title: Elevated plasma levels and platelet-associated expression of the pro-thrombotic and pro-inflammatory protein, TNFSF14 (LIGHT), in sickle cell disease.
abstract: Chronic vascular inflammation and endothelial activation may initiate vaso-occlusion in sickle cell disease (SCD). TNFSF14 (CD258; LIGHT), a recently-identified pro-thrombotic and pro-inflammatory tumour necrosis factor (TNF)-superfamily cytokine, has a potent activating effect on endothelial cells. We evaluated whether TNFSF14 production is altered in SCD and whether platelets contribute to this production. TNFSF14 was measured in platelet-free plasma from healthy-control individuals (CON), steady-state sickle cell anaemia (SCA), SCA on hydroxycarbamide therapy (SCAHC) and haemoglobin SC (HbSC) patients. Mean plasma TNFSF14 was significantly increased in SCA, SCAHC and HbSC, compared to CON individuals. In SCA/SCAHC patients, plasma TNFSF14, showed no correlation with haematological variables, but was significantly correlated with serum lactate dehydrogenase and inflammatory markers (CD40LG , IL8 and ICAM1). Platelet-membrane TNFSF14 expression was significantly augmented on SCA platelets, and correlated with platelet activation; furthermore, measurement of platelet TNFSF14 release indicated that platelets may be a major source of circulating TNFSF14 in SCA. Interestingly, high plasma TNFSF14 was significantly associated with elevated tricuspid regurgitant velocity (≥2·5 m/s) in a population of SCA/SCAHC patients. The pro-inflammatory and atherogenic cytokine, TNFSF14, could contribute to endothelial activation and inflammation in SCA; future investigations may confirm whether this protein contributes to major clinical complications of the disease, such as pulmonary hypertension, and represents a potential therapeutic target.
authors: INCT de Sangue, Haematology and Haemotherapy Centre, School of Medicine, University of Campinas -UNICAMP, Campinas, SP, Brazil.
authors: Vanessa T
authors: VT
authors: Garrido
authors: Renata
authors: R
authors: Proença-Ferreira
authors: Venina M
authors: VM
authors: Dominical
authors: Fabiola
authors: F
authors: Traina
authors: Marcos A C
authors: MA
authors: Bezerra
authors: Mariana R B
authors: MR
authors: de Mello
authors: Marina P
authors: MP
authors: Colella
authors: Aderson S
authors: AS
authors: Araújo
authors: Sara T O
authors: ST
authors: Saad
authors: Fernando F
authors: FF
authors: Costa
authors: Nicola
authors: N
authors: Conran
mesh_terms: D000293:Adolescent; D000328:Adult; D000755:Anemia, Sickle Cell / Q000097:blood* / Q000150:complications / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D015415:Biomarkers; D001792:Blood Platelets / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000473:pathology; D005260:Female; D005838:Genotype; D006444:Hemoglobin C / Q000235:genetics; D006445:Hemoglobin C Disease / Q000097:blood / Q000235:genetics; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use; D018836:Inflammation Mediators / Q000097:blood; D008297:Male; D008875:Middle Aged; D015539:Platelet Activation; D053240:Receptors, Tumor Necrosis Factor, Member 14 / Q000097:blood; D012805:Sickle Cell Trait / Q000097:blood / Q000235:genetics; D019851:Thrombophilia / Q000209:etiology / Q000378:metabolism; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14 / Q000097:blood* / Q000235:genetics / Q000502:physiology; D055815:Young Adult
chemical_list: D015415:Biomarkers; D018836:Inflammation Mediators; D053240:Receptors, Tumor Necrosis Factor, Member 14; C506028:TNFRSF14 protein, human; C505914:TNFSF14 protein, human; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14; D006444:Hemoglobin C; D006918:Hydroxyurea