Successful Bone Marrow Transplantation in a Case Of Griscelli Disease which Presented in Accelerated Phase with Neurological Involvement

Griscelli disease (GD) is a rare disorder characterized by pigment dilution, immunodeficiency and occurrence of accelerated phase consisting of hemophagocytosis, pancytopenia and neurological manifestations, Allogeneic BMT in the early period is an important modality of treatment for GD, We carried out an alloBMT from an HLA-identical sibling donor on a 4-year-old girl who presented in accelerated phase with neurological manifestations including convulsions, strabismus, severe dysarthria, ataxia and clonus, She was treated with etoposide, methylprednisolone and intrathecal methotrexate for 8 weeks and underwent alloBMT after receiving a conditioning regimen including ATG (rabbit, 10 mg/kg x 5 days), Bu/Cy. 8 x 10(8)/kg nucleated bone marrow cells were given. Engraftment occurred early and the post-BRIT period was uneventful. Currently, she is at 18 months post BMT with sustained engraftment and with a normal neurological examination except for minimal clonus, Long-term follow-up will determine the prognosis regarding the neurological findings.WoSScopu

MyosinV controls PTEN function and neuronal cell size

The tumour suppressor PTEN can inhibit proliferation and migration as well as control cell growth in different cell types1. PTEN functions predominately as a lipid phsophatase, converting PI(3,4,5)P(3) to PI(4,5)P(2), thereby antagonizing PI3K (Phosphoinositide 3-kinase) and its established downstream effector pathways2. However, much is unclear concerning the mechanisms that regulate PTEN movement to the cell membrane necessary for PTEN’s activity towards PI(3,4,5)P(3)3-5. Here we show a requirement for functional motor proteins in the control of PI3K signalling, involving a previously unknown association between PTEN and MyosinV. FRET measurements revealed that PTEN interacts directly with MyosinV, dependent on PTEN phosphorylation mediated by CK2 and/or GSK3. Inactivation of MyosinV-transport function in neurons increased cell size, which – in line with known attributes of PTEN-loss6, 7 - required PI3K and mTor. Our data demonstrate a myosin-based transport mechanism regulating PTEN function, providing new insights into the signalling networks regulating cell growth

Immunodeficiency in a child with high affinity auto-antibodies to Interleukin 12p40 and Interferon alpha. 13th Meeting, European Society for Paediatric Infectious Diseases.

Paracoccidioidomycosis (PCM) is a systemic mycosis endemic in Latin America, with a high prevalence in Brazil, Argentina, Colombia and Venezuela. The aetiologic agent of disease is a thermal dimorphic fungus, Paracoccidioides brasiliensis. A glycoprotein of 43 000D (gp43) is the major antigen of P. brasiliensis. Antibodies directed to this antigen are detected in the sera of all patients with PCM. Gp43 binds to laminin, thus participating in adhesion, invasion and pathogenesis of the fungus. As the role of antibodies in PCM is not fully understood, we decided to investigate the outcome of mice immunization with three distinct anti-gp43 MoAbs (17c, 8a and 24a) coupled with keyhole limpet haemocyanin (KLH). Results show not only the expected presence of anti Id (AB2) antibodies in the sera of these animals but also a spontaneous and increasing amount of anti-anti-Id (AB3) antibodies after the third course of immunization. Hybridomas producing both AB2 and AB3 MoAbs were obtained using spleen cells from mice immunized with MoAb 17c. AB3 MoAbs were also obtained with spleen cells of mice immunized with MoAbs 8a and 24a. It was also shown that human PCM patients' sera with high titres of anti-gp43 antibodies generate anti-Id antibodies. These data suggest that the immune response to P. brasiliensis can be spontaneously modulated by the idiotypic network.Univ Fed Sao Paulo, Dept Microbiol Imunol & Parasitol, Disciplina Imunol, BR-04023062 Sao Paulo, BrazilUniv Fed Sao Paulo, Dept Microbiol Imunol & Parasitol, Disciplina Imunol, BR-04023062 Sao Paulo, BrazilWeb of Scienc