MHC class II deficiency cured by unrelated mismatched umbilical cord blood transplantation: case report and review of 68 cases in the literature.

MHC class II deficiency is a rare and fatal form of primary combined immunodeficiency caused by a lack of T-cell-dependent humoral and cellular immune response to foreign antigens, which can only be cured by allogenic stem cell transplantation. In the literature search, we identified 68 cases of HSCT in MHC class II deficiency in the last 14 yr. Pre- and post-transplant MHC class II deficiency is complicated by overwhelming viral infections, a high incidence of GvHD, and graft failure with a poor overall survival rate below 50%.

Saving the red baby: successful allogeneic cord blood transplantation in Omenn syndrome.

Haematopoietic stem cell transplantation is the treatment of choice for severe primary immunodeficiencies, but only has moderate prognosis in Omenn syndrome as it is complicated by highly activated Omenn T-cells resulting in delayed T-cell engraftment and a high rate of graft failure. A 6 1/2 months old patient with a previously unknown compound heterozygous defect within the RAG1 gene (R474C; R975W) underwent 8/10 HLA-matched cord blood transplantation after myeloablative conditioning. Immune reconstitution was impressive with T-, B- and NK-cells reaching the median of age-dependent reference values within twelve, four and two months respectively.

An immunodeficiency disease with RAG mutations and granulomas.

We describe three unrelated girls who had an immunodeficiency disease with granulomas in the skin, mucous membranes, and internal organs. All three girls had severe complications after viral infections, including B-cell lymphoma associated with Epstein-Barr virus (EBV). Other findings were hypogammaglobulinemia, a diminished number of T and B cells, and sparse thymic tissue on ultrasonography.

High nerve growth factor receptor (p75NTR) expression is a favourable prognostic factor in paediatric B cell precursor-acute lymphoblastic leukaemia.

Nerve growth factor (NGF) plays a pivotal role in cellular survival/death decisions with the low affinity receptor p75NTR predominately transmitting anti-proliferative signals. In spite of its established role in B-cell function and identification as a prognostically favourable marker in a number of malignancies, little is known about the expression pattern and prognostic significance of p75NTR in B cell precursor-acute lymphoblastic leukaemia (BCP-ALL). p75NTR expression was prospectively studied on primary ALL-blasts in a cohort of paediatric patients with common ALL (n = 86) and preB-ALL (n = 34) treated within the Co-operative study group for childhood acute lymphoblastic leukaemia (CoALL) protocol, CoALL06-97.

Survivin and its prognostic significance in pediatric acute B-cell precursor lymphoblastic leukemia.

Background And Objectives: Impaired apoptosis, mediated by members of the inhibitor of apoptosis proteins (IAP) family such as survivin, is thought to contribute to leukemic cell survival. In contrast to low expression of survivin in normal differentiated adult tissues, very high levels of survivin have been described in a number of different tumors. Overexpression of survivin was found to correlate with poor prognosis in a variety of cancers including hematologic malignancies.

Topical tacrolimus is effective against eczema in Wiskott-Aldrich syndrome (WAS).

Unlabelled: The Wiskott-Aldrich syndrome is a rare X-linked immunodeficiency characterized by microplatelet thrombocytopenia and eczema. Eczema may be severe and facilitate entry of microorganism into the host.

Conclusion: We report for the first time that eczema in infants with WAS can be effectively treated with topical ttacrolimus.

A single intravenous dose of prednisolone induces phosphatidylserine externalization, loss of surface marker expression and a 24-h net increase in human peripheral blood lymphocytes ex vivo.

To understand how corticosteroids act; a characterization of their effects on lymphocytes is necessary. The effect of in vivo corticosteroids on lymphocyte subpopulations, their surface molecules and externalization of phosphatidylserine (apoptosis) is examined. In a crossover study, a single, intravenous dose of 2 mg/kg prednisolone or saline was given to six male adult human volunteers.

Identification of candidate target antigens for antibody-based immunotherapy in childhood B-cell precursor ALL.

Background: Contemporary risk adapted treatment protocols for childhood acute lymphoblastic leukemia (ALL) rely on accurate risk assessment strategies for disease re-occurrence by incorporating clinical parameters as well as immunological, molecular and cytogenetic features of the blasts at initial manifestation. Additional risk stratification is provided by analysis of the IN VITRO and IN VIVO response of the blasts towards standard chemotherapy. Despite adapted therapies, a number of children with good and bad prognostic factors still fail therapy.

Immune reconstitution inflammatory syndrome (IRIS) due to Bacille Calmette Guerin (BCG) in an HIV-positive child.

We describe the development of a localized Mycobacterium bovis-BCG infection in association with insertion of HAART in an 18-month-old HIV-infected and BCG-vaccinated child.

Delayed diagnosis and complications of Fanconi anaemia at advanced age--a paradigm.

Fanconi anaemia (FA) is a rare recessive DNA repair disorder clinically characterised by congenital malformations, progressive bone marrow failure and a high propensity for developing malignancies at an early age, predominantly acute myeloid leukaemia (AML) and squamous cell carcinoma. It is conceivable that a number of patients with hypomorphic mutations are not diagnosed as FA until severe complications in the treatment of a malignancy occur. Here, we report on a patient with FA-A, diagnosed only at the age of 49 years due to persistent pancytopenia and myelodysplastic syndrome/AML induced by a first cycle of chemotherapy for bilateral metachronic breast cancer.

[Connective tissue diseases in childhood].

Connective tissue diseases are a heterogeneous group of chronic multisystem inflammatory disorders including systemic lupus erythematosus (SLE), progressive systemic sclerosis (PSS), dermato- (DM) and polymyositis (PM), mixed connective tissue disease (MCTD), and Sjögren's syndrome (SS). Patients can present with similar clinical features, particularly during the first onset of symptoms, which frequently makes the diagnosis of a specific disease difficult. The incidence of connective tissue diseases is much lower in children than adults; however, the clinical picture is more variable.

Nuclear factor kappaB essential modulator-deficient child with immunodeficiency yet without anhidrotic ectodermal dysplasia.

Background: Amorphic mutations in the X-linked nuclear factor kappaB essential modulator ( NEMO ) gene cause Incontinentia pigmenti, which is lethal in hemizygous male patients. Hypomorphic NEMO mutations in male patients lead to anhidrotic ectodermal dysplasia (EDA) with immunodeficiency.

Objective: To report the clinical features of a child bearing a NEMO mutation who displayed an immunodeficiency without EDA.

Congenital disorder of glycosylation type Ik (CDG-Ik): a defect of mannosyltransferase I.

This study describes the discovery of a new inherited disorder of glycosylation named "CDG-Ik." CDG-Ik (congenital disorder of glycoslyation type Ik) is based on a defect of human mannosyltransferase I (MT-I [MIM 605907]), an enzyme necessary for the elongation of dolichol-linked chitobiose during N-glycan biosynthesis. Mutations in semiconserved regions in the corresponding gene, HMT-1 (yeast homologue, Alg1), in two patients caused drastically reduced enzyme activity, leading to a severe disease with death in early infancy.

Diagnostic difficulties in childhood bilateral thalamic astrocytomas.

We report on two children with bilateral thalamic astrocytomas. The first patient developed psychomotor regression at the age of 20 months followed by rapidly progressive ataxia, intention tremor, slurred speech, and bouts of drowsiness. Magnetic resonance imaging (MRI) of the brain showed swelling and high signal intensity in both thalami accompanied by supratentorial hydrocephalus.