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.

Decreased neutrophil levels in bronchopulmonary dysplasia infants

“…As the constitutive proteins of neutrophils, both S100A8 and S100A9 were primarily derived from neutrophils and accounted for approximately 40% of their total proteins. 22 The above results implied that the number of neutrophils in the lung tissue of SD neonatal rats exposed to 85% O 2 might decrease at PND14. S100A8 and S100A9 are indicative indicators, but not specific indicators of the level of neutrophils.…”

Flaming and fanning: The Spectrum of inflammatory influences in myelodysplastic syndromes

“…Multiple components of the marrow environment and of the MDS cell hierarchy itself can contribute to an inflammatory state which can influence MDS emergence, propagation, and evolution. This state is manifested by enrichment of the NLRP3 inflammasome in concurrent MDS and autoimmune disorders [16], the ability of the NLRP3 inflammasome to drive clonal expansion and pyroptosis independent of genotype [34], and increased blood levels of S100A8 and S100 A9 in MDS [36]. Fig.…”

“…ROS may be generated by a few different pathways. In MDS it is thought to be generated from either somatic mutations or the danger-associated molecular proteins (DAMPs) such as S100A8 or S100A9 [36]. DAMPS or alarmins are molecules released by injured cells during pyroptosis which affect the innate immune system via TLR signaling.…”

Aplastic anemia: Etiology, molecular pathogenesis, and emerging concepts

“…Recent efforts have led to promising metrics to distinguish AA from MDS irrespective of CH. Levels of circulating S100A8, a Toll‐like receptor ligand which exerts its proinflammatory effect via tumor necrosis factor receptor‐associated factor (TRAF) and nuclear factor‐κB (NF‐κB)‐related transcription of TNF‐α and IL‐1b, were shown in a recent study to be elevated in patients with MDS, but not those with AA (or healthy controls) . Such a distinction may provide a sensitive diagnostic tool to differentiate the two entities whose treatment varies in most circumstances.…”

“…shown in a recent study to be elevated in patients with MDS, but not those with AA (or healthy controls). 98 Such a distinction may provide a sensitive diagnostic tool to differentiate the two entities whose treatment varies in most circumstances. The presence of CH (even in cases with a large VAF or somatic mutation associated with pathogenic significance in MDS) in a AA patient does not alter therapeutic decision-making in current practice (such as for whom IST would be preferred), but this may in fact change with improved understanding of AA molecular pathogenesis.…”