Pre-B-cell colony-enhancing factor is markedly elevated in childhood hemophagocytic lymphohistiocytosis

Abstract

ABSTRACT. Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening syndrome involving a final common pathway of hypercytokinemia, in which tumor necrosis factor (TNF)-a, interferon (IFN)-g, and soluble interleukin 2-receptor-alpha (sIL-2Ra) are the key cytokines. Pre-B-cell colony-enhancing factor (PBEF) is an inflammatory cytokine involved in several inflammatory diseases. However, its role in HLH is unknown. In this study, we examined the role of PBEF in HLH. Plasma was collected from 22 children with HLH and 14 healthy children. The concentrations of plasma PBEF, TNF-a, IFN-g, and sIL2Ra were determined using an enzyme-linked immunosorbent assay. All clinical data were derived from medical records. In the acute phase, children with HLH had much higher PBEF, TNF-a, IFN-g, and sIL2Ra levels than did healthy children (P < 0.05). After treatment, 13 HLH children improved and PBEF, TNF-a, and IFN-g levels decreased to normal levels (P < 0.05); sIL-2Ra levels also decreased (P < 0.05), but remained above the normal level (P < 0.05). Two patients were lost to follow-up, while 7 patients showed a bad response to therapy and eventually died, showing high PBEF levels above those of the survivors (P < 0.01). PBEF level was significantly positively correlated with TNF-a, IFN-g, sIL-2Ra, serum ferritin, and triglycerides (all P < 0.05), and was negatively correlated with fibrin (P < 0.05). PBEF appears to be involved in the inflammatory process of HLH, and elevated PBEF is related to disease activity. We are currently evaluating the role of PBEF as a marker for the diagnosis and management of patients.

NAMPT serum levels are selectively elevated in acute infectious disease and in acute relapse of chronic inflammatory diseases in children

“…Only few studies analyzed NAMPT in the context of inflammatory processes in childhood [17,18]. We had previously shown, that mainly mono- and granulocytes secrete circulating NAMPT and that mildly elevated leucocytes in obesity may contribute to the phenomenon of slightly increased NAMPT levels in low-grade inflammation in obesity [12].…”

“…There are only few studies focussing on NAMPT in inflammatory states during childhood [17,18]. We have evidence indicating that NAMPT is elevated in childhood obesity and its corresponding low-grade inflammation [12].…”

High soluble interleukin-2 receptor values in Indian paediatric & adult controls – Need for population-specific threshold in the diagnosis of haemophagocytic lymphohistiocytosis

“…However, Japanese controls had a lower serum sIL2R in children and in adults with ages similar to our series 7 . In China, Gao et al 8 too reported low levels of sIL2R in children aged 2-3 yr. Two reports used the same manufacturer as the present study, Zhao et al 9 described serum sIL2R in Chinese children aged 3-12 yr similar to the present study, while Deveci et al 10 reported considerably lower sIL2R than the present study 9 10 ( Table V ). Thus, both children and adults from India seem to have higher serum sIL2R concentrations than most reports.…”

A scopic review on the diagnostic dilemmas and newer treatment modalities in Hemophagocytic Lymphohistiocytosis

“…This has shown a better specificity because with remission it touches the baseline levels, as compared to IL2 receptor levels which stays mildly elevated for some time. 48 Hybrid immunotherapy is a new treatment modality which is being tried in few centers where steroid, etoposide and ATG are being used. Other regimens with the primary agent being alemtuzumab and tocilizumab (IL-6 receptor inhibitor) are being studied in France and Philadelphia respectively.…”