VIDAS3® TB-IGRA assay: evaluation of performance characteristics in a predominantly low risk, low incidence population.

OBJECTIVES: To evaluate the analytical performance of the TB-IGRA® assay on the VIDAS3 platform (bioMérieux) when testing a predominantly low risk population in a low incidence area. RESULTS: Eighty-eight percent of the results were concordant between QuantiFERON®-TB Gold-Plus (QFT®-Plus, QIAGEN) and TB-IGRA®. All 12 of 99 (12.1%) discordant results were determined positive only with the TB-IGRA® assay. In 11 of 12 of these discordant cases, no explanation could be found in the medical record. Five of these discrepant results were probably caused by the use of contaminated stimulation reagents. The remaining 6 discrepant samples were also part of the reproducibility experiment and only 2 results were reproducible positive. Overall, in the reproducibility experiment 5 of 25 (20.0 %) results were not repeatable. CONCLUSIONS: the TB-IGRA® assay seems prone to contamination. Besides, we documented a reproducibility of only 80.0% with the TB-IGRA® assay.

Oxidized low-density lipoprotein, iron stores, and haptoglobin polymorphism.

BACKGROUND: In vitro experimental studies demonstrated that iron promotes free radical-induced low-density lipoprotein (LDL) oxidation. OBJECTIVE: To test the hypothesis that circulating oxidized LDL (oxLDL) levels might be associated with body iron stores (serum ferritin) and iron-related genetic markers (hemochromatosis gene C282Y mutation, haptoglobin polymorphism). METHODS: We investigated 381 (176 males, 205 females, age 45 +/- 6 years) healthy Caucasians. Serum oxLDL, assayed by a mAb-4E6-based enzyme-linked immunosorbent assay (ELISA), was expressed as oxLDL/LDL ratio to adjust for serum LDL-cholesterol concentration. Hemochromatosis gene C282Y mutation analysis was performed by a Taqman-based polymerase chain reaction (PCR) assay. Haptoglobin (Hp) phenotypes (Hp 1-1, Hp 2-1, Hp 2-2) were determined by starch gel electrophoresis. RESULTS: In stepwise multivariate regression analysis, gender (P < 0.0001), current smoking (P < 0.0001), HDL-cholesterol (P = 0.0001), ferritin (P = 0.0051), body mass index (BMI) (P = 0.0063), and Hp phenotype (P = 0.0331) independently predicted oxLDL/LDL ratio in the total group. In men, smoking (P < 0.0001), ferritin (P = 0.0052), Hp phenotype (P = 0.0063), and HDL-cholesterol (P = 0.0127) were independent determinants of oxLDL/LDL ratio. In women, only body mass index (P < 0.0001), HDL-cholesterol (P = 0.0005), and smoking (P = 0.0025) were significantly associated with oxLDL/LDL ratio. The C282Y mutation (wild-type versus C282Y heterozygotes) was not associated with oxLDL/LDL ratio in both sexes. CONCLUSION: Serum ferritin concentration and Hp polymorphism are independently associated with circulating oxLDL levels in males.

Neuronal migration depends on intact peroxisomal function in brain and in extraneuronal tissues.

Functional peroxisome deficiency, as encountered in Zellweger syndrome, causes a specific impairment of neuronal migration. Although the molecular mechanisms underlying the neuronal migration defect are at present unknown, the excess of very long chain fatty acids in brain, a consequence of peroxisomalbeta-oxidation deficiency, has often been hypothesized to play a major role. The purpose of the present study was to investigate the contribution of peroxisomal dysfunction in brain as opposed to peroxisomal dysfunction in extraneuronal tissues to the migration defect. Peroxisomes were selectively reconstituted either in brain or liver of Pex5 knock-out mice, a model for Zellweger syndrome, by tissue-selective overexpression of Pex5p. We found that both rescue strains exhibited a significant correction of the neuronal migration defect despite an incomplete reconstitution of peroxisomal function in the targeted tissue. Animals with a simultaneous rescue of peroxisomes in both tissues displayed a pattern of neuronal migration indistinguishable from that of wild-type animals on the basis of cresyl violet staining and 5',3'-bromo-2'-deoxyuridine birth-dating analysis. These data suggest that peroxisomal metabolism in brain but also in extraneuronal tissues affects the normal development of the mouse neocortex. In liver-rescued mice, the improvement of the neuronal migration was not accompanied by changes in very long chain fatty acid, docosahexaenoic acid, or plasmalogen levels in brain, indicating that other metabolic factors can influence the neuronal migration process.