title: Increased plasma thrombospondin-1 (TSP-1) levels are associated with the TNF alpha-308A allele in children with juvenile dermatomyositis.
abstract: Vascular occlusion is more frequent in children with juvenile dermatomyositis (JDM) who have the TNF alpha-308A allele. One of the potent anti-angiogenic factors is thrombospondin-1 (TSP-1). This study investigated the association of the TNF alpha-308A allele with circulating levels of angiogenic mediators, TSP-1, and platelet factor 4 (PF4) using fresh, platelet-poor plasma (PPP). The TNF alpha-308A allele was characterized by PCR amplification and NcoI digestion. Concentrations of TSP-1 and PF4 in PPP from 31 JDM patients and 25 matched pediatric controls were determined by ELISA. The majority of the JDM children with the TNF alpha-308A allele (7/12) produced more TSP-1 than their TNF alpha-308G counterparts (P < 0.05), and their TSP-1 values were inversely related to those for PF4 (P < 0.0006). We conclude that the increased circulating concentrations of TSP-1 associated with the TNF alpha-308A allele suggest that this anti-angiogenic regulator may play a significant role in the augmented vascular occlusion observed in JDM children with this genetic marker.
authors.affiliation: Division of Immunology/Rheumatology, Children's Memorial Hospital, Department of Pediatrics, Northwestern University Medical School, Children's Memorial Institute for Education and Research, Chicago, Illinois 60614, USA.
authors.forename: Jennica
authors.initials: J
authors.lastname: Lutz
authors.forename: Kristin G
authors.initials: KG
authors.lastname: Huwiler
authors.forename: Tamara
authors.initials: T
authors.lastname: Fedczyna
authors.forename: Toula S
authors.initials: TS
authors.lastname: Lechman
authors.forename: Susan
authors.initials: S
authors.lastname: Crawford
authors.forename: T Randell
authors.initials: TR
authors.lastname: Kinsella
authors.forename: Lauren M
authors.initials: LM
authors.lastname: Pachman
mesh_terms: D000483:Alleles; D002648:Child; D004247:DNA / Q000737:chemistry / Q000235:genetics; D003882:Dermatomyositis / Q000097:blood / Q000235:genetics / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D010978:Platelet Factor 4 / Q000032:analysis / Q000096:biosynthesis* / Q000276:immunology; D016133:Polymerase Chain Reaction; D019700:Thrombospondin 1 / Q000096:biosynthesis* / Q000097:blood / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology*
chemical_list: D019700:Thrombospondin 1; D014409:Tumor Necrosis Factor-alpha; D010978:Platelet Factor 4; D004247:DNA