Inflammatory profile of lower risk myelodysplastic syndromes

ImmunAID consortium and EU‐MDS consortium

doi:10.1111/bjh.19530

Inflammatory profile of lower risk myelodysplastic syndromes

ImmunAID consortium and EU‐MDS consortium

Research output: Contribution to journal › Article › peer-review

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)-1β, tumour necrosis factor (TNF), IL-23, IL-33, interferon (IFN) γ and IFN-α2, 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-1β 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.

Original language	English
Number of pages	11
Journal	British Journal of Haematology
Early online date	21 May 2024
DOIs	https://doi.org/10.1111/bjh.19530
Publication status	E-pub ahead of print - 21 May 2024

Bibliographical note

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10.1111/bjh.19530Licence: CC BY

Br J Haematol - 2024 - Topping - Inflammatory profile of lower risk myelodysplastic syndromes
© 2024 The Authors.
Final published version, 1.4 MBLicence: CC BY

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@article{11cf1a2a0af2457da72944703dae2b19,

title = "Inflammatory profile of lower risk myelodysplastic syndromes",

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)-1β, tumour necrosis factor (TNF), IL-23, IL-33, interferon (IFN) γ and IFN-α2, 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-1β 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.",

author = "{ImmunAID consortium and EU‐MDS consortium} and Joanne Topping and Adele Taylor and Fatima Nadat and Simon Crouch and Alice Ibbotson and Jaroslav {\v C}erm{\'a}k and Argiris Symeonidis and Aurelia Tatic and Saskia Langemeijer and Eva Hellstr{\"o}m-Lindberg and Dominic Culligan and Garelius, {Hege Gravdahl} and John Ashcroft and Emma Nga and Jane Parker and Seye Kolade and McDermott, {Michael F} and {De Witte}, Theo and David Bowen and Alexandra Smith and Catherine Cargo and Sinisa Savic",

note = "{\textcopyright} 2024 The Authors. ",

year = "2024",

month = may,

day = "21",

doi = "10.1111/bjh.19530",

language = "English",

journal = "British Journal of Haematology",

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T1 - Inflammatory profile of lower risk myelodysplastic syndromes

AU - ImmunAID consortium and EU‐MDS consortium

AU - Topping, Joanne

AU - Taylor, Adele

AU - Nadat, Fatima

AU - Crouch, Simon

AU - Ibbotson, Alice

AU - Čermák, Jaroslav

AU - Symeonidis, Argiris

AU - Tatic, Aurelia

AU - Langemeijer, Saskia

AU - Hellström-Lindberg, Eva

AU - Culligan, Dominic

AU - Garelius, Hege Gravdahl

AU - Ashcroft, John

AU - Nga, Emma

AU - Parker, Jane

AU - Kolade, Seye

AU - McDermott, Michael F

AU - De Witte, Theo

AU - Bowen, David

AU - Smith, Alexandra

AU - Cargo, Catherine

AU - Savic, Sinisa

PY - 2024/5/21

Y1 - 2024/5/21

N2 - 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)-1β, tumour necrosis factor (TNF), IL-23, IL-33, interferon (IFN) γ and IFN-α2, 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-1β 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.

AB - 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)-1β, tumour necrosis factor (TNF), IL-23, IL-33, interferon (IFN) γ and IFN-α2, 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-1β 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.

U2 - 10.1111/bjh.19530

DO - 10.1111/bjh.19530

M3 - Article

C2 - 38772913

SN - 0007-1048

JO - British Journal of Haematology

JF - British Journal of Haematology

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