Type I interferonopathies in pediatric rheumatology.

Defective regulation of type I interferon response is associated with severe inflammatory phenotypes and autoimmunity. Type I interferonopathies are a clinically heterogenic group of Mendelian diseases with a constitutive activation of this pathway that might present as atypical, severe, early onset rheumatic diseases. Skin vasculopathy with chilblains and livedo reticularis, interstitial lung disease, and panniculitis are common. Recent studies have implicated abnormal responses to nucleic acid stimuli or defective regulation of downstream effector molecules in disease pathogenesis. As observed for IL1-β and autoinflammatory diseases, knowledge of the defects responsible for type I interferonopathies will likely promote the development of targeted therapy

In vitro functional correction of Hermansky-Pudlak Syndrome type-1 by lentiviral-mediated gene transfer.

Hermansky-Pudlak syndrome (HPS) is a genetic disorder characterized by oculocutaneous albinism, bleeding tendency and susceptibility to pulmonary fibrosis. No curative therapy is available. Genetic correction directed to the lungs, bone marrow and/or gastro-intestinal tract might provide alternative forms of treatment for the diseases multi-systemic complications. We demonstrate that lentiviral-mediated gene transfer corrects the expression and function of the HPS1 gene in patient dermal melanocytes, which opens the way to development of gene therapy for HPS

Risk of miscarriage in women with endometriosis: insights from in vitro fertilization cycles

Objective: To evaluate whether women with endometriosis achieving singleton pregnancies with IVF face an increased risk of miscarriage. Design: Matched case-control study. Setting: Infertility units. Patient(s): Women achieving singleton pregnancies with the use of IVF were considered. Cases were women with a history of surgery for endometriosis and those who were documented the presence of ovarian endometriomas at the time of the IVF cycle (n = 313). Controls were matched to cases by age (\ub16 months), type of cycle (fresh or frozen cycle). and study period (n = 313). Intervention(s): Retrospective review of women undergoing IVF. Main Outcome Measure(s): Rate of miscarriage before 12 weeks' gestation. Result(s): The number of miscarriages in women with and without endometriosis was similar, being 48 (15%) and 60 (19%), respectively. The odds ratio of miscarriage in affected women was 0.76 (95% confidence interval 0.50-1.16). The odds ratio adjusted for body mass index (BMI), parity, duration of infertility, and male factor infertility was 0.81 (95% confidence interval 0.53-1.25). Subgroup analyses according to the type of cycle, the number of embryos transferred, the presence of endometriomas, and the history of surgery for endometriosis did not document any subgroup at significant increased risk of miscarriage. Conclusion(s): The risk of miscarriage is not increased in women with endometriosis achieving pregnancy with the use of IVF

Truncated forms of human and simian immunodeficiency virus in infected individuals and rhesus macaques are unique or rare quasispecies

AbstractTruncated proviruses of variable sizes are present in peripheral blood mononuclear cells (PBMC) of human immunodeficiency virus type 1 (HIV-1)-infected persons and simian immunodeficiency virus (SIV)-infected rhesus macaques. Here, we investigated whether the highly deleted HIV and SIV proviruses are present in infected organisms as multiple copies or whether each truncated provirus is unique. Using end-point dilution, multiple long-distance (LD) DNA PCR assays were run in parallel using DNA extracted from PBMC of seropositive, treatment-naive persons and from lymph nodes of a rhesus monkey inoculated with cloned, full-length SIVmac239 DNA. The PCR products were titrated and mapped. Most truncated proviruses were present in the DNA samples tested as single, nonintegrated molecules that differed from one another in size and/or nucleotide sequence. These results indicate that truncated primate lentiviral sequences found in infected tissues are unique or rare quasispecies that do not replicate significantly