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Published on: May 10, 2017
Soluble TWEAK is markedly elevated in hemophagocytic lymphohistiocytosis
Masayuki Nagasawa1, Zhu Yi, Shinsaku Imashuku
1Department of Pediatrics and Developmental Biology, Postgraduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan. mnagasawa.ped@tmd.ac.jp
Abstract:
Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is a newly identified monocyte derived cytokine, which has weak apoptosis inducing function against sensitive tumor cell lines in vitro. Also, TWEAK has been reported to have proangiogenic and proinflammatory activities in vivo. However, its functions in pathological situation remain to be elucidated. Here, we analyzed soluble TWEAK in serum of 24 patients with hemophagocytic lymphohistiocytosis (HLH) in combination with interferon-gamma (IFN-gamma) and killer-specific secretory protein of 37 kDa (Ksp37). Soluble TWEAK was not detected in serum of healthy individuals. Soluble TWEAK was markedly elevated in all six primary HLH patients and 12 of 18 secondary HLH patients. Serum IFN-gamma, which is an only known mediator to stimulate TWEAK production in monocyte in vitro, was not elevated despite elevated serum TWEAK in three of six primary HLH patients, although IFN-gamma was markedly elevated in other cases. Ksp37 was only slightly increased in HLH patients. These results indicate that TWEAK may be involved in pathogenesis of HLH and is useful as a clinical marker.
Insights
Soluble tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is elevated in hemophagocytic lymphohistiocytosis (HLH) patients, suggesting its role in the disease. This finding highlights TWEAK as a potential clinical marker for HLH diagnosis.
Area of Science:
- Immunology
- Cytokine Biology
- Hematology
Background:
- Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is a cytokine with known proangiogenic and proinflammatory activities.
- Its specific role in pathological conditions like hemophagocytic lymphohistiocytosis (HLH) requires further investigation.
Purpose of the Study:
- To analyze soluble TWEAK levels in patients with hemophagocytic lymphohistiocytosis (HLH).
- To evaluate the potential of soluble TWEAK as a clinical marker for HLH.
Main Methods:
- Serum samples from 24 HLH patients and healthy individuals were analyzed.
- Soluble TWEAK, interferon-gamma (IFN-gamma), and killer-specific secretory protein of 37 kDa (Ksp37) levels were measured.
Main Results:
- Soluble TWEAK was undetectable in healthy individuals but markedly elevated in most HLH patients.
- Elevated serum TWEAK was observed even when IFN-gamma levels were not increased, suggesting TWEAK production may not solely depend on IFN-gamma in HLH.
- Ksp37 levels showed only slight increases in HLH patients.
Conclusions:
- Soluble TWEAK is implicated in the pathogenesis of hemophagocytic lymphohistiocytosis.
- Soluble TWEAK serves as a potential and valuable clinical biomarker for HLH.
