[Vogt-Koyanagi-Harada syndrome]. / Vogt-Koyanagi-Harada-syndroom.

BACKGROUND: Vogt-Koyanagi-Harada syndrome is rare in the Netherlands. However, in Asia it is one of the most common causes of panuveitis. The syndrome is characterised by a combination of panuveitis, pleocytosis in cerebral spinal fluid with or without neurological function loss, alopecia and depigmentation of body hair. CASE DESCRIPTION: A 40-year-old male with no previous medical history visited the emergency department with unexplained bilateral visual symptoms and optic disc swelling. In addition to the latter, further tests only showed pleocytosis in cerebral spinal fluid. In the months following the initial presentation, vision was restored but the patient developed panuveitis, extensive depigmentation, and loss of body hair. On further investigation, the patient reported having a great-grandfather from Indonesia. CONCLUSION: Vogt-Koyanagi-Harada syndrome should be considered in patients of Asian descent presenting with panuveitis, alopecia and depigmentation of body hair. Early diagnosis and treatment can prevent permanent visual injury.

Differential regulation and function of the Fas/Fas ligand system in human trophoblast cells.

Trophoblast rejection, which is characterized by increased apoptosis, is mediated by T helper (Th)-1, or proinflammatory, cytokines, whereas Th-2, or anti-inflammatory, cytokines confer immune protection and facilitate implantation. We investigated the role of both types of cytokines on the expression and function of the Fas/Fas ligand (FasL) apoptotic pathway in trophoblast cells. First-trimester human trophoblast primary-culture cells as well as A3 and HTR/8 trophoblast cell lines were treated with proinflammatory cytokines such as interferon-gamma (IFN-gamma) and tumor necrosis factor alpha (TNFalpha) and with the anti-inflammatory cytokines interleukin (IL)-6 and IL-10. Sensitivity to Fas-mediated apoptosis was measured using an activating anti-Fas monoclonal antibody. Cell viability was evaluated using the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) and CellTiter 96 assay. Fas/FasL mRNA and protein expression levels were determined using reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis, respectively. Trophoblast cells normally express FasL, but low levels of Fas, and they are resistant to Fas-mediated apoptosis. IFN-gamma and TNFalpha promote Fas expression and sensitivity, whereas IL-6 and IL-10 increase the resistance of trophoblast cells to Fas-mediated apoptosis. Furthermore, IL-10 treatment activates FLICE-like inhibitory protein (FLIP), a downstream inhibitor of Fas apoptotic signaling. Although trophoblast cells express Fas, susceptibility to Fas does not necessarily correlate with its expression. In this study, we demonstrate that Th-2 cytokines increase the resistance of trophoblast cells to Fas-mediated apoptosis either by inhibiting Fas expression or by inducing FLIP activation. This "trophoblast-cytokine-Fas/FasL triad" determines the ability of the Fas/FasL system to regulate trophoblast viability and, consequently, the success or failure of pregnancy.