Search

Background A subset of T-cells expresses the B-cell marker CD20 and in rheumatoid arthritis secretes Interleukin (IL)-17. IL-17 secreting T-cells (Th17) have also been implicated in the inflammatory response in the central nervous system in multiple sclerosis (MS) and may be a potential target for elimination by biologic therapeutics. ScFvRit:sFasL comprises of a rituximab-derived antibody fragment scFvRit genetically fused to human soluble FasL that specifically eliminated T-cells. Objective To determine the presence and phenotype of CD20+T-cells in blood and brain of MS patients. Second, to determine whether scFvRit:sFasL can selectively eliminate CD20+T-cells. After CD20-selective binding, scFvRit:sFasL is designed to trigger FasL-mediated activation-induced cell death of T-cells, but not B-cells. Methods Flow cytometry and immunohistochemistry were used to screen for CD20+inflammatory T-cells in MS blood and brain tissue. ScFvRit:sFasL pro-apoptotic activity was evaluated by Annexin-V/PI staining followed by flow cytometry assessment. Results Peripheral blood (n=11) and chronic but not active lesions of MS patient brains (n=5) contained CD20+inflammatory T-cells. Activated CD20+T-cells were predominantly CD4+and secreted both IL-17 and INF-γ. ScFvRit:sFasL triggered CD20-restricted FasL-mediated activation-induced cell death in peripheral blood CD20+T-cells, but not CD20+B-cells. Conclusion CD20+inflammatory T-cells are present in blood and chronic brain lesions of MS patients. ScFvRit:sFasL selectively eliminated CD20+T-cells and may eliminate pathogenic T-cells without B-cell depletion. [ABSTRACT FROM AUTHOR]

Abstract: Background: Clinicians widely regard placental abruption as an acute event, though accumulating data point towards abruption being the end-result of chronic processes early in pregnancy, and perhaps even extending to conception. The Collaborative Perinatal Project was a prospective cohort study performed from 1959 to 1966 in the United States. Since enrolled pregnancies were managed without the biases created by modern perinatal surveillance and interventions, the natural history of disease in these data is ideal to study obstetrical complications such as placental abruption. Objective: We assessed the associations versus contributions of the clinical feature of early gestational vaginal bleeding and histologic lesions (chronic and acute) with placental abruption. Study design: Women enrolled in the Collaborative Perinatal Project (1959–1966) were used, restricting the analysis to those that delivered singleton births (n =46,364). Risks of placental abruption were compared between women with and without vaginal bleeding at <20 weeks gestation. We also examined the relationships between placental abruption and chronic and acute histologic lesions, including infarcts, decidual necrosis, presence of macrophages in the decidua, amnion or chorion, and neutrophil infiltration in the amnion, chorion, placental surface, and umbilical vein. Results: Any episode of vaginal bleeding at <20 weeks in pregnancy conferred an increased risk of placental abruption (adjusted relative risk (RR) 1.6, 95% confidence interval (CI) 1.3, 1.8). The greatest risk occurred with bleeding in both the first two trimesters (RR 3.1, 95% CI 2.3, 4.1). The presence of histologic lesions in the placenta, cord and membranes similarly carried an increased risk of placental abruption, even in the absence of vaginal bleeding. The risk of abruption was, however, highest in the presence of both histologic lesions and vaginal bleeding early in pregnancy. Conclusion: Vaginal bleeding early in pregnancy and histologic lesions of the placenta, umbilical cord, and membranes are associated with increased risk of placental abruption in later pregnancy. However, the increased risk associated with placental lesions, especially chronic inflammatory lesions, even in the absence of early vaginal bleeding, suggests that prolonged inflammation may be implicated in placental abruption. [Copyright &y& Elsevier]