Prevalence of infection by JC and BK polyomaviruses in kidney transplant recipients and patients with chronic renal disease.

The present study investigated the prevalence of infection by JC and BK polyomaviruses (JCV and BKV) in patients with chronic renal disease (CRD), kidney transplant recipients, and a control group of asymptomatic subjects. We tested a total of 295 urine samples. After DNA extraction, polymerase chain reaction assay was used to amplify a fragment of 173 bp of the polyomavirus T antigen, followed by analysis using the BamHI restriction endonuclease. Infection by polyomavirus was detected in 17.6% (52/295 subjects) of the subjects. Whereas 30.5% (18/59) of transplant recipients were infected, the frequency was only 22.4% (30/134) in the control subjects, and 3.9% (4/102) in the CRD group (all JCV). The vast majority of infections (88.9%; 16/18) in transplant recipients were of the BKV type, whereas this type was absent in CRD patients, and made up only 10.0% (3/30) of infections in the control group. The risk of BKV infection was 72 times greater in renal transplant patients than in asymptomatic subjects. The low frequency of infection found in CRD patients may have been related to elevated levels of urea excreted in the urine, together with reduced urine volume and cell content. These factors may combine to reduce viral load or inhibit amplification. The results of the study indicate a need for the routine screening for polyomavirus in pre- and post-transplant patients, as well as organ donors, considering that BKV infection has been associated with graft rejection in kidney transplants.

Hemophagocytic lymphohistiocytosis with neurological presentation: MRI findings and a nearly miss diagnosis.

Hemophagocytic lymphohistiocytosis (HLH) is a rare disease with rarer neurological presentation. When this occurs, diagnosis may be delayed. This report aims to call attention to clinical, laboratory, and radiological features that should prompt the correct diagnosis. A 13-year-old girl presented with progressive increase in intracranial pressure and ataxia. MRI showed a diffuse tumor-like swelling of the cerebellum with tonsillar herniation and patchy white matter post-contrast enhancement. Regression of swelling with steroids ruled out glioma and medulloblastoma, and brain lymphoma was considered. Diagnosis of HLH was reached 2 months after onset when uncontrolled fever and severe elevation of liver enzymes occurred. Two bone marrow biopsies were needed to demonstrate hemophagocytosis. Familial HLH was confirmed by perforin gene mutations. Bone marrow transplantation was performed. The early diagnosis of HLH may be life saving. Awareness of the disease is necessary to investigate its characteristic findings, thus avoiding a delay in diagnosis.

[Therapeutic relationship with the child and the adolescent affected with leukemia]. / La relazione terapeutica con il bambino e l'adolescente affetti da leucemia.

The main psychosocial purpose in treating childhood cancer is to help children and their families to face the diagnosis of cancer and subsequent consequences. Children and their families, most of whose are in front of this new diagnosis without showing any sign of failure, need our help. We should try from one side to help the child and his/her family who need a very quick support from us, from the other side a controlled and scientifically valid research, finalized to differentiate effective from non-effective interventions, should be carried on. The optimal clinical assistance is related to the application of the best discoveries nowadays available, based on evidence and applied in the local cultural context. The health care team can carefully listen to the children and their families to detect in which way they work and answer to the request of assistance that was offered to them. To modify own approach based on the level of satisfaction of families looking at the type of offered assistance could help in making better service.

Ureteral obstruction following allogeneic bone marrow transplantation in children.

Two patients with Ph + CML underwent URD-BMT after conditioning with Bu-Cy-LPAM. They developed hemorrhagic cystitis with an extremely complicated and painful course, caused by ureteral obstruction, requiring prolonged hospitalization. No virus other than cytomegalovirus was found and in both cases was attributed to Cy use. Treatment is usually conservative, but in the case of severe obstruction, a surgical approach should be considered and performed as early as possible to preserve renal function.

Rituximab for immune hemolytic anemia following T- and B-Cell-depleted hematopoietic stem cell transplantation.

The treatment of immune-mediated hemolytic anemia (IHA) complicating hematopoietic stem cell transplantation (HSCT) is often unsatisfactory. We report a case of IHA which occurred after T- and B-cell depleted unrelated donor HSCT carried out for mucopolysaccharidosis type I-H (Hurler syndrome) which was successfully treated with anti-CD20+ monoclonal antibody

Delayed clearance of apoptotic lymphoma cells allows cross-presentation of intracellular antigens by mature dendritic cells.

Single cells are deleted from the midst of living tissue during normal turnover and embryogenesis. This event is not associated with inflammation or autoimmunity. Little is known of the clearance of apoptotic cells during dangerous situations, accompanied by extensive cell death and tissue damage: when macrophages are overwhelmed by apoptotic cells, other phagocytes, including immature dendritic cells (DCs), may become involved. DCs efficiently present antigens derived from the processing of internalized apoptotic bodies to class I- and class II-restricted T cells. Antigen presentation results either in T cell activation or in their functional blockade. The outcome is influenced by pro-inflammatory maturative signals: efficient T cell cross-priming requires fully mature DCs. Here we discuss in vitro data suggesting that the number of apoptotic cells that die at a given time influences DC maturation and therefore their ability to uptake antigens from apoptotic cells and cross-activate T lymphocytes.

Dendritic cell presentation of antigens from apoptotic cells in a proinflammatory context: role of opsonizing anti-beta2-glycoprotein I antibodies.

OBJECTIVE: To verify whether opsonization of apoptotic cells skews the outcome of apoptotic cell antigen presentation by dendritic cells (DCs). METHODS: RMA cells, which were engineered with a mutant ovalbumin (OVA) protein and were devoid of the leader secretory sequence (OVA-RMA), underwent ultraviolet irradiation to induce apoptosis. Binding of anti-beta2-glycoprotein I antibodies (anti-beta2GPI) and phagocytosis of apoptotic cells were assessed by flow cytometry and confocal microscopy. Presentation of processing antigens and major histocompatibility complex (MHC) class II-restricted or MHC class I-restricted antigens was assessed using OVA-specific T cell hybridomas. RESULTS: Anti-beta2GPI facilitated presentation of epitopes from internalized apoptotic cells to MHC class II-restricted, but not to class I-restricted, T lymphocytes. DCs challenged with supernatants of apoptotic cells did not activate OVA-specific T cells, making it unlikely that anti-beta2GPI complexed with antigen released from dying cells plays a role in antigen presentation. DCs challenged with low numbers of anti-beta2GPI-opsonized apoptotic cells secreted interleukin-1beta (IL-1beta), tumor necrosis factor alpha, and IL-10 in an autocrine/paracrine manner. CONCLUSION: Opsonization influences the outcome of the disposal of low numbers of apoptotic cells by DCs. This implies that soluble factors bound to apoptotic cells modulate their immunogenicity.

Dendritic cells preferentially internalize apoptotic cells opsonized by anti-beta2-glycoprotein I antibodies.

Dendritic cells (DC) are potent antigen-presenting cells involved in the initiation of immune responses, including those directed towards self antigens. Immature DC capture soluble antigens by macropinocytosis or c-type lectin receptor-mediated endocytosis and particulate by phagocytosis, including Fc receptor-mediated phagocytosis. Apoptosis is accompanied by the clustering of intracellular autoantigens, which are also selectively cleaved and phos-phorylated, and by the exposure of anionic phospholipids (phosphatidyl-serine, PS). Anti-phospholipid antibody (aPL) detection correlates with an increased risk of developing autoimmune syndromes. In this study apoptosis was induced by UV irradiation, growth factor deprivation or exposure to protein synthesis inhibitors of murine cells and verified by confocal microscopy and flow cytometry. Apoptotic cells were recognized by a panel of anti-beta2-glycoprotein I (beta2-GPI) aPL monoclonal antibodies, but not by isotype-matched antibodies. The binding restricted to membrane domains, corresponding to apoptotic blebs, was not affected by the stimulus initiating apoptosis and was specific, since it required the association of the beta2-GPI co-factor to the apoptotic membrane. aPL-binding successfully transformed apoptotic cells in an efficient phagocytic substrate for murine immature DC, possibly skewing their immunogenicity in vivo.

Bystander apoptosis triggers dendritic cell maturation and antigen-presenting function.

Physiologic cell death via apoptosis occurs without inflammation or autoimmunity. Here, we investigated the outcome of the interaction of apoptotic cells with dendritic cells (DCs), which are potent professional APCs. DCs internalized apoptotic cells and processed them for presentation to both MHC class I- and class II-restricted T cells with an efficiency that was dependent upon the number of apoptotic cells. The latter event was accompanied by the autocrine/paracrine secretion of IL-1beta and TNF-alpha, with eventual DC maturation. High numbers of apoptotic cells, mimicking a failure of their in vivo clearance, are therefore sufficient to trigger DC maturation and the presentation of intracellular Ags from apoptotic cells, even in the absence of exogenous "danger" signals.