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OBJECTIVE: Fever of unknown origin is a diagnostic challenge in children, especially for differentiation of systemic-onset juvenile idiopathic arthritis (systemic-onset JIA) and infectious diseases. We undertook this study to analyze the relevance of myeloid-related proteins (MRPs) 8 and 14, endogenous activators of Toll-like receptor 4, in diagnosis and pathogenesis of systemic-onset JIA. METHODS: Serum concentrations of MRP-8/MRP-14 were analyzed in 60 patients with systemic-onset JIA, 85 patients with systemic infections, 40 patients with acute lymphoblastic leukemia, 5 patients with acute myeloblastic leukemia, 18 patients with neonatal-onset multisystem inflammatory disease (NOMID), and 50 healthy controls. In addition, we investigated the link between interleukin-1beta (IL-1beta) and MRP-8/MRP-14 in systemic-onset JIA. RESULTS: Serum MRP-8/MRP-14 concentrations were significantly (P < 0.001) elevated in patients with active systemic-onset JIA (mean +/- 95% confidence interval 14,920 +/- 4,030 ng/ml) compared with those in healthy controls (340 +/- 70 ng/ml), patients with systemic infections (2,640 +/- 720 ng/ml), patients with acute lymphoblastic leukemia (650 +/- 280 ng/ml), patients with acute myeloblastic leukemia (840 +/- 940 ng/ml), and patients with NOMID (2,830 +/- 580 ng/ml). In contrast to C-reactive protein levels, MRP-8/MRP-14 concentrations distinguished systemic-onset JIA from infections, with a specificity of 95%. MRP-14 in serum of patients with systemic-onset JIA was a strong inducer of IL-1beta expression in phagocytes. CONCLUSION: The analysis of MRP-8/MRP-14 in serum is an excellent tool for the diagnosis of systemic-onset JIA, allowing early differentiation between patients with systemic-onset JIA and those with other inflammatory diseases. MRP-8/MRP-14 and IL-1beta represent a novel positive feedback mechanism activating phagocytes via 2 major signaling pathways of innate immunity during the pathogenesis of systemic-onset JIA. [ABSTRACT FROM AUTHOR]

In recent years, many mutations have been identified that affect the biosynthesis of the glycosylphosphatidylinositol anchor, a biomolecule that attaches surface molecules to cell membranes. Here, we present two second-degree cousins with unexplained patterns of seizures. Next-generation sequencing identified the homozygous c.460A>G; p.(R154G) PIGW mutation in both patients. Transfection of the mutated allele into Pigw-defective CHO cells indicated impaired enzymatic activity of the mutated PIGW product. Alkaline phosphatase did not exceed the upper normal range and flow cytometry of CD16, CD24, and CD66c on granulocytes showed subtle changes of the cellular expression of the glycosylphosphatidylinositol-anchored proteins. The patients' phenotype is therefore remarkably different from the phenotype of the only other described individual with PIGW mutations. Patients might therefore be missed when relying on traditional flow cytometry of glycosylphosphatidylinositol-anchored proteins only and we suggest that glycosylphosphatidylinositol-deficiency should be considered even with patients not showing the typical clinical phenotypes. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

The structure of the title complex, [ReBr(C(13)H(19)OP)(CO)(3)], displays a facial coordination of the three CO ligands and a κ(2)O,P coordination mode of the 2-diisopropyl-phosphino-benzaldehyde ligands. The Re-C bond distance for the CO ligand trans to the P atom is, due to its trans influence, elongated to 1.943 (3) Å, showing that this CO ligand is more weakly bound to the Re centre than the other two.