Rare splicing defects of FAS underly severe recessive autoimmune lymphoproliferative syndrome.

Autoimmune lymphoproliferative syndrome (ALPS) is a prototypic disorder of impaired apoptosis characterized by autoimmune features and lymphoproliferation. Heterozygous germline or somatic FAS mutations associated with preserved protein expression have been described. Very rare cases of homozygous germline FAS mutations causing severe autosomal recessive form of ALPS with a complete defect of Fas expression have been reported. We report two unrelated patients from highly inbred North African population showing a severe ALPS phenotype and an undetectable Fas surface expression. Two novel homozygous mutations have been identified underlying rare splicing defects mechanisms. The first mutation breaks a branch point sequence and the second alters a regulatory exonic splicing site. These splicing defects induce the skipping of exon 6 encoding the transmembrane domain of CD95. Our findings highlight the requirement of tight regulation of FAS exon 6 splicing for balanced alternative splicing and illustrate the importance of such studies in highly consanguineous populations.

High frequency of autoimmunization among transfusion-dependent Tunisian thalassaemia patients.

BACKGROUND: Limited data are available on the frequency of RBC alloimmunization and autoimmunization in transfusion-dependent Tunisian ß thalassaemia patients. MATERIALS AND METHODS: We analyzed the clinical and transfusion records of 130 patients (57 females and 73 males; mean age 119 months; range 12-11 months) with ß thalassaemia major and who had regular blood transfusions for periods ranging from 12 to 311 months. RESULTS: Of the 130 patients, ten (7.7%) developed RBC alloantibodies. The most common alloantibodies were directed against antigens in the Rh systems. Erythrocyte-autoantibodies as determined by a positive direct antiglobulin Coombs test, developed in 52(40%) patients with and without underlying RBC alloantibodies, thereby causing autoimmune haemolytic anaemia in eleven patients (21%). CONCLUSIONS: Autoimmunization to erythrocyte antigens is a frequent complication in patients with ß thalassaemia major. Several factors might have contributed to the high autoimmunization rate observed in this study, including non phenotypic blood exposure and alloantibody formation prior to positive Coombs test.

[Immune recovery after allogeneic stem cell transplantation: study of 19 patients]. / La reconstitution immuno hematologique en post allogreffe de moelle osseuse: etude prospective de 19 cas.

The aim of this study was to access average delays for novogeneration of myeloid and lymphoid cells after allogeneic bone marrow transplantation (BMT) outcome and factors affecting this organization. A prospective analysis over 2 years (01/01/07 to 31/12/08) enrolling 19 children treated with allogeneic intrafamilial bone marrow transplantation. Indications for bone marrow transplantation were: aplastic anemia (3 cases), bemoglobinopathies (9 cases), myelodysplastic syndrome (1 case) and primary immunodeficiency (6 cases). Different conditioning regiments were used according to the indication. The study of immune reconstitution was based on the quantitative determination of immunoglobulin and lymphocyte subpopulation. These tests were routinely requested to 1 month, 2 months, 3 months, 6 months, 9 months and 12 months. The average time of engraftment was 18 days (12-24). A rate of CD4+T lymphocytes>200/mm3 was provided within an average of 2,5 months (1-7). The average time to obtain CD8+T lymphocytes>200/mm3 was 2 months (1-5). The humoral immune reconstitution was made within an average of 2 months (1-4). A report of CD4+/CD8+T lymphocytes>I was obtained within 10 months and a half (1-24). Univaried analysis showed a correlation between the bone marrow sex matched and the faster reorganization of CD8+T cells (p=0.042). A quantity of CD34+>6 10(6)/kg was significantly associated with the recapture of a formula lymphocyte CD4+/CD8+T>1 (p=0.03) Immune recovery post bone marrow transplantation in children begins with myeloid lineage then lymphoid B then lymphoid T The inversion of the report CD4+/CD8+T lymphocytes, seems to be influenced by the high contain of CD34+cells in the graft as well as the type of conditioning.

Successful treatment of influenza A virus by oseltamivir in bone marrow transplant recipients.

INFVA is an important cause of pulmonary infections in patients receiving BMT, and is associated with considerable morbidity and mortality for a readily preventable and treatable infection. Few studies have addressed the impact of the new neuraminidase inhibitors in the prognosis of influenza after BMT. The aim of this study is to assess the impact of oseltamivir on the control of INFVA infection in BMT recipients. INFVA was screened in NPA and/or bronchoalveolar lavage using IF in all BMT recipients having respiratory symptoms. Three URTI and one associated upper and LRTI were diagnosed in three BMT recipients out of six patients admitted to the BMT unit, during eight-wk period (March and April 2008). All patients having INFVA respiratory infection were treated by oral oseltamivir 60 mg/day, begun more than 48 h after symptom onset. Respiratory symptoms disappeared within a mean of 60 h (48-96 h) of treatment. However, viral tests had remained positive for 8-39 days. Outside the initial associated URTI and LRTI, no further viral pneumonia occurred. No patient died of INFVA. Oseltamivir was well tolerated outside vomiting during the first three days of treatment in one patient. Oseltamivir appears to play an important role in the outcome of INFVA infection as well in URTI as in severe LRTI in patients receiving BMT.