Elevated soluble interleukin-2 receptor in childhood hemophagocytic histiocytic syndromes

Komp, Diane M.; McNamara, James; Buckley, Patrick J.

doi:10.1182/blood.v73.8.2128.bloodjournal7382128

Cited by 105 publications

(74 citation statements)

References 26 publications

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“…Interestingly, in the present study, the degree of spontaneous activation of caspase-3-like enzymes in IL-2-stimulated lymphocytes, as evidenced by the in vitro cleavage of the¯uorogenic substrate DEVD-AMC, was markedly reduced in three of the four FHL patients sampled prior to initiation of etoposide therapy. Previous reports have described decreased proliferative responses to mitogenic stimulation in FHL patients (Ladisch et al, 1978;Egeler et al, 1996). Whether this may in¯uence the subsequent degree of spontaneous caspase activation upon cell culture is presently unknown.…”

Section: Discussionmentioning

confidence: 94%

Induction of apoptosis and caspase activation in cells obtained from familial haemophagocytic lymphohistiocytosis patients

1999

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Summary. Familial haemophagocytic lymphohistiocytosis (FHL) is a rare and uniformly fatal disorder of early childhood characterized by fever, hepatosplenomegaly, cytopenia and widespread in®ltration of vital organs by activated lymphocytes and macrophages. In order to test whether the massive accumulation of immune cells in these patients is associated with a perturbation of apoptosis, lymphocytes were isolated from eight patients and subjected to the chemotherapeutic agent etoposide or agonistic anti-Fas monoclonal antibodies in vitro. These stimuli elicited a normal apoptotic response in FHL patient cells when compared to healthy controls, as determined by phosphatidylserine exposure, DNA fragmentation, in vitro cleavage of the caspase-3-like substrate aspartate-glutamate-valine-aspartate-7-amino-4-methylcoumarin (DEVD-AMC) and proteolysis of the anti-apoptotic protein Bcl-2. In addition, the degree of constitutive and Fastriggered apoptosis in freshly isolated neutrophils was monitored in three children, with similar results. These studies indicate that immune cells derived from FHL patients are not inherently resistant to apoptosis induction. Speci®-cally, etoposide-induced and Fas-triggered activation of intracellular caspases appears to remain intact in these individuals. However, the degree of spontaneous activation of caspase-3-like enzymes in activated lymphocytes was attenuated in three of the four patients tested prior to initiation of therapy, suggesting a possible biological de®ciency in these individuals.

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Section: Discussionmentioning

confidence: 94%

Induction of apoptosis and caspase activation in cells obtained from familial haemophagocytic lymphohistiocytosis patients

1999

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“…Since 1989, serum sIL-2Ra as an indicator of activated CTLs gradually became recognized as an important biomarker for HLH diagnosis, culminating in the HLH-2004 criteria (Komp et al, 1989;Hayden et al, 2016;Lin et al, 2017). Although a few diagnostic guidelines adopted by certain centres exclude the measurement of sIL-2Ra for the diagnosis of HLH, the HLH-2004 guideline is still the most widely cited one (Hayden et al, 2016;Lin et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2020

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Summary Lymphoma‐associated haemophagocytic lymphohistiocytosis (L‐HLH) is characterized by excessively activated macrophages and cytotoxic T lymphocytes, but few reliable markers for activated macrophages are available clinically. This study, designed to discover novel biomarkers for the diagnosis of lymphoma patients with L‐HLH, was initiated between 2016 and 2018. Fifty‐seven adult lymphoma patients were enrolled — 39 without HLH and 18 with HLH. The differential serum protein expression profile was first screened between lymphoma patients with and without L‐HLH by a quantitative mass spectrometric approach. Soluble V‐set and immunoglobulin domain‐containing 4 (sVSIG4), specifically expressed by macrophages, was significantly upregulated in the L‐HLH group. Subsequently, sVSIG4 concentration was confirmed by enzyme‐linked immunosorbent assay to be significantly increased in lymphoma patients with L‐HLH. When it was exploited for the diagnosis of lymphoma patients with L‐HLH, the area under a receiver operating characteristic curve was 0·98 with an optimal cut‐off point of 2195 pg/ml and the corresponding sensitivity and specificity were 94·44% and 94·87% respectively. In addition, the one‐year overall survival was significantly worse in patients with a sVSIG4 concentration above 2195 pg/ml compared with those below 2195 pg/ml (5·3% vs. 72·2%, P < 0·0001). sVSIG4 may be a surrogate marker of activated macrophages for the diagnosis of lymphoma patients with L‐HLH.

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“…Also, M-CSF was found to be elevated in KD [14]. In addition, soluble IL-2 receptor, another parameter particularly typical for HLH [15], was also found to be elevated in KD [15,16]. IL-1-b is normal in HLH [17], but was elevated in at least individual KD patients [18], whereas IFN-g is elevated in HLH [11], but was normal in some patients with KD [12,16].…”

Section: Discussionmentioning

confidence: 99%

Hemophagocytic lymphohistiocytosis and Kawasaki disease: Combined manifestation and differential diagnosis

Titze

Janka

Schneider

et al. 2009

Pediatric Blood & Cancer

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Both hemophagocytic lymphohistiocytosis (HLH) and Kawasaki disease (KD) are diagnosed in patients with prolonged resistant fever by using a scoring system. Concurrent manifestation of both conditions has been reported previously. We describe an infant of 7 weeks whose condition fulfilled the criteria of HLH, but who, after clinical response to treatment, suddenly died from a myocardial infarction at 11 weeks. Post-mortem examination revealed a previously unknown coronary arteritis typical for KD. Since it is difficult to distinguish between KD and HLH, both diseases should be considered in young children with overlapping symptoms. Repeated echocardiograms may be helpful in these cases.

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Elevated soluble interleukin-2 receptor in childhood hemophagocytic histiocytic syndromes

Cited by 105 publications

References 26 publications

Induction of apoptosis and caspase activation in cells obtained from familial haemophagocytic lymphohistiocytosis patients

Induction of apoptosis and caspase activation in cells obtained from familial haemophagocytic lymphohistiocytosis patients

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

Hemophagocytic lymphohistiocytosis and Kawasaki disease: Combined manifestation and differential diagnosis

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