TNFα-308A allele in juvenile dermatomyositis: Association with increased production of tumor necrosis factor α, disease duration, and pathologic calcifications

Lauren M Pachman*, Margaret R. Liotta-Davis, David K. Hong, T. Randall Kinsella, Eduardo P. Mendez, Jennifer M. Kinder, Edwin H. Chen

*Corresponding author for this work

Research output: Contribution to journalArticle

174 Scopus citations

Abstract

Objective. To characterize the association between the TNFα-308A allele and 1) duration of active disease, 2) peripheral blood mononuclear cell (PBMC) synthesis of tumor necrosis factor α (TNFα) in vitro, and 3) pathologic calcifications in patients with juvenile dermatomyositis (DM). Methods. The TNFα-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 (≥36 months) or short (<36 months). Unstimulated PBMC were examined by enzyme-linked immunosorbent assay for TNFα production in vitro. Sixty-five white patients with juvenile DM were examined for pathologic calcifications. Results. TNFα-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 TNFα-308A allele had a disease course ≥36 months, compared with 6 of 19 patients with TNFα-308G (P = 0.001). PBMC from 16 of the 18 juvenile DM patients with TNFα-308A synthesized more TNFα (median 53 pg/ml) compared with PBMC from 9 of 19 patients with TNFα-308G (median 19 pg/ml) (P = 0.007). Nineteen of 22 juvenile DM patients requiring therapy for ≥36 months produced more TNFα (median 20.5 pg/ml) in comparison with 6 of 15 juvenile DM patients with a <36-month treatment course (median TNFα 0.0 pg/ml) (P = 0.005). Detectable calcifications were present in 3 of 8 children with juvenile DM who had TNFα-308AA, compared with 2 of 21 children with TNFα-308AG and 1 of 36 children who had TNFα-308GG (P = 0.017). Conclusion. A long course of juvenile DM and the presence of pathologic calcifications were associated with the TNFα-308A allele and with the increased production of TNFα, which may perpetuate the inflammatory response.

Original languageEnglish (US)
Pages (from-to)2368-2377
Number of pages10
JournalArthritis and rheumatism
Volume43
Issue number10
DOIs
StatePublished - Oct 30 2000

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Pharmacology (medical)

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