Safety and Tolerability of Manual Push Administration of Subcutaneous IgPro20 at High Infusion Rates in Patients with Primary Immunodeficiency: Findings from the Manual Push Administration Cohort of the HILO Study
JOURNAL OF CLINICAL IMMUNOLOGY
Authors: Cowan, Juthaporn; Bonagura, Vincent R.; Lugar, Patricia L.; Maglione, Paul J.; Patel, Niraj C.; Vinh, Donald C.; Hofmann, Jutta H.; Praus, Michaela; Rojavin, Mikhail A.
Abstract
Purpose To evaluate the safety and tolerability of IgPro20 manual push (also known as rapid push) infusions at flow rates of 0.5-2.0 mL/min. Methods Patients with primary immunodeficiency (PID) with previous experience administering IgPro20 (Hizentra(R), CSL Behring, King of Prussia, PA, USA) were enrolled in the Hizentra(R)Label Optimization (HILO) study (NCT03033745) and assigned to Pump-assisted Volume Cohort, Pump-assisted Flow Rate Cohort, or Manual Push Flow Rate Cohort; this report describes the latter. Patients administered IgPro20 via manual push at 0.5, 1.0, and 2.0 mL/min/site for 4 weeks each. Responder rates (percentage of patients who completed a predefined minimum number of infusions), safety outcomes, and serum immunoglobulin G (IgG) trough levels were evaluated. Results Sixteen patients were treated; 2 patients (12.5%) discontinued at the 1.0-mL/min level (unrelated to treatment). Responder rates were 100%, 100%, and 87.5% at 0.5-, 1.0-, and 2.0-mL/min flow rates, respectively. Mean weekly infusion duration decreased from 103-108 to 23-28 min at the 0.5- and 2.0-mL/min flow rates, respectively. Rates of treatment-related treatment-emergent adverse events (TEAEs) per infusion were 0.023, 0.082, and 0.025 for the 0.5-, 1.0-, and 2.0-mL/min flow rates, respectively. Most TEAEs were mild local reactions and tolerability (infusions without severe local reactions/total infusions) was 100% across flow rate levels. Serum IgG levels (mean [SD]) were similar at study start (9.36 [2.53] g/L) and end (9.58 [2.12] g/L). Conclusions Subcutaneous IgPro20 manual push infusions at flow rates up to 2.0 mL/min were well tolerated and reduced infusion time in treatment-experienced patients with PID.
Bimodal size distribution immuno-quantum dots for fluorescent western blotting assay with high sensitivity and extended dynamic range
MICROCHIMICA ACTA
Authors: Yan, Wannian; Fan, Lingzhi; Li, Jin; Wang, Yijiang; Han, Huanxing; Tan, Fei; Zhang, Pengfei
Abstract
A highly sensitive quantum dot (QD)-based western blot assay with extended dynamic range was developed. Bimodal size distribution QD (BQ) immunoprobes composed of small size single QD (7.3 nm) and big size QD nanobead (QB) (82.9 nm) were employed for fluorescent western blot immunoassay on a membrane. Small size QD immunoprobes contributed to wider dynamic range of assay, while big size QB immunoprobes provided higher detection sensitivity. This BQ-based western blot assay can achieve a wide dynamic range (from 7.8 to 4000 ng IgG) and is nearly as sensitive as commercial available ultrasensitive chemiluminescent methods, just using a simple gel imager with UV light (365 nm) excitation and red light filter (610 nm). The fluorescent signals of BQ western blot were stable for 10 min, while chemiluminescent signals faded after 1 min. Moreover, this BQ immunoprobe was utilized for the detection of housekeeping protein and specific target proteins in complex cell lysate samples. The limit of detection of housekeeping protein is 0.25 mu g of cell lysate, and the signal intensities were proportional to loading protein amount in a wide range from 0.61 to 80 mu g. We believe that this new strategy of bimodal size distribution nanoparticles can also be expanded for other functional nanoparticle-based biological assays to improve the sensitivity and extend the dynamic range.Graphical abstract