Circulating S100A8 and S100A9 protein levels in plasma of patients with acquired aplastic anemia and myelodysplastic syndromes

Abstract

The alarmin family members S100A8 and S100A9 are acute phase inflammation proteins, but they also have been proposed as biomarkers in many malignant and non-malignant diseases. In this study, circulating S100A8 and S100A9 homodimers and S100A8/A9 heterodimers in plasma were systematically investigated by ELISA in aplastic anemia (AA) and myelodysplastic syndromes (MDS). Plasma was obtained from 58 severe AA (SAA) and 30 MDS patients, and from 47 age- and sex-matched healthy donors. In 40 out of the 58 AA subjects, S100A protein levels were measured before and 6 months after immunosuppressive therapy (IST). No differences were observed in AA patients at diagnosis compared to healthy controls for circulating S100A homodimers and heterodimers. After therapy, SAA-responders showed significantly increased circulating S100A8. Non-responding patients had significantly higher levels of circulating S100A8/A9 compared to responders and healthy controls, but without variations of S100A8 and S100A9 homodimers. In MDS patients, circulating S100A8 was significantly elevated compared to those of AA and/or healthy controls. By Pearson correlation analysis of protein levels and blood counts, multiple correlations were found. However, as S100A8 and S100A9 are abundantly present in white blood cells and platelets, correlations with blood counts likely mirror the higher number of cells in the blood of some patients. In conclusion, our findings indicate that circulating S100A8 is increased in MDS but not in AA, and that may be useful to distinguish these diseases in the differential diagnosis of bone marrow failure syndromes. Clinicaltrials.gov identifiers: NCT00260689, NCT00604201, NCT01328587, NCT01623167, NCT00001620, NCT00001397.

Keywords: Aplastic anemia; Bone marrow failure; Myelodysplastic syndromes; S100A8; S100A9.

Conflict of interest statement

Conflict of interest

The authors declare no competing financial interests.

Published by Elsevier Ltd.

Figures

Fig. 1.

Circulating levels of S100A proteins in myelodysplastic syndromes (MDS) and severe aplastic anemia (SAA) patients before and after immunosuppressive therapy (IST). Subjects were divided based on hematological improvement in SAA-responders (Resp) or SAA-non responders (NR). (A) Circulating S100A8, S100A9, and S100A8/A9 levels in SAA at diagnosis, MDS patients, and healthy controls (HC). (B) Circulating S100A8, S100A9, and S100A8/A9 levels in SAA patients after 6 months of IST. Plasma levels of S100A8, S100A9, and S100A8/A9 were compared before and after therapy by paired t-test in responders (C) and non-responders (D). (E–G) Correlograms using S100A protein levels and blood counts. Circulating S100A8, S100A9, and S100A8/A9 levels were correlated with hemoglobin level (Hb), white blood cell (WBC), platelet count (Plt), absolute neutrophil count (ANC), absolute lymphocyte count (ALC), absolute monocyte count (AMC), and absolute reticulocyte count (ARC) in MDS patients (E), and SAA before (F) and after (G) therapy. Values range between −1 (red) and +1 (blue). P < 0.05 was considered statistically significant (*). (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)