TNFalpha-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 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). CONCLUSION: 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.

Is there lead in the suburbs? Risk assessment in Chicago suburban pediatric practices. Pediatric Practice Research Group.

OBJECTIVE: This study was designed to determine: (1) the prevalence of elevated blood lead (BPb) levels (BPb > or = 10 micrograms/dL) in Chicago suburban children attending Pediatric Practice Research Group practices at 12 and 24 months of age, and (2) the efficacy of the Centers for Disease Control and Prevention (CDC) and Illinois lead exposure risk assessment questions. METHODS: Parents bringing their 1- and 2-year-old children for health supervision visits at pediatric practices completed questionnaires. BPb levels were drawn on children. Both questionnaire and an analyzable BPb level were obtained on 1393 subjects (79.2%). RESULTS: Only 2.1% of our sample had a venous BPb level > or = 10 micrograms/dL (0.48 mumol/L); no subjects had a level > or = 30 micrograms/dL (1.45 mumol/L). The CDC risk assessment questions had a sensitivity of .69 and specificity of .70. Due to the low prevalence of elevated BPb levels in this sample, CDC and Illinois screening strategies had high negative predictive values (.99) and low positive predictive values (.05 and .04, respectively). However, some of the subjects with BPb levels > or = 10 micrograms/dL were not at high risk by CDC and Illinois screening questions; 9 of 29 subjects with elevated lead levels (31%) did not respond affirmatively to any CDC risk assessment questions. The question best predicting an elevated BPb was the determination that the house the child lives in was built before 1960 (sensitivity = .83, specificity = .67). This question is not currently included in CDC or Illinois screening strategies. Screening based on the single question "Was your house built before 1960?" would have missed only five (17%) of the children with BPb levels > or = 10 micrograms/dL. Three of these five children were among the 17.1% of 1-year-olds and 26.3% of 2-year-olds in our sample who had moved. CONCLUSIONS: In this sample, children living in houses built before 1960 should be considered at high risk for high-dose lead exposure. Due to the high mobility of our sample, phrasing the question to include lifetime exposure (ie, Has your child ever lived in a house built before 1960?) should also be considered. Selective BPb testing of high-risk children in low-prevalence suburban areas using this question would miss few children with elevated BPb. Useful risk assessment questions in other areas and other populations may differ.