The role of laboratory medicine in healthcare: quality requirements of immunoassays, standardisation and data management in prospective medicine

In the last 10 years, the area of ELISA and protein-chip technology has developed and enthusiastically applied to an enormous variety of biological questions. However, the degree of stringency required in data analysis appears to have been underestimated. As a result, there are numerous published findings that are of questionable quality, requiring further confirmation and/or validation. In the course of feasibility and validation studies a number of key issues in research, development and clinical trial studies must be outlined, including those associated with laboratory design, analytical validation strategies, analytical completeness and data managements. The scope of the following review should provide assistance for defining key parameters in assay evaluation and validation in research and clinical trial projects in prospective medicine

Variant of TYR and Autoimmunity Susceptibility Loci in Generalized Vitiligo.

BACKGROUND Generalized vitiligo is an autoimmune disease characterized by melanocyte loss, which results in patchy depigmentation of skin and hair, and is associated with an elevated risk of other autoimmune diseases. METHODS To identify generalized vitiligo susceptibility loci, we conducted a genomewide association study. We genotyped 579,146 single-nucleotide polymorphisms (SNPs) in 1514 patients with generalized vitiligo who were of European-derived white (CEU) ancestry and compared the genotypes with publicly available control genotypes from 2813 CEU persons. We then tested 50 SNPs in two replication sets, one comprising 677 independent CEU patients and 1106 CEU controls and the other comprising 183 CEU simplex trios with generalized vitiligo and 332 CEU multiplex families. RESULTS We detected significant associations between generalized vitiligo and SNPs at several loci previously associated with other autoimmune diseases. These included genes encoding major-histocompatibility-complex class I molecules (P=9.05×10−23) and class II molecules (P=4.50×10−34), PTPN22 (P=1.31×10−7), LPP (P=1.01×10−11), IL2RA (P=2.78×10−9), UBASH3A (P=1.26×10−9), and C1QTNF6 (P=2.21×10−16). We also detected associations between generalized vitiligo and SNPs in two additional immune-related loci, RERE (P=7.07×10−15) and GZMB (P=3.44×10−8), and in a locus containing TYR (P=1.60×10−18), encoding tyrosinase. CONCLUSIONS We observed associations between generalized vitiligo and markers implicating multiple genes, some associated with other autoimmune diseases and one (TYR) that may mediate target-cell specificity and indicate a mutually exclusive relationship between susceptibility to vitiligo and susceptibility to melanoma

ILEI: a cytokine essential for EMT, tumor formation, and late events in metastasis in epithelial cells.

Erk/MAPK and TGFbeta signaling cause epithelial to mesenchymal transition (EMT) and metastasis in mouse mammary epithelial cells (EpH4) transformed with oncogenic Ras (EpRas). In trials to unravel underlying mechanisms, expression profiling for EMT-specific genes identified a secreted interleukin-related protein (ILEI), upregulated exclusively at the translational level. Stable overexpression of ILEI in EpH4 and EpRas cells caused EMT, tumor growth, and metastasis, independent of TGFbeta-R signaling and enhanced by Bcl2. RNAi-mediated knockdown of ILEI in EpRas cells before and after EMT (EpRasXT) prevented and reverted TGFbeta-dependent EMT, also abrogating metastasis formation. ILEI is overexpressed and/or altered in intracellular localization in multiple human tumors, an event strongly correlated to invasion/EMT, metastasis formation, and survival in human colon and breast cancer