Efficacy and safety of ligelizumab in adults and adolescents with chronic spontaneous urticaria: results of two phase 3 randomised controlled trials.

Background: Many patients with chronic spontaneous urticaria (CSU) do not achieve complete control of their symptoms with current available treatments. In a dose-finding phase 2b study, ligelizumab improved urticaria symptoms in patients with H1-antihistamine (H1-AH) refractory CSU. Here, we report the efficacy and safety outcomes from two ligelizumab phase 3 studies.

Mediation of transitional B cell maturation in the absence of functional Bruton's tyrosine kinase.

X-linked immune-deficient (Xid) mice, carrying a mutation in Bruton's tyrosine kinase (Btk), have multiple B cell lineage differentiation defects. We now show that, while Xid mice showed only mild reduction in the frequency of the late transitional (T2) stage of peripheral B cells, the defect became severe when the Xid genotype was combined with either a CD40-null, a TCRbeta-null or an MHC class II (MHCII)-null genotype. Purified Xid T1 and T2 B cells survived poorly in vitro compared to wild-type (WT) cells.

Safety and immunogenicity of a Vi polysaccharide-tetanus toxoid conjugate vaccine (Typbar-TCV) in healthy infants, children, and adults in typhoid endemic areas: a multicenter, 2-cohort, open-label, double-blind, randomized controlled phase 3 study.

Background: Enteric fever caused by Salmonella Typhi remains a major public health problem in developing countries. Typbar-TCV is a single-dose typhoid Vi polysaccharide-tetanus toxoid conjugate vaccine for persons ≥6 months of age.

Methods: Six hundred fifty-four healthy subjects aged 2-45 years enrolled in a double-blind, randomized controlled trial (RCT) received a single dose of Typbar-TCV or comparator "Vi polysaccharide" (Typbar), and 327 healthy subjects aged 6-23 months received a single dose of Typbar-TCV in an open-label trial (OLT); both received single- or multidose presentations from different lots.

Loss of the death receptor CD95 (Fas) expression by dendritic cells protects from a chronic viral infection.

Chronic viral infections incapacitate adaptive immune responses by "exhausting" virus-specific T cells, inducing their deletion and reducing productive T-cell memory. Viral infection rapidly induces death receptor CD95 (Fas) expression by dendritic cells (DCs), making them susceptible to elimination by the immune response. Lymphocytic choriomeningitis virus (LCMV) clone 13, which normally establishes a chronic infection, is rapidly cleared in C57Black6/J mice with conditional deletion of Fas in DCs.

Cytotoxic mechanisms employed by mouse T cells to destroy pancreatic β-cells.

Several cytotoxic mechanisms have been attributed to T cells participating in β-cell death in type 1 diabetes. However, sensitivity of β-cells to these mechanisms in vitro and in vivo is likely to be different. Moreover, CD4⁺ and CD8⁺ T cells may use distinct mechanisms to cause β-cell demise that possibly involve activation of third-party cytotoxic cells.

NKG2D signaling on CD8⁺ T cells represses T-bet and rescues CD4-unhelped CD8⁺ T cell memory recall but not effector responses.

CD4-unhelped CD8(+) T cells are functionally defective T cells primed in the absence of CD4(+) T cell help. Given the co-stimulatory role of natural-killer group 2, member D protein (NKG2D) on CD8(+) T cells, we investigated its ability to rescue these immunologically impotent cells. We demonstrate that augmented co-stimulation through NKG2D during priming paradoxically rescues memory, but not effector, CD8(+) T cell responses.

A superantigen interacts with leishmanial infection in antigen-presenting cells to regulate cytokine commitment of responding CD4 T cells.

Germ-line retroviral insertions in vertebrate genomes are implicated in the modulation of host immune responses. We demonstrate that CBA/J mice, which carry the proviral integrants mammary tumor virus locus 6 (Mtv6) and mammary tumor virus locus 7 (Mtv7), are less resistant to infection with the protozoan pathogen Leishmania major compared with closely related but Mtv6-negative and Mtv7-negative CBA/CaJ mice. Although both strains generated comparable L.

Development of a real-time polymerase chain reaction assay for the quantification of Leishmania species and the monitoring of systemic distribution of the pathogen.

We have developed a highly accurate and sensitive real-time polymerase chain reaction (PCR) assay to detect and quantify Leishmania parasites. The assay targets GP63, a highly conserved gene in Leishmania. We demonstrate that, with a single assay, we are able to detect and quantify several species of Leishmania.

Pleiotropic consequences of Bruton tyrosine kinase deficiency in myeloid lineages lead to poor inflammatory responses.

Bruton tyrosine kinase (Btk), a non-receptor-associated tyrosine kinase of the Tec family, appears to participate in many myeloid cell functions. We show that macrophages from X-linked immunodeficient (XID) mice lacking functional Btk cannot generate efficient bursts of reactive oxygen intermediates (ROIs). The induction of apoptotic cell death by inflammatory stimuli is also enhanced in XID macrophages.