Early diagnostic and prognostic significance of a specific Th1/Th2 cytokine pattern in children with haemophagocytic syndrome

Abstract

Summary The haemophagocytic syndrome (HPS) is a rare but frequently fatal disorder of immune regulation caused by hypercytokinemia. Using cytometric bead array technique, the serum T‐helper cell type 1 (Th1) and 2 (Th2) cytokines including interferon‐γ (IFN‐γ), tumour necrosis factor (TNF), interleukin (IL)‐10, IL‐6, IL‐4 and IL‐2 were determined in 24 children with de novo HPS and 87 children as control. The median levels of serum IFN‐γ, IL‐10 and IL‐6 in the acute phase of HPS were 901·7, 879·0 and 63·8 pg/ml, respectively, significantly higher than those after remission, and in the healthy volunteers and patients with viral infection. IL‐4 was slightly elevated while IL‐2 and TNF were within normal range in acute phase. Patients with bacterial sepsis showed an extremely high level of IL‐6 and moderate level of IL‐10, whereas IFN‐γ was only slightly elevated. Five patients were diagnosed with HPS according to the Th1/Th2 cytokine pattern 3–13 d earlier than they fulfilled the relevant diagnostic criteria. IL‐10 level >2000 pg/ml was an unfavorable prognostic factor for HPS treatment response (P = 0·033) and outcome (P = 0·009). We conclude that the significant increase of IFN‐γ and IL‐10 and a slightly increased level of IL‐6 is an early, specific and prognostic cytokine pattern for childhood HPS.

Cytokine release syndrome after blinatumomab treatment related to abnormal macrophage activation and ameliorated with cytokine-directed therapy

“…A cytokine panel obtained 4 days after blinatumomab and 1 day prior to tocilizumab included elevated IL-10 (5338 pg/mL), IL-6 (681 pg/mL), INF-g (192 pg/mL), and IL-2R (4872 pg/mL), helping to confirm the diagnosis of HLH/MAS (Figure 2). 7,8,14,15 After tocilizumab, his cytokines dramatically improved. PRF1, STX1, STXBP2, and MUNC13-4 mutation testing was normal.…”

“…6 These 3 cytokines are also markedly elevated in children with hemophagocytic lymphohistiocytosis (HLH), also known as macrophage activation syndrome (MAS). 7,8 Several patients receiving CD19-specific chimeric antigen receptor-modified T cells (CART-19) have developed cytokine release syndrome (CRS), also marked by elevated IL-6, IL-10, and INF-g. 9 CART-19 is effective in chronic lymphocytic leukemia 10 and is being studied in pediatric B-ALL (NCT01626495). Our group observed that children with B-ALL receiving CART-19 develop CRS with clinical HLH/MAS.…”

How I treat hemophagocytic lymphohistiocytosis

“…Systemic inflammatory processes (such as sepsis) do not tend to display the specific constellation of immunopathologies and/or evidence of T-cell activation, as seen in HLH. 14 Furthermore, whereas rising neutrophil counts, platelet counts, and ‡Although the HLH-2004 protocol uses ferritin Ͼ 500 ng/mL, we generally view ferritin Ͼ 3000 ng/mL as concerning for HLH and ferritin Ͼ 10 000 as highly suspicious. 8 §Elevations above age-adjusted, laboratory-specific normal levels (defined as Ͼ 2 SD from the mean) appear more meaningful than the original designation of Ͼ 2400 U/mL because of variations between laboratories.…”

The Th1/Th2/Th17 cytokine profile of HIV-infected individuals: A multivariate cytokinomics approach

“…Measuring cytokine alterations during HIV infection [11][12][13][14][15][16] and other pathological states [17][18][19][20][21] is increasingly being investigated for use in predicting disease progression.…”