La greffe de moelle dans les maladies héréditaires.

Since 1968, bone marrow transplantation became the first line therapy for selected metabolic and immunological hereditary disorders. Actually, advances in the supportive care in bone marrow transplantation and a better knowledge of the immunology of BMT complications has been associated with a better disease correction and an increase in long term survival. New approaches are under investigation and include: hematopoietic growth factors, enzymatic replacement and gene therapy. However at the present time BMT is still the only curative treatment for selected hereditary disorders.

LPS-binding protein and IL-6 Mark paradoxical tuberculosis immune reconstitution inflammatory syndrome in HIV patients

Background: Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) remains a poorly understood complication in HIV-TB co-infected patients initiating antiretroviral therapy (ART). The role of the innate immune system in TB-IRIS is becoming increasingly apparent, however the potential involvement in TB-IRIS of a leaky gut and proteins that interfere with TLR stimulation by binding PAMPs has not been investigated before. Here we aimed to investigate the innate nature of the cytokine response in TB-IRIS and to identify novel potential biomarkers. Methods: From a large prospective cohort of HIV-TB co-infected patients receiving TB treatment, we compared 40 patients who developed TB-IRIS during the first month of ART with 40 patients matched for age, sex and baseline CD4 count who did not. We analyzed plasma levels of lipopolysaccharide (LPS)-binding protein (LBP), LPS, sCD14, endotoxin-core antibody, intestinal fatty acid-binding protein (I-FABP) and 18 pro-and anti-inflammatory cytokines before and during ART. Results: We observed lower baseline levels of IL-6 (p = 0.041), GCSF (p = 0.036) and LBP (p = 0.016) in TB-IRIS patients. At IRIS event, we detected higher levels of LBP, IL-1RA, IL-4, IL-6, IL-7, IL-8, G-CSF (p ≤ 0.032) and lower I-FABP levels (p = 0.013) compared to HIV-TB co-infected controls. Only IL-6 showed an independent effect in multivariate models containing significant cytokines from pre-ART (p = 0.039) and during TB-IRIS (p = 0.034). Conclusion: We report pre-ART IL-6 and LBP levels as well as IL-6, LBP and I-FABP levels during IRIS-event as potential biomarkers in TB-IRIS. Our results show no evidence of the possible contribution of a leaky gut to TB-IRIS and indicate that IL-6 holds a distinct role in the disturbed innate cytokine profile before and during TB-IRIS. Future clinical studies should investigate the importance and clinical relevance of these markers for the diagnosis and treatment of TB-IRIS. Copyright: © 2013 Goovaerts et al.

Rett syndrome

Rett syndrome is one of the most common causes of complex disability in girls. It is characterized by early neurological regression that severely affects motor, cognitive and communication skills, by autonomic dysfunction and often a seizure disorder. It is a monogenic X-linked dominant neurodevelopmental disorder related to mutation in MECP2, which encodes the methyl-CpG-binding protein MeCP2. There are several mouse models either based on conditional knocking out of the Mecp2 gene or on a truncating mutation. We discuss the clinical aspects with special emphasis on the behavioral phenotype and we review current perspectives in clinical management alongside with perspectives in altering gene expression. Copyright © 2012 S. Karger AG, Basel.