The rockefeller university

Increased prevalence of latent tuberculosis infection (LTBI) has been

High-affinity B cell selection in the germinal center (GC) is governed

The establishment of latent infection and poorly characterized viral

Receptor trafficking is pivotal for the temporal and spatial control of

Sequencing of DNA extracted from environmental samples can provide key

Chronic granulomatous disease (CGD) is a primary immunodeficiency caused

Background: Interleukin 17 is involved in the pathogenesis of psoriasis, a chronic debilitating disease. Objectives: To evaluate the safety/tolerability, immunogenicity, pharmacokinetics/pharmacodynamics, and efficacy of M1095, an antieinterleukin 17A/F nanobody, in moderate-to-severe plaque psoriasis. Methods: This multicenter, double-blind, placebo-controlled dose escalation phase 1 study randomized 44 patients 4: 1 to treatment with subcutaneous M1095 (30, 60, 120, or 240 mg) or placebo biweekly for 6 weeks, in 4 ascending dose cohorts. Results: The most frequent treatment-emergent adverse events with M1095 were pruritus (n = 4) and headache (n = 3); 2 patients withdrew owing to adverse events (injection site reaction and elevated liver enzyme levels). The terminal half-life of M1095 was 11 to 12 days. The area under the curve/maximum concentration was dose proportional. Of 10 M1095-treated patients positive for antidrug antibodies, 5 showed treatment-emergent antidrug antibody responses. There was no effect on M1095 exposure. Marked decreases in psoriasis inflammatory markers were observed with M1095. By day 85, 100% and 56% of patients receiving M1095, 240 mg, achieved psoriasis area and severity index 90 and 100, respectively. Improvements in static Physician's Global Assessment and affected body surface area were also seen. Limitations: Interpretation of efficacy data is limited by the small sample size. Conclusion: Multiple subcutaneous doses of M1095 showed a favorable safety profile with dose-dependent improvements in psoriasis.

Linked Article: Albrecht et al. Br J Dermatol 2019; 180:749-55.

Eukaryotic elongation factor 2 kinase (eEF-2K), an atypical

The molecular and cellular processes that lead to renal damage and to the heterogeneity of lupus nephritis (LN) are not well understood. We applied single-cell RNA sequencing (scRNA-seq) to renal biopsies from patients with LN and evaluated skin biopsies as a potential source of diagnostic and prognostic markers of renal disease. Type I interferon (IFN)-response signatures in tubular cells and keratinocytes distinguished patients with LN from healthy control subjects. Moreover, a high IFN-response signature and fibrotic signature in tubular cells were each associated with failure to respond to treatment. Analysis of tubular cells from patients with proliferative, membranous and mixed LN indicated pathways relevant to inflammation and fibrosis, which offer insight into their histologic differences. In summary, we applied scRNA-seq to LN to deconstruct its heterogeneity and identify novel targets for personalized approaches to therapy.