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IdeS is a streptococcal protease that cleaves IgG antibodies into F(ab’)2 and Fc fragments with a unique degree of specificity, thereby providing a novel treatment opportunity of IgG-driven autoimmune conditions and antibody mediated transplant rejection. Here we report the results from a first in man, double blinded and randomized study with single ascending doses of IdeS in healthy, male subjects. Twenty healthy subjects were given intravenous single ascending doses of IdeS. With impressive efficacy IdeS cleaved the entire plasma IgG-pool only minutes after dosing. IgG reached nadir 6-24 hours after dosing and then slowly recovered. The half-life of IdeS was 4.9 (±2.8) hours at 0.24 mg/kg with the main fraction eliminated during 24 hours. Already two hours after IdeS-dosing, the phagocytic capacity of IgG/IgG-fragments was reduced to background levels. Importantly, IdeS has the capacity to inactivate Fc-mediated effector function in vivo, was considered safe with no serious adverse events, and without dose limiting toxicity in this study. The complete, rapid, but temporary removal of IgG provides a new potent therapeutic opportunity in IgG-mediated pathogenic conditions. ClinicalTrials.gov NCT01802697.

In four phase 2 clinical trials, patients underwent imlifidase-enabled kidney transplantation, converting a positive crossmatch (+XM) to negative. Here, we present data from 39 patients enrolled in the 5-year follow-up extension trial. Patient survival, graft survival, renal function, delayed graft function (DGF) antibody mediated rejection (AMR) frequency, safety and presence of donor specific antibodies (DSAs) are presented. Data from the long-term follow-up trial (17-HMedIdeS-14); NCT 03611621) with planned visits at 1, 2, 3, and 5 years after imlifidase were combined with up to 6-month phase 2 data from 4 pivotal trials (13-HMedIdeS-02, 13-HMedIdeS-03, 14-HMedIdeS-04, 15-HMedIdeS-06). Five-year patient survival was 90% with 3 deaths occurring between 6 months and 1 year, with no deaths occurring subsequently. Death-censored graft survival was 82% (with 3 early graft losses and 3 graft losses between 2 and 5 years). Mean eGFR at 5 years was 50.1 (MDRD), 55.8 (CKD-EPI, 2021) and 52.5 (KRS, 2023) mL/min/1.73 m 2 (N = 24 patients) among functioning grafts. DSA rebounded with levels progressively decreasing over time and no increase in DSA seen between 3 and 5 years. No AMR occurred between 3 and 5 years. Furthermore, no additional safety signals assessed as related to imlifidase were reported in this cohort. At 5 years, highly-HLA sensitized patients who underwent imlifidase desensitization prior to transplantation demonstrated excellent patient and graft survival, despite their high-risk immunological profile. Imlifidase offers a viable and effective treatment option for highly sensitized patients to achieve life-saving transplantation and continued optimism is warranted.

IdeS is a streptococcal protease that cleaves IgG antibodies into F(ab')2 and Fc fragments with a unique degree of specificity, thereby providing a novel treatment opportunity of IgG-driven autoimmune conditions and antibody mediated transplant rejection. Here we report the results from a first in man, double blinded and randomized study with single ascending doses of IdeS in healthy, male subjects. Twenty healthy subjects were given intravenous single ascending doses of IdeS. With impressive efficacy IdeS cleaved the entire plasma IgG-pool only minutes after dosing. IgG reached nadir 6-24 hours after dosing and then slowly recovered. The half-life of IdeS was 4.9 ( plus or minus 2.8) hours at 0.24 mg/kg with the main fraction eliminated during 24 hours. Already two hours after IdeS-dosing, the phagocytic capacity of IgG/IgG-fragments was reduced to background levels. Importantly, IdeS has the capacity to inactivate Fc-mediated effector function in vivo, was considered safe with no serious adverse events, and without dose limiting toxicity in this study. The complete, rapid, but temporary removal of IgG provides a new potent therapeutic opportunity in IgG-mediated pathogenic conditions. Trial Registration ClinicalTrials.gov NCT01802697

Particles in exhaled air (PEx) provide samples of respiratory tract lining fluid from small airways containing, for example, Surfactant protein A (SP-A) and albumin, potential biomarkers of small airway disease. We hypothesized that there are differences between morning, noon, and afternoon measurements and that the variability of repeated measurements is larger between days than within days. PEx was obtained in sixteen healthy non-smoking adults on 11 occasions, within one day and between days. SP-A and albumin were quantified by ELISA. The coefficient of repeatability (CR), intraclass correlation coefficient (ICC), and coefficient of variation (CV) were used to assess the variation of repeated measurements. SP-A and albumin increased significantly from morning towards the noon and afternoon by 13% and 25% on average, respectively, whereas PEx number concentration and particle mean mass did not differ significantly between the morning, noon and afternoon. Between-day CRs were not larger than within-day CRs. Time of the day influences the contents of SP-A and albumin in exhaled particles. The variation of repeated measurements was rather high but was not influenced by the time intervals between measurements.

ObjectiveThe transition from fossil fuels to green energy is increasing the demand for metals, particularly critical raw materials, resulting in a drastic expansion of the metal recycling industry. However, there is limited knowledge of potential exposure risks among workers in this industry. Accordingly, in a cross-sectional study within the GreenMetalWaste project, we aim to assess metal exposure among workers from Swedish metal recycling companies.Material and MethodsWe have recruited 133 workers (83% male, average age 40 y) from 13 companies, and 70 controls from companies outside the metal recycling industry. The companies recycle metals from different end-of-life products, including e-waste, batteries, fluorescent tubes, metal scrap etc. Workers provided urine and blood after at least 4h of work, pre-shift urine, personal inhalable and respirable air measurements and a questionnaire about work tasks and occupational history.ResultsAccording to the preliminary results of air measurements, around 16% of workers had inhalable inorganic dust levels exceeding the Swedish occupational exposure limit (OEL) of 5 mg/m3 for 8h of work, with high exposures, particularly among workers conducting maintenance and manual sorting. Furthermore, measurements of 39 different metals in air samples revealed that some workers had levels of Mn, As, Co, and Pb exceeding the OEL, while others had levels of Cr, Cd, Co, Pb, Mn, Fe and Al above 10% of the OEL.ConclusionsTo assess the actual uptake of metals in workers, air measurements will be supplemented with metal analyses in biological samples of workers. This will include multiple critical raw materials as well as known toxic metals such as Pb, Hg and Cd. Based on the air measurements, we expect to observe significantly higher levels of several metals in blood and/or urine of workers compared to the controls and variations in metal exposure depending on specific work tasks.FundingThe GreenMetalWaste project was founded by The Swedish Research Councils FORTE and FORMAS (2021-01757).