Activation of dendritic antigen-presenting cells expressing common heat shock protein receptor CD91 during induction of psoriasis.

BACKGROUND: Psoriasis is a common and chronic relapsing inflammatory skin disorder. Although a role for T cells in mediating the induction and maintenance of psoriatic lesions is well established, mechanisms responsible for activation of T cells by antigen-presenting cells (APCs) during disease relapse are poorly understood. OBJECTIVES: (i) To determine whether expression of the common heat shock protein (HSP) receptor CD91 correlated with development of psoriasis in a mouse model of psoriasis, (ii) to characterize the lesional cells on which CD91 was expressed, and (iii) to investigate whether CD91+ cells in psoriasis showed signs of activation. METHODS: Two systems were used in order to study the above-mentioned objectives: (i) skin biopsies taken directly from patients with psoriasis (either psoriatic plaques or symptomless prepsoriatic skin) or from healthy donors, respectively, or (ii) (human) skin biopsies collected during development of psoriasis using a novel xenograft mouse model of psoriasis. The skin samples were then either processed for analysis by light microscopy, or labelled with fluorochrome-conjugated antibodies and analysed by confocal laser scanning microscopy. RESULTS: We observed a markedly increased number of CD91+ cells which paralleled development of new psoriatic lesions in the psoriasis mouse model and in established psoriatic plaques compared with symptomless prepsoriatic or healthy skin. Morphology as well as cell-specific markers showed that CD91 was predominantly expressed by dermal dendritic APCs characterized by activation of nuclear factor-kappaB signalling and the presence of tumour necrosis factor-alpha, an important proinflammatory cytokine in the immunopathogenesis of psoriasis. In addition, HSP70, a ligand for CD91, was increased in keratinocytes in close vicinity to CD91-bearing APCs in psoriatic lesions. CONCLUSIONS: These findings indicate massive presence of CD91+ dendritic cells juxtaposed to lesional keratinocytes expressing HSP70, and suggest a novel pathophysiological pathway and therapeutic target for this chronic inflammatory skin disease.

[Meningococcal epidemic in a boarding school: a rifampicin-resistant secondary case while under chemoprophylaxis]. / Meningokokken-Epidemie in einer Internatsschule: Sekundärerkrankung mit rifampicin-resistentem Erreger unter Chemoprophylaxe.

An epidemic of meningococcal disease after an influenza outbreak in a community of 49 boys (14-18 years) and 8 adults in a boarding-school is reported. The first patient died with all symptoms of the Waterhouse-Friderichsen syndrome. Several hours later, two other boys developed severe septicemia with meningitis and meningitis respectively. N. meningitidis group B susceptible to penicillin and rifampin was isolated. Within the next 8 hours, chemoprophylaxis with rifampin (600 mg twice daily) was started and maintained for 4 days for the whole community. Throat cultures had not been obtained before prophylaxis. Ten other symptomatic boys were admitted to the hospital and treated by penicillin infusion. The results of blood and cerebrospinal fluid cultures were negative, and treatment was therefore discontinued. Five days after the death of the first boy, another boy died with full-blown Waterhouse-Friderichsen syndrome while on chemoprophylaxis. The neisseriae isolated from this patient were rifampin-resistant. Serological investigations in all patients admitted to hospital revealed the existence of concomitant epidemic infection with influenza A and B in this school. We assume that the viral infection made way for the outbreak of the meningococcal disease and for the high rate of secondary meningococcal infection. Chemoprophylaxis with rifampin should not be continued for longer than 2 to 3 days, otherwise the risk of occurrence of rifampin resistant strains of N. meningitidis increases. Hitherto such strains have rarely been isolated in clinically manifest disease.

[Circulating interferon in patients with systemic lupus erythematosus. A prospective study]. / Zirkulierendes Interferon bei Patienten mit systemischem Lupus erythematodes. Eine prospektive Studie.

The serum levels of interferon (IFN) were measured in 31 patients with systemic lupus erythematosus (SLE). Among the 31 patients, 8 (25%) showed IFN in the sera: in 4 patients IFN titers of 16 U/ml, and in the other 4 patients titers of greater than or equal to 32 U/ml became detectable. Whereas antibodies to native DNA (nDNA) were present in 6 of the 8 IFN positive patients, anti-nDNA antibodies were only positive in 6 of the 23 IFN negative individuals (p less than 0.002). Eight months after the first search for IFN in the patients' sera, 6 of the 8 IFN positive patients showed reduced IFN serum levels and one each had an increased or stable IFN titer. A good correlation between IFN titers and both the anti-nDNA antibody titers and the disease activity was observed. However, there were patients with active disease, high anti-nDNA titers but no IFN in the serum.