Clinical significance of the detection of circulating immune complexes in lupus nephritis.

32 patients (22 biopsed) with lupus nephritis (LN) were observed for circulating immune complexes (IC). Solid phase Clq (SPClq) and polyethylene glycol (PEG) precipitation tests were used. The patients were studied during the clinical follow-up in different phases of disease activity. Comparative studies between each histological class of LN and corresponding forms of idiopathic glomerulonephritis (IGN) were made: no significant differences were found between either mesangial LN and stalk mesangial IGN, or between focal proliferative LN an focal proliferative IGN. However, a significant difference was found for SPClq data between diffuse proliferative LN and mesangiocapillary IGN, and between membranous LN and membranous IGN. LN, with an acute nephritic syndrome and hypocomple-mentemia, displayed SPClq data significantly above the levels of IC found in IGN with similar clinical features. IC serum data would seem an important element for the diagnosis and the clinical management of patients affected by LN. -------------------------------------------------------------------------------

The Wiskott-Aldrich syndrome protein is required for iNKT cell maturation and function.

The Wiskott-Aldrich syndrome (WAS) protein (WASp) is a regulator of actin cytoskeleton in hematopoietic cells. Mutations of the WASp gene cause WAS. Although WASp is involved in various immune cell functions, its role in invariant natural killer T (iNKT) cells has never been investigated. Defects of iNKT cells could indeed contribute to several WAS features, such as recurrent infections and high tumor incidence. We found a profound reduction of circulating iNKT cells in WAS patients, directly correlating with the severity of clinical phenotype. To better characterize iNKT cell defect in the absence of WASp, we analyzed was(-/-) mice. iNKT cell numbers were significantly reduced in the thymus and periphery of was(-/-) mice as compared with wild-type controls. Moreover analysis of was(-/-) iNKT cell maturation revealed a complete arrest at the CD44(+) NK1.1(-) intermediate stage. Notably, generation of BM chimeras demonstrated a was(-/-) iNKT cell-autonomous developmental defect. was(-/-) iNKT cells were also functionally impaired, as suggested by the reduced secretion of interleukin 4 and interferon gamma upon in vivo activation. Altogether, these results demonstrate the relevance of WASp in integrating signals critical for development and functional differentiation of iNKT cells and suggest that defects in these cells may play a role in WAS pathology

Effects of different membranes and dialysis technologies on patient treatment tolerance and nutritional parameters

There is increasing evidence that the biochemical and cellular phenomena induced by blood/membrane/dialysate interactions contribute to dialysis-related intradialytic and long-term complications. However, there is a lack of large, prospective, randomized trials comparing biocompatible and bioincompatible membranes, and convective and diffusive treatment modalities. The primary aim of this prospective, randomized trial was to evaluate whether the use of polysulfone membrane with bicarbonate dialysate offers any advantages (in terms of treatment tolerance, nutritional parameters and pre-treatment beta(2)-microglobulin levels) over a traditional membrane (Cu-prophan(R)). A secondary aim was to assess whether the use of more sophisticated methods consisting of a biocompatible synthetic membrane with different hydraulic permeability at different ultrafiltration rate (high-flux hemodialysis and hemodiafiltration) offers any further advantages. Seventy-one Centers were involved and stratified according to the availability of only the first two or all four of the following techniques: Cuprophan(R) hemodialysis (Cu-HD), low flux polysulfone hemodialysis (LfPS-HD), high-flux polysulfone high-flux hemodialysis (HfPS-HD), and high-flux polysulfone hemodiafiltration (HfPS-HDF). The 380 eligible patients were randomized to one of the two or four treatments (132 to Cu-HD, 147 to LfPS-HD, 51 to HfPS-HD and 50 to HfPS-HDF). The follow-up was 24 months. No statistical difference was observed in the algebraic sum of the end points between bicarbonate dialysis with Cuprophan(R) or with low-flux polysulfone, or among the four dialysis methods under evaluation. There was a significant decrease in pre-dialysis plasma beta(2)-microglobulin levels in high-flux dialysis of 9.04+/-10.46 mg/liter (23%) and in hemodiafiltration of 6.35+/-12.28 mg/liter (16%), both using high-flux polysulfone membrane in comparison with Cuprophan(R) and low-flux polysulfone membranes (P=0.032). The significant decrease in pre-dialysis plasma beta(2)-microglobulin levels could have a clinical impact when one considers that beta(2)-microglobulin accumulation and amyloidosis are important long-term dialysis-related complications