A novel multidisciplinary educational programme for patients with chronic skin diseases: Ghent pilot project and first results.

Chronic inflammatory skin disorders have a major impact on the patients' health related quality of life. Preliminary studies to date have suggested that additional educational and psychological training programmes may be effective in the management of chronic skin diseases, although more rigid methodology is needed. Our purpose was to investigate the effect on quality of life of a novel multidisciplinary educational programme for patients, 18 years or older, with chronic skin diseases. The 12-week intervention encompasses cognitive education on skin and general health issues, and stress-reducing techniques. Quality of life questionnaires were used to assess the participants at baseline and at the end of the program. These comprehend Dermatology Life Quality Index (DLQI), Skindex-29, Psoriasis Disability Index (PDI) and Quality of Life Index for Atopic Dermatitis (QoLIAD). Fifty-five patients participated in six programmes since 2006. Forty-three patients completed the programme. Overall, compared to baseline, DLQI (n = 39) improved by 5.64 points (p < 0.001; SD ±6.09), Skindex-29 (n = 27) by 19.67 points (p < 0.001; SD ±17.37), PDI (n = 9) improved by 7.44 points (p = 0.019; SD ±7.60) and QoLIAD (n = 13) improved by 4.39 points (p = 0.036; SD ±6.69) by the end of the intervention. Preliminary results show that the quality of life of the patients with chronic skin diseases improved significantly after participation to the programme. These positive initial results are stimulating to set up a prospective controlled randomised trial investigating the impact on quality of life, the clinical efficacy and the cost-effectiveness of this educational intervention programme.

Induction of transient murine T cell anergy by a low molecular weight compound obtained from supernatants of human placental cultures is linked to defective phosphorylation of TCR CD3 chain.

PROBLEM: Allopregnancy induces specific transient tolerance to paternal grafts, and we know that a low molecular weight material ("filtrate") present in a human placental supernatant can do so in vitro (specific unresponsiveness) as well as in vivo, such as when preventing graft-versus-host reaction (GVH) produced by A cells injected into irradiated A x B F1s recipient. We also know by studies carried out using specific anti-V beta-specific stimulation as well as secondary and primary mixed lymphocyte reaction in major histocompatibility complex (MHC) only incompatible combinations that the material acts by inducing T cell anergy rather than clonal deletion. We explored the mechanism of such an anergy, which we know was not dependent on calcium fluxes, cyclic adenosine monophosphate (cAMP) levels, or PkC by studies of protein phosphorylation. Having observed in previous studies that expression of T cell reactivity (TcR) in anergic cells was enhanced, but that the numbers of cells expressing a given reactivity (TcR) V beta after specific stimulation in the presence of a filtrate was much higher than it should be, we monitored the receptor expression by fluorescence-activated cell sorter (FACS). METHOD OF STUDY: We used short-term stimulation of the T-cell-derived Jurkat E6-1 cells by anti-CD3 monoclonal antibody (mAb) or phorbol myristite acetate plus calcium ionophore in the presence or absence of human placental low molecular weight suppressor factors, followed by Western blotting. Transfer on nitrocellulose filters so as to allow the revelation of the phosphorylations was realized by means of a specific antiphosphotyrosin mAb. The final revelation was obtained by chemiluminescence. Similar experiments were performed on anti-V beta-stimulated BALB/c splenocytes, as well as cyproflaxin-treated cells, which are hyper-responsive in cell proliferation assays in the presence of the filtrate. In parallel, cells that were stimulated by a specific anti-V beta and were rendered specifically anergic were studied by a specific anti-V beta and were rendered specifically anergic were studied for other TcR expression using an FACS and both fluorescein isothiocyanate (FITC) and phycoerythrin (PE)-labelled, related and unrelated anti-V beta mAbs. RESULTS: The phosphorylation of the zeta chain homodimer quantitatively defective in filtrate-treated, anti-V beta 6-stimulated splenocytes as well as in Jurkatt cells. In parallel, cells from cyproflaxin-treated Jurkatt cells were showing enhanced phosphorylation of all bands. The labelling of filtrate-treated anti-V beta 6-stimulated cells by an unrelated anti-V beta (anti-V beta 8) showed double expression of V beta chains. The percentage of cells expressing this unrelated V beta (V beta 8) was normal. CONCLUSIONS: T cell anergy induced by a filtrate is linked to defective phosphorylation of the zeta-chain homodimer. The abnormal percentage of the cells expressing TcR after filtrate treatment might be due to adsorption by unstimulated cells of soluble TcR V beta-chain, possibly as a result of excess synthesis followed by membrane protease cleavage, allowing release in a soluble form of TcR V beta-chain nonspecifically captured by other cells.

Immunoactive products of placenta. VI. Induction of transient murine T cell anergy by a low-molecular-weight compound obtained from supernatants of human placental cultures.

A low-molecular-weight material present in human placental supernatant (lymphocyte proliferation inhibiting factor, LPIF, or filtrate) can induce tolerance/hyporesponsiveness in vivo. We already knew from previous experiments that this material acted only on preactivated or malignant T cells, and even the malignant cells could be rescued from its action if cells were washed quickly after contact. To understand the mechanisms of its action, we have set up systems of specific stimulation. The material inhibits anti-Vbeta-specific stimulation. In a mixed lymphocyte reaction if responder cell populations from a first MLR performed in the presence of LPIF are harvested, extensively washed to discard suppressor molecules, and restimulated by related or third-party lymphocytes in an H2-incompatible combination, the response to a third-party stimulator (a primary one) is unaffected by prior exposure to the material, which nevertheless renders the population unresponsive to restimulation by the original MHC-stimulating haplotype. Cells triggered by anti-Vbeta6 antibodies in the presence of LPIF are unable to undergo restimulation by the very same anti-Vbeta6 MoAb, while they conserve their capacity to proliferate in a primary fashion in response to the unrelated anti-Vbeta8 MoAb. When analyzed by FACS using anti-Vbeta FITC-conjugated MoAbs, cells that are unresponsive or blocked in their proliferation by the action of the filtrate after anti-Vbeta stimulation are still live and unexpectedly transiently hyperexpress the TcR. These findings confirm the requirement for T cell stimulation for suppression to be enacted and demonstrate that such is exerted by anergy rather than by clonal deletion, at least in vitro.