Umbilical cord blood transplantation in Wiskott Aldrich syndrome.

OBJECTIVE: To report the use of umbilical cord blood (UCB) stem cell transplantation in Wiskott Aldrich syndrome (WAS) when a matched sibling donor was unavailable. METHODS: Three children with WAS received unrelated umbilical cord blood stem cell transplantation after a preparative regimen for the treatment of combined immunodeficiency diseases. The patients ranged in age from 1.9 to 7.9 years. The cord blood units were 4/6 HLA antigen matches in 2 children and 5/6 in 1 child, with molecular HLA-DR match in all 3 children. RESULTS: The time for neutrophil engraftment (ANC >500/mm(3)) was 11 to 16 days, and the average time for platelet engraftment was 36 to 49 days. One patient had no evidence of GvHD, 1 patient grade I, and 1 patient grade II. No patient had chronic GvHD. The patient with grade II GvHD also had gut involvement. Immunologic reconstitution demonstrated that cord blood stem cell transplantation resulted in consistent and stable T-, B-, and NK-cell development. Functional B-cell antibody responses revealed that 2 of the patients in whom IVIG has been discontinued had low detectable antibody responses to tetanus and diphtheria toxoid immunizations at 18 to 24 months after transplantation. CONCLUSIONS: Unrelated umbilical donor cord blood is an alternative source of stem cells for transplantation in children with WAS when a suitable HLA-matched donor is not available. Benefits of UCB include rapid and reliable recovery of immune function, low risk of GvHD, and low viral transmission rate.

Manejo del sindrome de Wiskott-Aldrich con esplenectomia y gamaglobulina venosa / Treatment of Wiskott-Aldrich syndrome with splenectomy and intravenous gammaglobulin

El síndrome de Wiskott-Aldrich es una compleja enfermedad de origen genético que compromete la función del sistema inmune y la coagulación; la mortalidad es elevada en la primera década de la vida a menos que se dé una corrección definitiva al defecto de base. Debido a que las alteraciones se presentan exclusivamente en células derivadas de la médula ósea, el tratamiento ideal es el trasplante de este órgano. Sin embargo, no siempre se puede conseguir un donante apto para este procedimiento, y deben surgir otras opciones de manejo que incrementen la sobrevida y prevengan el desarrollo de las secuelas más frecuentes. El tratamiento combinado con esplenectomía, antibióticos profilácticos y gamaglobulina humana venosa permite lograr estos objetivos, además de disminuir los costos de atención y mejorar notablemente la calidad de vida del paciente y su familia.

CD43, a molecule with multiple functions.

To initiate a specific immune response, lymphoid cells integrate a variety of signals generated through the orchestrated interaction of multiple cell surface molecules with their counter-receptors. As a result of the specific recognition of the antigen through antigen-specific receptors, and of the monitoring of their particular environment through the so-called coreceptor molecules, lymphoid cells go through elaborate processes of maturation and activation, contributing to the plasticity and sensitivity of immune response. CD43 is the major sialic acid rich protein on the surface of lymphocytes. However, the specific roles of this protein in different lymphoid cells under normal physiological conditions remain largely unknown. In this review we will mainly focus on the recent advances concerning the functions of this molecule as a coreceptor of different lymphoid cells as well as on the participation of this molecule in different pathologies.

Establishment and characterization of an atypical cell line from a patient with Wiskott-Aldrich-Syndrome and bone marrow allografting

Se aislaron blastos atípicos de la sangre periférica de un niño con síndrome de Wiskott-Aldrich y autotransplante de médula ósea. Las células fueron inmunotipificadas como monoblastos y crecieron en cultivo tisular en doble tiempo de 3 a 4 días. Las células aisladas originalmente y los cultivos iniciales, contenían antígenos tanto del virus herpes humano-6 (HHV-6) como del virus herpes humano-7 (HHV-7) y ácido desoxirribonucleico (ADN). Lo que disminuyó con la desdiferenciación celular en los cultivos subsecuentes. Los sobrenadantes de los cultivos celulares contenían cantidades moderadas de interleucina-6 (IL-6) y marcados niveles de factor estimulante de colonias-granulocito-monocítico (GM-CSF). Se discutió el caso desde el punto de vista de una posible co-patogénesis viral

Síndrome de Wiskott Aldrich: reporte de un caso / Wiskott-Aldrich syndrome: case report

Presentamos el caso de un lactante masculino con el diagnóstico de síndrome de Wiskott Aldrich y presentamos una revisión de la literatura clásica sobre este síndrome

A multiinstitutional survey of the Wiskott-Aldrich syndrome.

The Wiskott-Aldrich syndrome is an X-linked primary immunodeficiency originally characterized by the clinical triad of thrombocytopenia, eczema, and immunodeficiency. We collected clinical and laboratory information on 154 unselected patients with Wiskott-Aldrich syndrome to define better the clinical expression of this disorder. The classic triad of thrombocytopenia with small platelets, recurrent otitis media, and eczema was seen in only 27% of the study population; 5% of the study population had only infectious manifestations, and 20% of the study group had only hematologic manifestations before diagnosis. The results of immunologic evaluations varied from one patient to another and the course of the disorder varied tremendously, even within a single kindred. We conclude that many patients with Wiskott-Aldrich syndrome have an atypical presentation and that a panel of diagnostic tests is often required to establish the diagnosis. Two high-risk subgroups were identified in the study population: patients with platelet counts < 10 x 10(9)/L (< 10,000/mm3) at the time of diagnosis were at high risk of bleeding, and patients with autoimmune disorders were at increased risk of having a malignancy.

Primary immunodeficiency diseases: a presentation of 6 cases

The peripheral blood leukocytes of 6 children with clinical data suggestive of primary cellular immunodeficiencies were studied in an attempt the cellular basis of these disorders. The phenotype and function of T and B cells were investigated. According to the clinical and laboratory fetures, the patients were classified as one case of severe combined immunodeficiency (SCID), two of ataxia-telangiectasia (AT), one of Wiskott-Aldrich syndrome (WAAS), one of /edi%george syndrome (DSG), and one of cellular immunodeficiency (CID). The laboratory investigations together with the clinical manifestations permitted a diagnosis of primary immunodeficiency diseases

Long-term survival after bone marrow transplantation: a 15-year follow-up report of a patient with Wiskott-Aldrich syndrome.

In 1968 a 2-year-old boy with Wiskott-Aldrich syndrome was extremely ill with eczema, a series of life-threatening infections, and repeated hemorrhages into his skin, lungs, brain, and other internal organs. He was given high-dose cyclophosphamide therapy for immunosuppression, followed by bone marrow cells from his histocompatible, healthy sister. In the 15 years since bone marrow transplantation, he has had full T cell, partial B cell, and no hematopoietic engraftment. He has weathered the usual infectious diseases of childhood, has had no serious infections, and despite persistent thrombocytopenia has not had serious bleeding episodes.

Antibodies to nucleic acids in congenital immune deficiency states.

The presence of antibodies to native DNA, single-stranded DNA, and double-stranded RNA was determined for 37 patients with selective IgA deficiency, 11 patients with Wiskott-Aldrich syndrome, seven patients with common variable agammaglobulinemia, 14 patients with ataxia telangiectasia, six patients with intestinal lymphangiectasia, and one patient with Nezelof syndrome. Of 37 patients with selective IgA deficiency, 11 had antibodies to at least one nucleic acid; six had antibodies to native DNA, seven had antibodies to single-stranded DNA, and four had antibodies to double-stranded RNA. The only other congenital immune deficiency disease studied in which antibodies to nucleic acids were found was the Wiskott-Aldrich syndrome; in this group three of 11 patients had antibodies to native DNA. Retrospective analysis of our patients with SLE disclosed a 2.6% prevalence of IgA deficiency, a prevalence clearly higher than in the general population. These studies provide further evidence of the association between autoimmunity and abnormalities of IgA production and suggest a relationship between thymic-derived immune regulation and IgA production.

Hepatitis B virus infection in the Wiskott-Aldrich syndrome.

Testing of paired serum samples of 12 children with the Wiskott-Aldrich syndrome for the presence of hepatitis B surface antigen (HBsAg) antibody to HB, Ag, and antibody to the hepatitis B core antigen revealed evidence of hepatitis B virus infection in three. None of the three, however, developed overt clinical hepatitis or the chronic HBsAg carrier state. These data suggest that the immunologic defects seen in the Wiskott-Aldrich syndrome permit adequate immune responses to the hepatitis B virus and do not predispose to the chronic HBsAg carrier state.