Outcome of Renal Transplantation in Children Given Rabbit Anti-Thymocyte Globulin (rATG) as Induction Therapy

Background: Induction immunosuppressive therapy is used to prevent rejection and maintain allograft function in transplantation. Rabbit antithymocyte globulin (rATG), a T-cell depleting antibody, is the most commonly used induction agent for kidney transplantation.
To date there is still limited data on outcomes of pediatric kidney transplants with rATG as induction therapy.
Methods: Retrospective single-center study of first-time kidney transplant recipients ≤18 years old who received rATG induction between 2005 and 2019 at the National Kidney and Transplant Institute. Data were collected up to 1 year post-transplant.
Results: Eleven patients were included in the study. They received rATG at 1.5 mg/kg/dose (±0.3 mg/kg/dose) once a day for 3 days.
Patient survival was 100% at 6 months, and 90.9% at 1 year. Graft survival was 90.9% at 6 months, and 81.8% at 1 year. Four patients (36.4%) had a glomerular filtration rate of <60 at 1 year.
One died of sepsis at 7 months. One patient (9.1%) had acute allograft rejection with recurrence of disease, C3 glomerulopathy, on day 13. A total of 3 patients (27.3%) developed leukopenia and 4 patients (36.4%) developed thrombocytopenia. The majority were anemic at baseline (9.7 mg/dL), and a significant increase in the mean hemoglobin was seen at 4 weeks (11.6 mg/dL) to 1 year (13 mg/dL).
The incidence of recurrent infections was 9.1% (with culture growth) and 36.4% (no culture growth). Hypertension remained unchanged before and after transplant.
Conclusions: Induction with single dose rATG at 1.5 mg/kg/dose (±0.3 mg/kg/dose) for 3 days provided effective and safe outcomes in pediatric kidney transplant patients in this study.

Characterization and validation of a chronic retinal neovascularization rabbit model by evaluating the efficacy of anti-angiogenic and anti-inflammatory drugs

Aim: To establish a rabbit model with chronic condition of retinal neovascularization (RNV) induced by intravitreal (IVT) injection of DL-2-aminoadipic acid (DL-AAA), a retinal glial (Müller) cell toxin, extensive characterization of DL-AAA induced angiographic features and the suitability of the model to evaluate anti-angiogenic and anti-inflammatory therapies for ocular vascular diseases.
Methods: DL-AAA (80 mmol/L) was administered IVT into both eyes of Dutch Belted rabbit. Post DL-AAA delivery, clinical ophthalmic examinations were performed weekly following modified McDonald-Shadduck Scoring System.
Color fundus photography, fluorescein angiography (FA), and optical coherence tomography (OCT) procedures were performed every 2 or 4wk until stable retinal vascular leakage was observed. Once stable retinal leakage (12wk post DL-AAA administration) was established, anti-vascular endothelial growth factor (VEGF) (bevacizumab, ranibizumab, and aflibercept) and anti-inflammatory (triamcinolone, TAA) drugs were tested for their efficacy after IVT administration.
Fluorescein angiograms were scored before and after treatment following a novel grading system, developed for the DL-AAA rabbit model.
Results: Post DL-AAA administration, eyes were presented with moderate to severe retinal/choroidal inflammation which was accompanied by intense vitreous flare and presence of inflammatory cells in the vitreous humor.
Retinal hemorrhage was restricted to the tips of neo-retinal vessels. FA revealed maximum retinal vascular leakage at 2wk after DL-AAA injection and then persisted as evidenced by stable mean FA scores in weeks 8 and 12.
Retinal vascular angiographic and tomographic features were stable and consistent up to 36mo among two different staggers induced for RNV at two different occasions. Day 7, mean FA scores showed that 1 µg/eye of bevacizumab, ranibizumab, aflibercept and 2 µg/eye of TAA suppress 65%, 90%, 100% and 50% retinal vascular leakage, respectively.
Day 30, bevacizumab and TAA continued to show 66% and 44% suppression while ranibizumab effect was becoming less effective (68%).
In contrast, aflibercept was still able to fully (100%) suppress vascular leakage on day 30.
On day 60, bevacizumab, ranibizumab and TAA showed suppression of 7%, 12%, and 9% retinal vascular leakage, respectively, however, aflibercept continued to be more effective showing 50% suppression of vascular leakage.
Conclusion: The DL-AAA rabbit model mimics RNV angiographic features like RNV and chronic retinal leakage. Based on these features the DL-AAA rabbit model provides an invaluable tool that could be used to test the therapeutic efficacy and duration of action of novel anti-angiogenic formulations, alone or in combination with anti-inflammatory compounds.
Keywords: DL-2-aminoadipic acid; animal model; anti-vascular endothelial growth factor drugs; chronic wet age-related macular degeneration; fluorescein angiography; retinal neovascularization.

Passive immunization with anti– chimeric protein PilQ/PilA -DSL region IgY does not protect against mortality associated with Pseudomonas aeruginosa sepsis in a rabbit model

Background: Pseudomonas aeruginosa sepsis is associated with unacceptably high mortality and, for many of those who survive, long-term morbidity.
The aims of this study were to the production of IgY against chimeric protein pilQ-pilA-DSL region and killed- whole-cell Pseudomonas aeruginosa O1 (PAO1) strain and their efficacy for immunoprophylaxis of sepsis caused by P. aeruginosa in a rabbit model.
Methods: Specific IgY was obtained by immunization of hens.
The purity of IgY was determined by SDS-PAGE analysis. The effect of IgY on growth and hydrophobicity of P. aeruginosa were performed through time-kill assay and microbial adhesion to hydrocarbons test (MATH), respectively.
The efficacy of specific IgYs was examined against P. aeruginosa sepsis in a rabbit model. The rabbits were monitored for 72 h to record physiological characters and survival.
Hematologic factors, C-reactive protein, pro-inflammatory cytokines, and bacterial count from blood and solid organs were measured, periodically.
Results: We found that the growth inhibitory effect of the anti- killed whole cell IgY was higher than anti-pilQ-pilA IgY (P < 0.001).
The hydrophobicity effect of PAO1 increased when bacteria were opsonized by anti- killed whole cell IgY while the hydrophobicity activity was decreased following incubation of PAO1 with anti-pilQ-pilA IgY in a broth medium (P < 0.001).
Following intravenous (IV) administration of produced IgYs, no significant difference was observed in the survival, decrease in inflammatory mediators and clinical symptoms between the groups 48h post infection (P > 0.05).
Moreover, no considerable decrease was observed in the bacterial load of blood, lungs and kidneys in rabbits treated with specific IgYs and control groups (P > 0.05).
No bacteria were found in the spleen and liver samples from infected rabbits.
Conclusion: Although produced IgYs had a good immunoreactivity, IV immunization of IgYs was not protective against P. aeruginosa sepsis in the rabbit model. Further studies are needed to assess the immune response and decreasing mortality rate using the rabbit sepsis model.

Anti-virulence Bispecific Monoclonal Antibody Mediated Protection Against Pseudomonas aeruginosa Ventilator-Associated Pneumonia in a Rabbit Model

Ventilator-associated pneumonia is an important clinical manifestation of the nosocomial pathogen Pseudomonas aeruginosa.
We characterized the correlates of protection of MEDI3902, a bispecific human IgG1 mAb that targets the P. aeruginosa type-3-secretion PcrV protein and the Psl exopolysaccharide, in a rabbit model of ventilator-associated pneumonia using lung-protective, low-tidal volume mechanical ventilation.
Rabbits infused with MEDI3902 prophylactically were protected, whereas those pretreated with irrelevant isotype-control IgG (c-IgG) succumbed between 12 and 44 hours post infection [100% (8/8) vs. 0% (8/8) survival, P<0.01 by log-rank test].
Lungs from rabbits pretreated with c-IgG, but not those with MEDI3902, had bilateral, multifocal areas of marked necrosis, hemorrhage, neutrophilic inflammatory infiltrate, diffuse fibrinous edema in alveolar spaces.
All rabbits pretreated with c-IgG developed worsening bacteremia that peaked at the time of death, whereas only 38% (3/8) rabbits pretreated with MEDI3902 developed such high-grade bacteremia (two-sided Fisher’s exact test, P=0.026).
Biomarkers associated with acute respiratory distress syndrome were evaluated longitudinally in blood samples collected every 2-4 hours to assess systemic pathophysiological changes in rabbits pretreated with MEDI3902 or c-IgG.

Rabbit Polyclonal antibody Anti-CRBN

Anti-CRBN ImmunoStep 50 µg 418.8 EUR

Polyclonal Goat anti-GST α-form

GST-ANTI-1 Detroit R&D 50 uL 336 EUR

Polyclonal Goat anti-GST μ-form

GST-ANTI-2 Detroit R&D 50 uL 336 EUR

Polyclonal Goat anti-GST p-form

GST-ANTI-3 Detroit R&D 50 uL 336 EUR

SensiTek Anti-Rabbit

ABE008 ScyTek Laboratories 8 ml 85.2 EUR

SensiTek Anti-Rabbit

ABE015 ScyTek Laboratories 15 ml 96 EUR

SensiTek Anti-Rabbit

ABE125 ScyTek Laboratories 125 ml 211.2 EUR

SensiTek Anti-Rabbit

ABE500 ScyTek Laboratories 500 ml 504 EUR

SensiTek Anti-Rabbit

ABE999 ScyTek Laboratories 1000 ml 853.2 EUR

UltraTek Anti-Rabbit

ABK008 ScyTek Laboratories 8 ml 96 EUR

UltraTek Anti-Rabbit

ABK015 ScyTek Laboratories 15 ml 117.6 EUR

UltraTek Anti-Rabbit

ABK125 ScyTek Laboratories 125 ml 273.6 EUR

UltraTek Anti-Rabbit

ABK500 ScyTek Laboratories 500 ml 664.8 EUR

UltraTek Anti-Rabbit

ABK999 ScyTek Laboratories 1000 ml 1120.8 EUR

Rabbit anti Bovine

E61I02501 EnoGene 0.1mg 411.6 EUR

Anti-Rabbit antibody

STJ11100323 St John's Laboratory 100 µl 332.4 EUR

Mouse anti Rabbit IgG

40-1005 Fitzgerald 1 mg 418.8 EUR

Mouse anti Rabbit IgG

40-1006 Fitzgerald 1 mg 418.8 EUR

Rabbit anti Chicken IgG

41C-CB0315 Fitzgerald 2 mg 322.8 EUR

Rabbit anti Goat IgG

41C-CB0529 Fitzgerald 2 mg 292.8 EUR

Goat anti Rabbit IgG

41C-CB1143 Fitzgerald 2 mg 333.6 EUR

Goat anti Rabbit IgG

41C-CB1150 Fitzgerald 10 mg 465.6 EUR

Rabbit anti Mouse IgG1

41C-CB5120 Fitzgerald 1 mg 373.2 EUR

Rabbit anti Mouse IgG2a

41C-CB5127 Fitzgerald 1 mg 373.2 EUR

Rabbit anti Mouse IgA

41C-CB5143 Fitzgerald 1 mg 432 EUR

Goat anti Rabbit IgG

41R-1079 Fitzgerald 2 mg 178.8 EUR

Rabbit anti Bovine IgA

41R-RB001 Fitzgerald 1 mg 259.2 EUR
Biomarkers were sharply increased or decreased in rabbits pretreated with c-IgG, but not those pretreated with MEDI3902, including ratio of arterial oxygen partial pressure to fractional inspired oxygen PaO2/FiO2 <300, hypercapnia or hypocapnia, severe lactic acidosis, leukopenia and neutropenia.
Cytokines and chemokines associated with ARDS were significantly downregulated in lungs from rabbits pretreated with MEDI3902 compared with c-IgG.
These results suggest that MEDI3902 prophylaxis could have potential clinical utility for decreasing severity of P. aeruginosa ventilator-associated pneumonia.

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