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.

Center of Hematology and Bone Marrow Transplantation Fundeni Clinical Institute Bucharest Romania

Department of Clinical Hematology Institute of Hematology and Blood Transfusion Praha Czech Republic

Department of Clinical Immunology and Allergy St James's University Hospital Leeds UK

Department of Haematology Aberdeen Royal Infirmary Aberdeen UK

Department of Haematology Blackpool Victoria Hospital Blackpool Lancashire UK

Department of Haematology Royal Blackburn Teaching Hospital Blackburn Lancashire UK

Department of Hematology Mid Yorkshire Hospitals Wakefield UK

Department of Hematology Radboud University Medical Center Nijmegen The Netherlands

Department of Specialist Medicine Sahlgrenska University Hospital Göteborg Sweden

Department of Tumor Immunology Nijmegen Center for Molecular Life Sciences Radboud University Medical Center Nijmegen The Netherlands

Division of Hematology Department of Internal Medicine University of Patras Medical School Patras Greece

Division of Hematology Department of Medicine Karolinska Institutet Stockholm Sweden

Epidemiology and Cancer Statistics Group University of York York UK

Haematological Malignancy Diagnostic Service St James's University Hospital Leeds UK

Leeds Institute of Rheumatic and Musculoskeletal Medicine University of Leeds Leeds UK

National Institute for Health Research Leeds Biomedical Research Centre Leeds UK

Northampton General Hospital Northampton UK

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Infections in lower-risk myelodysplastic syndromes - prevalence and risk factors: a report from the European MDS Registry