Sirolimus-Induced Combined Posterior Reversible Encephalopathy Syndrome and Lymphocytic Pneumonitis in a Renal Transplant Recipient: Case Report and Review of the Literature.

The mammalian target of rapamycin inhibitor sirolimus was introduced into clinical transplant practice in 1999. Dose-related myelosuppression and hyper lipidemia are the most common adverse effects. Pulmonary toxicity has been reported since 2004 and can cause interstitial pneumonitis, organizing pneumonia, and alveolar hemorrhage. Moreover, it can occasionally induce posterior reversible encephalopathy syndrome, as documented in scarce reports. To our knowledge; this is the 1st report of combined posterior reversible encephalopathy syndrome and lymphocytic pneumonitis to be induced by sirolimus. Here, we present a renal transplant recipient with reversible sirolimus-induced brain lesions who was diagnosed after exclusion of infections (viral, bacterial, and fungal), tumors, sarcoidosis, and autoimmune disorders. Both brain lesions and pneumonitis resolved completely after sirolimus discontinuation with excellent patient and graft outcome. Early and gradual sirolimus withdrawal can reverse posterior reversible encephalopathy syndrome and lymphocytic pneumonitis with preservation of stable graft function.

Regulatory CD56(bright) natural killer cells mediate immunomodulatory effects of IL-2Ralpha-targeted therapy (daclizumab) in multiple sclerosis.

Administration of daclizumab, a humanized mAb directed against the IL-2Ralpha chain, strongly reduces brain inflammation in multiple sclerosis patients. Here we show that daclizumab treatment leads to only a mild functional blockade of CD4(+) T cells, the major candidate in multiple sclerosis pathogenesis. Instead, daclizumab therapy was associated with a gradual decline in circulating CD4(+) and CD8(+) T cells and significant expansion of CD56(bright) natural killer (NK) cells in vivo, and this effect correlated highly with the treatment response. In vitro studies showed that NK cells inhibited T cell survival in activated peripheral blood mononuclear cell cultures by a contact-dependent mechanism. Positive correlations between expansion of CD56(bright) NK cells and contraction of CD4(+) and CD8(+) T cell numbers in individual patients in vivo provides supporting evidence for NK cell-mediated negative immunoregulation of activated T cells during daclizumab therapy. Our data support the existence of an immunoregulatory pathway wherein activated CD56(bright) NK cells inhibit T cell survival. This immunoregulation has potential importance for the treatment of autoimmune diseases and transplant rejection and toward modification of tumor immunity.

Fluorescence of hematoxylin and eosin-stained histological sections of the human spleen.

A major problem in the morphometric evaluation of human spleen is the simple but reliable determination of the border between T-cell and B-cell dependent areas, and other structures of the spleen. It was investigated whether cryostat sections of frozen surgical specimens of the human spleen and sections of paraffin-embedded specimens could be used for this purpose after being stained with haematoxylin and eosin and mounted in autofluorescence-free medium for fluorescence microscopical evaluation. Comparison was made with sections that were immunohistochemically-stained for fibronectin and collagens type II and type IV. Both in cryostat sections and paraffin sections, fluorescence was found in circumferential reticulum of periarterial lymphatic sheets, arterial terminals, arterial walls and walls of red pulp sinuses in the spleen. Evaluation was hindered by fluorescence of erythrocytes in paraffin sections but not in cryostat sections. Results were similar as those obtained with immunohistochemical fibronectin staining and are sufficient for morphometric evaluation or orientation in the tissue in case of neoplasia.