Inflammatory profile of lower risk myelodysplastic syndromes

• Published in: British journal of haematology Vol. 205; no. 3; pp. 1044 - 1054
• Main Authors: Topping, Joanne, Taylor, Adele, Nadat, Fatima, Crouch, Simon, Ibbotson, Alice, Čermák, Jaroslav, Symeonidis, Argiris, Tatic, Aurelia, Langemeijer, Saskia, Hellström‐Lindberg, Eva, Culligan, Dominic, Garelius, Hege Gravdahl, Ashcroft, John, Nga, Emma, Parker, Jane, Kolade, Seye, McDermott, Michael F., De Witte, Theo, Bowen, David, Smith, Alexandra, Cargo, Catherine, Savic, Sinisa
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.09.2024
• Subjects: Blood transfusion; Cytokines; Erythrocytes; Inflammasomes; inflammation; Inflammatory diseases; Interferon; MDS; Medicin och hälsovetenskap; Myelodysplastic syndrome; NLRP3 inflammasome; Pathogenesis; Tumor necrosis factor; Tumor necrosis factor-TNF; cytokines; NLRP3 inflammasome; inflammation; MDS
• ISSN: 0007-1048; 1365-2141; 1365-2141
• DOI: 10.1111/bjh.19530

Summary 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. The pathogenesis of myelodysplastic syndrome (MDS) has been linked to dysregulated inflammation and activation of the NLRP3 inflammasome. The inflammasome activation, as measured by the levels of ASC/NLRP3 specks in the patient sera, is significantly higher in MDS patients compared to healthy controls (HC) and is comparable to patients with prototypic autoinflammatory disorders. The levels of various proinflammatory cytokines such as IL‐18, IL‐6 and IL‐8 are also significantly elevated in MDS patients compared to the healthy controls. Furthermore, TNF is positively associated with MDS progression to a more aggressive forms of disease and IL‐6 and IL‐1b with time to first red blood cell transfusion.