch, S.; Ibbotson, A.; Cermak, J.; Symeonidis, A.; Tatic, A.; Langemeijer, S.; Hellstrom-Lindberg, E.; Culligan, D.; Garelius, HG.; Ashcroft, J.; Nga, E.; Parker, J.; Kolade, S.; McDermott, MF.; De Witte, T.; Bowen, D.; Smith, A.; Cargo, C.; Savic, S.

Inflammatory profile of lower risk myelodysplastic syndromes.

All Authors

Topping, J.

Taylor, A.

Nadat, F.

Crouch, S.

Ibbotson, A.

Cermak, J.

Symeonidis, A.

Tatic, A.

Langemeijer, S.

Hellstrom-Lindberg, E.

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LTHT Author

Nadat, Fatima
Cargo, Catherine
Savic, Sinisa

LTHT Department

Clinical Immunology & Allergy
Haematological Malignancy Diagnostic Service
Leeds Cancer Centre
NIHR Leeds Biomedical Research Centre

Non Medic

Clinical Scientist

Publication Date

2024

Item Type

Journal Article

Abstract

The precise link between inflammation and pathogenesis of myelodysplastic syndrome (MDS) is yet to be fully established. We developed a novel method to measure ASC/NLRP3 protein specks which are specific for the NLRP3 inflammasome only. We combined this with cytokine profiling to characterise various inflammatory markers in a large cohort of patients with lower risk MDS in comparison to healthy controls and patients with defined autoinflammatory disorders (AIDs). The ASC/NLRP3 specks were significantly elevated in MDS patients compared to healthy controls (p < 0.001) and these levels were comparable to those found in patients with AIDs. The distribution of protein specks positive only for ASC was different to ASC/NLRP3 ones suggesting that other ASC-containing inflammasome complexes might be important in the pathogenesis of MDS. Patients with MDS-SLD had the lowest levels of interleukin (IL)-1beta, tumour necrosis factor (TNF), IL-23, IL-33, interferon (IFN) gamma and IFN-alpha2, compared to other diagnostic categories. We also found that inflammatory cytokine TNF was positively associated with MDS progression to a more aggressive form of disease and IL-6 and IL-1beta with time to first red blood cell transfusion. Our study shows that there is value in analysing inflammatory biomarkers in MDS, but their diagnostic and prognostic utility is yet to be fully validated.