Plasma Levels of Presepsin (Soluble CD14-subtype) as a Novel Prognostic Marker for Hemophagocytic Syndrome in Hematological Malignancies

Abstract

Objective Recent studies suggest that presepsin (soluble CD14-subtype) is a useful diagnostic and prognostic marker for sepsis, with secretion by activated macrophages potentially dependent on phagocytosis of microorganisms. As hemophagocytosis is one of the major characteristics in patients with hemophagocytic syndrome (HPS), we hypothesized that presepsin may reflect the phagocytic activity and be a useful prognostic marker for HPS. Therefore, we aimed to assess the prognostic potential of presepsin in secondary HPS in adult patients with hematological malignancies. Methods Between April 2006 and August 2014, we retrospectively examined consecutive patients with HPS whose blood samples were available at our institution and compared the prognostic value of the following in HPS, singly and in combination: plasma presepsin, serum soluble interleukin (IL)-2 receptor (sIL-2R), ferritin, tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), IL-6 and IL-10. Results A total of 14 patients were enrolled. The median age of the patients was 46.5 years (range, 22-65). In univariable Cox models, there were no significant variables associated with the prognosis. However, in 12 evaluable patients, only the combination of higher median values of presepsin (>1,935 pg/mL) and sIL-2R (>4,585 U/mL) at the onset of HPS was significantly associated with the 90-day mortality (hazard ratio 14.5; 95% CI, 1.47-143.36; p=0.02). Conclusion These results suggest that a composite model of plasma presepsin and serum sIL-2R levels at the onset of HPS might be a novel predictor of the prognosis of patients with hematological malignancies and secondary HPS.

Prognostic value of presepsin in adult patients with sepsis: Systematic review and meta-analysis

“…Presepsin also has been shown to have prognostic value for situations other than sepsis such as cardiac surgery [ 35 ], hemophagocytic syndrome [ 36 ], or renal failure [ 37 ]. In particular, presepsin levels depend on renal function due to a 13-kDa small protein being filtered by the kidney [ 8 , 38 ].…”

Serum soluble VSIG4 as a surrogate marker for the diagnosis of lymphoma‐associated hemophagocytic lymphohistiocytosis

“…Overall, 89 upregulated and 37 downregulated proteins were identified in L-HLH group compared with the non-HLH group (Table II). Among these soluble proteins upregulated in the serum, CD14, CD163, b2-microglobulin, and C-reactive protein (CRP) had been revealed to be present at higher levels in patients with HLH in previous studies (Bleesing et al, 2007;Nanno et al, 2016;Tamamyan et al, 2016;Koh et al, 2017;Machowicz et al, 2017). In addition to CD14 and CD163, other transmembrane proteins expressed on the macrophage's surface were also shown to be significantly upregulated in the serum of L-HLH, such as Fc gamma receptor III-A (FccRIIIA), scavenger receptor MARCO, CSF1 receptor (CSF1R) and VSIG4.…”

Diagnostic usefulness of plasma presepsin (soluble CD14-subtype) for diagnosing hemophagocytic syndrome in hematological malignancies

“…Increasing evidence indicates that presepsin is useful as a diagnostic and prognostic marker for sepsis [8]. Recent reports suggest that blood levels of presepsin are elevated in patients with HPS, and these alterations might be useful for predicting the prognosis of HPS [9,10]. However, to our knowledge, our study is the first to evaluate the diagnostic value of presepsin for HPS.…”

“…Recently, Arai et al showed that human monocytes secrete presepsin in response to a sterile phagocytic stimulus, as well as bacterial phagocytosis, and that serum levels of presepsin in patients with HPS were significantly higher than those in subjects without HPS [9]. Nanno et al found that a composite model of plasma presepsin and serum sIL-2R levels might serve as a useful prognostic marker for HPS [10]. Based on these observations, we hypothesized that presepsin could be a superior diagnostic biomarker, and undertook a cross-sectional study in which we compared the diagnostic performance of plasma presepsin with that of serum ferritin, sIL-2R, IFN-γ, IL-10, and IL-6.…”

“…Between April 2006 and August 2014, we consecutively examined patients whose blood samples at onset of HPS were available in our institution. We diagnosed HPS using the modified HLH-2004 criteria, as previously reported [10,11]. Control blood samples were from patients who had serum ferritin levels of ≥500 µg/L at the onset of febrile neutropenia (FN), and were obtained from subjects who had been enrolled in two previous clinical studies [12,13].…”