title: Soluble TWEAK is markedly elevated in hemophagocytic lymphohistiocytosis.
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.
authors.affiliation: Department of Pediatrics and Developmental Biology, Postgraduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan. mnagasawa.ped@tmd.ac.jp
authors.forename: Masayuki
authors.initials: M
authors.lastname: Nagasawa
authors.forename: Zhu
authors.initials: Z
authors.lastname: Yi
authors.forename: Shinsaku
authors.initials: S
authors.lastname: Imashuku
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Nonoyama
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Ogawa
authors.forename: Ko
authors.initials: K
authors.lastname: Okumura
authors.forename: Shuki
authors.initials: S
authors.lastname: Mizutani
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000097:blood; D002648:Child; D002675:Child, Preschool; D000074049:Cytokine TWEAK; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D051359:Lymphohistiocytosis, Hemophagocytic / Q000097:blood*; D008297:Male; D048069:Tumor Necrosis Factors / Q000097:blood*
chemical_list: D015415:Biomarkers; D000074049:Cytokine TWEAK; C109743:TNFSF12 protein, human; D048069:Tumor Necrosis Factors