Kappa free light chains: Diagnostic performance in multiple sclerosis and utility in a clinical laboratory.

BACKGROUND: Automated, technically simple analytical methods offering objective results are highly valued in clinical laboratories. Kappa free light chains (KFLC) in cerebrospinal fluid (CSF) are promising multiple sclerosis (MS) biomarkers, particularly kappa (K) index. METHODS: KFLC were determined in CSF and serum samples of patients diagnosed with MS, clinically/radiologically isolated syndrome (N, 39), and controls (N, 152; inflammatory and non-inflammatory neurological disorders). Diagnostic performance of several KFLC parameters, previously determined oligoclonal band (OCB) testing, and IgG index, was assessed. A K index decision threshold for sample screening was identified and reduction in performed OCB analyses estimated accordingly. RESULTS: Higher KFLC parameters were detected in the MS group and K index performed best among them (AUC 0.92). At a 7.25 cut-off it showed better sensitivity (85% vs. 77%) though less specificity (88% vs. 91%) than OCBs. Comparatively, IgG index's performance was inferior (AUC 0.83). A decision K index threshold of 2.55 (97% sensitivity) would reduce OCB testing by 52% in the studied population. CONCLUSIONS: The proposed 7.25 cut-off could assist MS diagnostics and identify some false negative cases from OCB studies. Sequential algorithms using K index for the decision to perform OCB detection would improve laboratory efficiency and substantially reduce costs.

Teleost fish larvae adapt to dietary arachidonic acid supply through modulation of the expression of lipid metabolism and stress response genes.

Dietary fatty acid supply can affect stress response in fish during early development. Although knowledge on the mechanisms involved in fatty acid regulation of stress tolerance is scarce, it has often been hypothesised that eicosanoid profiles can influence cortisol production. Genomic cortisol actions are mediated by cytosolic receptors which may respond to cellular fatty acid signalling. An experiment was designed to test the effects of feeding gilthead sea-bream larvae with four microdiets, containing graded arachidonic acid (ARA) levels (0·4, 0·8, 1·5 and 3·0 %), on the expression of genes involved in stress response (steroidogenic acute regulatory protein, glucocorticoid receptor and phosphoenolpyruvate carboxykinase), lipid and, particularly, eicosanoid metabolism (hormone-sensitive lipase, PPARα, phospholipase A2, cyclo-oxygenase-2 and 5-lipoxygenase), as determined by real-time quantitative PCR. Fish fatty acid phenotypes reflected dietary fatty acid profiles. Growth performance, survival after acute stress and similar whole-body basal cortisol levels suggested that sea-bream larvae could tolerate a wide range of dietary ARA levels. Transcription of all genes analysed was significantly reduced at dietary ARA levels above 0·4 %. Nonetheless, despite practical suppression of phospholipase A2 transcription, higher leukotriene B4 levels were detected in larvae fed 3·0 % ARA, whereas a similar trend was observed regarding PGE2 production. The present study demonstrates that adaptation to a wide range of dietary ARA levels in gilthead sea-bream larvae involves the modulation of the expression of genes related to eicosanoid synthesis, lipid metabolism and stress response. The roles of ARA, other polyunsaturates and eicosanoids as signals in this process are discussed.

Dietary lecithin source affects growth potential and gene expression in Sparus aurata larvae.

Soybean lecithin (SBL), used as a phospholipid source in larval fish diets, may compromise growth and survival in marine species, and affect gene expression, due to differences in fatty acid composition relative to marine lecithins (ML). The potential of SBL as a phospholipid source in gilthead seabream microdiets as compared to ML was evaluated. Two stocking densities were tested in order to exacerbate possible dietary effects: 5 and 20 larvae L(-1). Larvae reflected dietary fatty acid profiles: linoleic acid was higher, whereas eicosapentaenoic and arachidonic acids were lower in SBL fed groups than in ML fed larvae. Highest stocking density decreased survival, and led to elevated saturates and lower docosahexaenoic acid levels in polar lipid. Muscle histology observations showed hindered growth potential in SBL fed larvae. Despite similar cortisol levels between treatments, higher glucocorticoid receptor (GR), as well as hormone-sensitive lipase (HSL) mRNA levels in SBL fed groups revealed a role for fatty acids in gene regulation. Further analysed genes suggested these effects were independent from the hypothalamus-pituitary-interrenal axis control and the endocannabinoid system. Cyclooxygenase-2 and gluconeogenesis seemed unaffected. For the first time in fish, a link between dietary lecithin nature and HSL gene transcription, perhaps regulated through GR fatty acid-induced activation, is suggested. Enhanced lipolytic activity could partly explain lower growth in marine fish larvae when dietary ML is not provided.