BACKGROUNDHereditary angioedema is characterized by recurrent attacks of angioedema of the skin, larynx, and gastrointestinal tract. Bradykinin is the key mediator of symptoms. Icatibant is a selective bradykinin B2 receptor antagonist.METHODSIn two double-blind, randomized, multicenter trials, we evaluated the effect of icatibant in patients with hereditary angioedema presenting with cutaneous or abdominal attacks. In the For Angioedema Subcutaneous Treatment (FAST) 1 trial, patients received either icatibant or placebo; in FAST-2, patients received either icatibant or oral tranexamic acid, at a dose of 3 g daily for 2 days. Icatibant was given once, subcutaneously, at a dose of 30 mg. The primary end point was the median time to clinically significant relief of symptoms.RESULTSA total of 56 and 74 patients underwent randomization in the FAST-1 and FAST-2 trials, respectively. The primary end point was reached in 2.5 hours with icatibant versus 4.6 hours with placebo in the FAST-1 trial (P=0.14) and in 2.0 hours with icatibant versus 12.0 hours with tranexamic acid in the FAST-2 trial (P<0.001). In the FAST-1 study, 3 recipients of icatibant and 13 recipients of placebo needed treatment with rescue medication. The median time to first improvement of symptoms, as assessed by patients and by investigators, was significantly shorter with icatibant in both trials. No icatibant-related serious adverse events were reported.CONCLUSIONSIn patients with hereditary angioedema having acute attacks, we found a significant benefit of icatibant as compared with tranexamic acid in one trial and a nonsignificant benefit of icatibant as compared with placebo in the other trial with regard to the primary end point. The early use of rescue medication may have obscured the benefit of icatibant in the placebo trial. (Funded by Jerini; ClinicalTrials.gov numbers, NCT00097695 and NCT00500656.)

Dendritic Cells (DC) are potent antigen presenting cells and are considered important cellular components for immunoregulation. Cord blood (CB) has recently been recognized as an alternative source of stem cells however transplant recipients often experience delayed immune reconstitution. DC may be useful for enhancing immunity against infection and/or malignant disease. In this study, we explored the use of 10% autologous plasma to generate DC from CB adherent MNC. CB was collected from scheduled Cesaren-section or vaginal deliveries and CB MNC were collected by Ficoll-hypaque density centrifugation. Plasma was recovered from the supernatant and heat inactivated at 56°C. The plastic adherent population was cultured in AIM-V with 10% CB plasma supplemented with GM-CSF (100 ng/ml) TNF-α, (2.5 ng/ml), Flt3-Ligand (25 ng/ml) and IL-4 (5 ng/ml). Control without cytokines and/or 10% plasma were also cultured. Cytokine cultured cells developed characteristic DC morphology with many slender, elongated, and/or numerous fine membrane projections. By immunohistochemistry these morphologically distinct cells were CD1a+ and CD14-. Control cells maintained macrophage appearance of large adherent cells without membranous projections and were CD14+ but CD1a-. Cytokine cultured cells had significant phenotypic changes(confluent culture vs. day 0, mean ±SEM) consistent with DC expression of CD1a+CD80+ (7.5±1.4% vs. 0.9±0.2%, p<0.01, n=6) (8-fold) and CD1a+CD80+CD86+ (5.3±1.2% vs. 0.6±0.2%, p<0.01, n=6)(10-fold) with a fall of CD14+ (5.6±1.6% vs. 33.2±5.7, p<0.01, n=6). Allogenic primary Mixed Lymphocyte Reaction (MLR) with T-cells enriched by column was significantly increased over CB adherent cells by 351±49% (p=0.001, n=3) at ratio of 1:5 and 160±13% (p=0.002, n=3) at ratio of 1:25 (DC:T-cell). In summary, DC can effectively be generated with 10% autologous plasma from CB adherent MNC, acquire co-stimulatory molecules and are powerful stimulators of T-cell alloreactivity.