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

Objective, To characterize the association between the TNF alpha-308A allel e and 1) duration of active disease, 2) peripheral blood mononuclear cell ( PBMC) synthesis of tumor necrosis factor alpha (TNF alpha) in vitro, and 3) pathologic calcifications in patients with juvenile dermatomyositis (DM), Methods. The TNF alpha-308 alleles were determined by polymerase chain reac tion in 37 white patients with juvenile DM and in 29 control subjects. Pati ents were grouped according to duration of immunosuppressive therapy: long (greater than or equal to 36 months) or short (<36 months). Unstimulated PB MC were examined by enzyme-linked immunosorbent assay for TNF alpha product ion in vitro. Sixty-five white patients with juvenile DM were examined for pathologic calcifications. Results. TNF alpha-308A was identified in 18 of 37 patients with juvenile D M, in contrast with 5 of 29 controls (P = 0.009). Sixteen of the 18 patient s with juvenile DM who had the TNF alpha-308A allele had a disease course g reater than or equal to 36 months, compared with 6 of 19 patients with TNF alpha-308G (P = 0.001). PBMC from 16 of the 18 juvenile DM patients with TN F alpha-308A synthesized more TNF alpha (median 53 pg/ml) compared with PBM C from 9 of 19 patients with TNF alpha-308G (median 19 pg/ml) (P = 0.007). Nineteen of 22 juvenile DM patients requiring therapy for greater than or e qual to 36 months produced more TNF alpha (median 20.5 pg/ml) in comparison with 6 of 15 juvenile DM patients with a <36-month treatment course (media n TNF alpha 0.0 pg/ml) (P = 0.005). Detectable calcifications were present in 3 of 8 children with juvenile DM who had TNF alpha-308AA, compared with 2 of 21 children with TNF alpha-308AG and 1 of 36 children who had TNF alph a-308GG (P = 0.017). Conclusion. A long course of juvenile DM and the presence of pathologic cal cifications were associated with the TNF alpha-308A allele and with the inc reased production of TNF alpha, which may perpetuate the inflammatory respo nse.