title: TNFalpha-308A allele in juvenile dermatomyositis: association with increased production of tumor necrosis factor alpha, disease duration, and pathologic calcifications.
abstract: OBJECTIVE
  To characterize the association between the TNFalpha-308A allele and 1) duration of active disease, 2) peripheral blood mononuclear cell (PBMC) synthesis of tumor necrosis factor alpha (TNFalpha) in vitro, and 3) pathologic calcifications in patients with juvenile dermatomyositis (DM).
  
  
  METHODS
  The TNFalpha-308 alleles were determined by polymerase chain reaction in 37 white patients with juvenile DM and in 29 control subjects. Patients were grouped according to duration of immunosuppressive therapy: long (> or =36 months) or short (<36 months). Unstimulated PBMC were examined by enzyme-linked immunosorbent assay for TNFalpha production in vitro. Sixty-five white patients with juvenile DM were examined for pathologic calcifications.
  
  
  RESULTS
  TNFalpha-308A was identified in 18 of 37 patients with juvenile DM, in contrast with 5 of 29 controls (P = 0.009). Sixteen of the 18 patients with juvenile DM who had the TNFalpha-308A allele had a disease course > or =36 months, compared with 6 of 19 patients with TNFalpha-308G (P = 0.001). PBMC from 16 of the 18 juvenile DM patients with TNFalpha-308A synthesized more TNFalpha (median 53 pg/ml) compared with PBMC from 9 of 19 patients with TNFalpha-308G (median 19 pg/ml) (P = 0.007). Nineteen of 22 juvenile DM patients requiring therapy for > or =36 months produced more TNFalpha (median 20.5 pg/ml) in comparison with 6 of 15 juvenile DM patients with a <36-month treatment course (median TNFalpha 0.0 pg/ml) (P = 0.005). Detectable calcifications were present in 3 of 8 children with juvenile DM who had TNFalpha-308AA, compared with 2 of 21 children with TNFalpha-308AG and 1 of 36 children who had TNFalpha-308GG (P = 0.017).
  
  
  CONCLUSIONS
  A long course of juvenile DM and the presence of pathologic calcifications were associated with the TNFalpha-308A allele and with the increased production of TNFalpha, which may perpetuate the inflammatory response.
authors.affiliation: The Children's Memorial Medical Center, Northwestern University Medical School, Chicago, Illinois 60614, USA.
authors.forename: L M
authors.initials: LM
authors.lastname: Pachman
authors.forename: M R
authors.initials: MR
authors.lastname: Liotta-Davis
authors.forename: D K
authors.initials: DK
authors.lastname: Hong
authors.forename: T R
authors.initials: TR
authors.lastname: Kinsella
authors.forename: E P
authors.initials: EP
authors.lastname: Mendez
authors.forename: J M
authors.initials: JM
authors.lastname: Kinder
authors.forename: E H
authors.initials: EH
authors.lastname: Chen
mesh_terms: D000483:Alleles; D002648:Child; D002675:Child, Preschool; D003882:Dermatomyositis / Q000188:drug therapy / Q000235:genetics*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000378:metabolism
chemical_list: D007166:Immunosuppressive Agents; D014409:Tumor Necrosis Factor-alpha