Soluble IL-2 receptor and CD25 cells in psoriasis: effects of cyclosporin A and PUVA therapy.

A study was conducted to quantify soluble IL-2 receptor (sIL-2R) levels in sera of 57 chronic plaque psoriasis patients and correlate these measurements with disease activity and the number of IL-2R-positive (CD25+) lymphocytes in lesional biopsies of 11 cyclosporin A (CsA) and 13 psoralen plus ultraviolet radiation (PUVA) treated patients. Levels of sIL-2R showed a strong correlation with the psoriasis area and severity index (PASI). CsA and PUVA significantly reduced the PASI and sIL-2R levels to a similar degree after 4 weeks of treatment. Although the majority of CsA-treated patients who were biopsied showed reductions in lesional CD25+ cells, these did not reach statistical significance; in five patients biopsied who had PUVA treatment, no consistent effect on the numbers of CD25+ cells was observed. A significant correlation was found between CD25+ cells in lesional biopsies and the PASI score.     

Endometrial integrin expression in women undergoing IVF and ICSI: a comparison of the two groups and fertile controls

BACKGROUND: Integrins are thought to play a vital role in implantation. Three integrins in particular (alpha(4)beta(1), alpha(v)beta(3) and alpha(1)beta(1)) are all present during the implantation window. Defects in their expression have been linked to tubal disease, unexplained infertility and endometriosis. Hence, a reduced endometrial integrin expression would be expected in women attending for IVF due to these causes of infertility when compared with those with male factor infertility attending for ICSI. METHODS: Women attending for IVF (n = 25) and ICSI (n = 25) treatment were recruited, and timed endometrial biopsies were taken during the 'implantation window' (cycle day 20-24). A group of fertile women (n = 15) attending for sterilization was used as controls. RESULTS: There was no significant difference in integrin expression between patients undergoing IVF or ICSI. Neither did these groups differ from the control group. CONCLUSIONS: The endometrium in patients undergoing ICSI treatment is sometimes thought to be more receptive, as the infertility might be due to a male factor. This study shows that there is no significant difference in integrin expression between patients attending for IVF or ICSI and the control group. These data add to the increasing uncertainty about the clinical value of assessing the endometrium with only one marker, in this case integrins.     

Cost-effectiveness analysis of budesonide aqueous nasal spray and fluticasone propionate nasal spray in the treatment of perennial allergic rhinitis.

BACKGROUND: An economic evaluation was performed analyzing direct medical costs in Canada for the treatment of perennial allergic rhinitis (PAR) with budesonide aqueous nasal spray and fluticasone propionate nasal spray. Three hundred fourteen patients with at least a 1-year history of PAR were randomized into a double-blind, parallel-group study of 6 weeks' duration. The treatments were daily doses of budesonide 256 microg, fluticasone propionate 200 microg, or placebo. Both active treatments produced significantly lower mean scores for overall nasal symptoms compared with placebo, and both were well tolerated. Budesonide was significantly more effective than fluticasone in reducing "blocked nose." METHOD: A retrospective cost-effectiveness analysis utilizing the clinical trial data was performed on the total costs of (1) budesonide-based and (2) fluticasone-based treatment strategies, including the relative importance of the drug costs in both strategies. RESULTS: The average treatment cost per patient in Canada over 12 months in the budesonide group was CAD 389.85 which was 23.3% lower than in the fluticasone group, which was CAD 508.06, due to lower drug acquisition costs (for the year 1998). CONCLUSION: Budesonide aqueous nasal spray was shown to be more cost-effective than fluticasone propionate nasal spray in the treatment of perennial allergic rhinitis. This result is valid in the province of Ontario, Canada and in many other settings with the same structure of relative prices. The result is mainly driven by a difference in drug cost.     

The influence of FK-506 on the thymus: an immunophenotypic and structural analysis.

The influence of the powerful new immunosuppressant FK-506 on the thymus was investigated in Sprague-Dawley rats that were immunized with sheep erythrocytes and treated with FK-506 (1 mg/kg/day i.m.) for 7 days. Suppression of humoral immunity in drug-treated animals was accompanied by reductions in circulating lymphocytes bearing activation markers (interleukin-2 receptor beta-chain and OX40, activated CD4+ cells) and by striking thymic medullary atrophy. There were, however, no significant differences in thymic weights or in thymocyte numbers between experimental and control groups during the period of FK-506 administration. Reduction of the medullary compartment was visualized immunohistochemically, by decreases in major histocompatibility complex (MHC) class I- and MHC class II-positive cells and in CD37+ (mature medullary) thymocytes. Flow cytometric analysis of thymocytes showed that FK-506 induced increases in bright, Thy-1.1+ cells and in numbers of CD4+ and CD8+ thymocytes, whilst CD37+ cells were less numerous than in controls. Percentages of MHC class I- and MHC class II-positive cells varied little throughout the course of FK-506 administration. Evidence of selective damage to medullary epithelial cells, attributable to FK-506, was found at both the light and electron microscopic levels, whilst thymic macrophages in drug-treated rats displayed features of enhanced phagocytic activity, including ingestion of damaged epithelial cells. These FK-506-induced abnormalities were reversed within 14 days of drug withdrawal. These findings suggest that, like cyclosporin A, FK-506 reversibly disrupts the thymic microenvironment and may interfere with the function/maturation of T lymphocytes.     

The CTLA-4 gene region of chromosome 2q33 is linked to, and associated with, type 1 diabetes. Belgian Diabetes Registry

Susceptibility to autoimmune insulin-dependent (type 1) diabetes mellitus is determined by a combination of environmental and genetic factors, which include variation in MHC genes on chromosome 6p21 (IDDM1) and the insulin gene on chromosome 11p15 (IDDM2). However, linkage to IDDM1 and IDDM2 cannot explain the clustering of type 1 diabetes in families, and a role for other genes is inferred. In the present report we describe linkage and association of type 1 diabetes to the CTLA-4 gene (cytotoxic T lymphocyte associated-4) on chromosome 2q33 (designated IDDM12). CTLA-4 is a strong candidate gene for T cell- mediated autoimmune disease because it encodes a T cell receptor that mediates T cell apoptosis and is a vital negative regulator of T cell activation. In addition, we provide supporting evidence that CTLA-4 is associated with susceptibility to Graves' disease, another organ- specific autoimmune disease.      

Identification and characterization of intestinal Peyer's patch interferon-alpha producing (plasmacytoid) dendritic cells

Recently, a subset of murine dendritic cells (DC) has been identified that resembles human plasmacytoid (pDC) the principal interferon-alpha (IFN-alpha) producing cells in blood. In this study, C57BL/10 (B10;H2b) mice were treated with fms-like tyrosine 3 kinase Ligand (Flt3L; 10 microg/d; i.p.; 10 days) that expands DC selectively in vivo. Putative pDC (CD11c+B220+) were identified in the subepithelial dome and in interfollicular regions of intestinal Peyer's patches (PP) from both normal and Flt3L-treated animals. Freshly-isolated, immunobead-purified CD11c+ DC from PP were flow-sorted to obtain lineage- (CD11b-CD19-) CD11c+ B220+ DC (purity>96%). Flow cytometric analysis revealed that these sorted PPpDC were negative for surface markers associated with myeloid DC (CD11b) and expressed only low levels of the "lymphoid-related" DC marker CD8alphaalpha+. They expressed low levels of costimulatory molecules and moderate MHC class II. They proved weak stimulators of na?ve allogeneic (C3H; H2k) T-cell proliferation. Cytospin preparations of sorted CD11c+B220+ cells revealed plasmacytoid morphology similar to that of human pDC. Immunocytochemistry and enzyme immunoassay revealed that, within 24-hour culture with Herpes simplex virus (10 p.f.u./cell), a subpopulation of stimulated (but not unstimulated) CD11c+B220+ DC produced and secreted IFN-alpha. This novel DC subset may play important roles in innate and adaptive immune responses of the gut and in the regulation of mucosal immune reactions.